Post-acute Sequelae of SARS-CoV-2 Infection, Long COVID
Conditions
Brief summary
The purpose of this study is to compare whether being treated with nirmatrelvir plus ritonavir for 15 days works better than being treated with placebo plus ritonavir to reduce severe symptoms of Long Covid. Participants will have 5 planned visits to the study clinic over 15 weeks and will take the drug (or placebo) for the first 15 days. This study uses the term post-acute sequelae of SARS-CoV-2 (PASC), which is another name for Long Covid.
Detailed description
An exploratory sub-study will investigate the correlation of physical activity and biometric parameters from digital wearable devices with the subjective symptom severity and other patient-reported outcomes in the main study. All participants with iPhone 6S Plus or newer will be offered an opportunity to opt-in to this sub-study. An Apple Watch and Bluetooth-enabled blood pressure monitor will be provided to participants and data will be collected for the duration of the main study to track participants' physiological and behavioral trends in the Paxlovid versus placebo groups.
Interventions
DRUGNirmatrelvir
Two 150 mg tablets taken by mouth every 12 hours
DRUGPlacebo
Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours
DRUGRitonavir
One 100 mg capsule taken by mouth every 12 hours
Sponsors
Pfizer
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Normal or near-normal kidney function * History of confirmed COVID-19 infection that preceded the post-COVID symptoms * Post-COVID-19 symptoms persisting greater than three months * At least 2 post-COVID symptoms of moderate or severe intensity (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, or cardiovascular symptoms) * Willing to report all vaccinations * Women of childbearing potential or men whose partners may become pregnant must use acceptable method of contraception during the treatment period and for 28 days after the last dose of the study drug * Willing and able to adhere to study procedures and available for the duration of the study
Exclusion criteria
* Suspected or confirmed pregnancy or breastfeeding * Severe liver disease * Prior use of study drug or other COVID treatment within 30 days * Hypersensitivity or other contraindication to any components of the study drug * Current or expected use of any medication dependent on or inducer of CYP3A4 * Current or expected use of supplements or herbs (unless medically necessary) that cannot be temporarily held (period as determined necessary by investigators) * HIV infection with viral load \>50 copies/ml * Suspected or confirmed active COVID infection within 30 days * History of COVID vaccine within 28 days prior to enrollment, or other vaccine (influenza, shingles, etc.) within 14 days of enrollment, or planned use of any vaccine until the primary endpoint has been met (10 weeks) * Other medical condition(s) or concomitant therapy that would compromise participant's safety or compliance with the study protocol or significantly confound interpretation of study results, as determined by study investigators * Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device * Inability to provide informed consent * Currently hospitalized
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Week 10 | This measure was to evaluate whether there is a difference between treatment with Paxlovid versus placebo on any of the 6 core symptoms of PASC at week 10 (adjusting for patients' baseline levels). Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks | Baseline through week 10, assessed at week 10 | Relief defined as reduction of severity from moderate to none, or severe to mild/none (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms. |
| Number of Participants With Overall Alleviation for 2 Weeks | Baseline through week 10, assessed at week 10 | Overall alleviation defined as both: 1. Any core symptom(s) that are none/mild (Likert 0 or 1) at baseline are none at 10 weeks, and 2. Any core symptom(s) that are moderate/severe (Likert 2 or 3) at baseline are none/mild at 10 weeks. Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms. |
| Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Assessed at weeks 5, 10, and 15 | This outcome was to assess the severity of the most bothersome symptom experienced by participants. Each symptom was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms) using the Core Symptoms Severity Scale. |
| Time to Relief of the 6 Core Symptoms | Up to 15 weeks | Relief defined as reduction of severity from moderate to none, or severe to mild/none for 2 consecutive weeks (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms. |
| Time to Relief of the Most Bothersome Symptom | Up to 15 weeks | Relief defined as reduction of severity from moderate to none, or severe to mild/none for 2 consecutive weeks (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms. |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score | Baseline and week 10 | The PROMIS-Physical Function Short Form (SF) assesses difficulty level performing activities of daily living such as doing chores, climbing stairs, walking, and running errands. The assessment consists of 4 items (questions) with each item scored on 5-point Likert scale (higher scores correspond to better physical function). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher physical function T-score indicates better physical function. |
| Change in PROMIS Fatigue T-Score | Baseline and week 10 | The PROMIS Fatigue Score assesses level of fatigue and its interference on daily activities. The assessment consists of 7 items (questions) with each item scored on 5-point Likert scale (higher scores correspond to more fatigue). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher fatigue T-score indicates greater fatigue. |
| Change in PROMIS Dyspnea-Severity T-Score | Baseline and week 10 | The PROMIS-Fatigue Dyspnea-Severity Short Form assesses shortness of breath and its interference on daily activities. The assessment consists of 5 items (questions) scored on 4-point Likert scale with a 7-day recall period (higher scores correspond to worse symptoms). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher Dyspnea-Severity T-score indicates worse symptoms. |
| Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Day 15 | This measure was to evaluate whether there is a difference between treatment with Paxlovid versus placebo on any of the 6 core symptoms of PASC at week 10 (adjusting for patients' baseline levels). Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). |
| Change in Orthostatic Vitals Test | Baseline and week 10 | This outcome measures the difference in supine to standing systolic blood pressure (SBP) and diastolic blood pressure (DBP). |
| Change in Heart Rate | Baseline and week 10 | This outcome measures the difference in supine to standing heart rate. |
| Change in 1-minute Sit-to-stand Test | Baseline and week 10 | Number of times participant is able to go from sitting (in an armless chair) to standing in 1 minute (sit to stand cycles). |
| Patient Global Impression of Severity (PGIS) Scale Score | Day 15, and weeks 5, 10, and 15 | The PGIS reflects a participant's perception about the overall severity of their disease symptoms, rated from 1 to 6 (1 = not present; 2 = very mild; 3 = mild; 4 = moderate; 5 = severe; 6 = extremely severe). |
| Patient Global Impression of Change (PGIC) Scale Score | Day 15, and weeks 5, 10, and 15 | The PGIC reflects a participant's perception about the overall efficacy of treatment and their overall status since the start of the treatment, rated from 1 to 7 (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse). |
| Summative Severity Score for All Core Symptoms | Weeks 5, 10, and 15 | Core Symptoms Severity Scale Scores for each of the 6 core symptoms were summed to create a summative score. Each core symptom is assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). Summative score range: 0 to 18 (high scores correspond to greater severity). |
| Percentage of Weeks 1-15 With Mild or no Symptoms | 15 weeks | Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) is assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). |
| Change in PROMIS Cognitive Function Abilities T-Score | Baseline and week 10 | The PROMIS-Cognitive Function Abilities Short Form assesses brain fog and its interference on daily activities. The assessment consists of 4 items scored on 5-point Likert scale with a 7-day recall period (higher scores indicate better cognitive function). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher Cognitive Function T-score indicates better cognitive function. |
Countries
United States
Participant flow
Pre-assignment details
168 participants were consented and screened. 155 participants were randomized to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Nirmatrelvir Plus Ritonavir Participants receive nirmatrelvir (two 150 mg tablets) plus ritonavir (one 100 mg capsule) every 12 hours for 15 days, and attend follow-up visits through week 15. | 102 |
| Placebo Plus Ritonavir Participants receive placebo to match nirmatrelvir plus ritonavir (one 100 mg capsule) every 12 hours for 15 days, and attend follow-up visits through week 15. | 53 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to follow-up within 15-day treatment period | 2 | 0 |
| Overall Study | Requested to withdraw after 15-day treatment period | 2 | 2 |
| Overall Study | Requested to withdraw within 15-day treatment period | 0 | 1 |
| Overall Study | Withdrawn by site within 15-day treatment period | 0 | 1 |
Baseline characteristics
| Characteristic | Nirmatrelvir Plus Ritonavir | Placebo Plus Ritonavir | Total |
|---|---|---|---|
| Age, Continuous | 44.5 years | 41 years | 43 years |
| BMI group Normal (18.5-24.9) | 39 Participants | 17 Participants | 56 Participants |
| BMI group Obesity (≥30.0) | 26 Participants | 18 Participants | 44 Participants |
| BMI group Overweight (25.0-29.9) | 33 Participants | 18 Participants | 51 Participants |
| BMI group Underweight (<18.5) | 4 Participants | 0 Participants | 4 Participants |
| Body Mass Index (BMI) | 27 kg/m^2 STANDARD_DEVIATION 6.19 | 28 kg/m^2 STANDARD_DEVIATION 6.66 | 27.55 kg/m^2 STANDARD_DEVIATION 6.36 |
| Comorbidities Allergies | 1 Participants | 12 Participants | 13 Participants |
| Comorbidities Anxiety | 15 Participants | 8 Participants | 23 Participants |
| Comorbidities Asthma | 15 Participants | 13 Participants | 28 Participants |
| Comorbidities Depression | 24 Participants | 13 Participants | 37 Participants |
| Comorbidities Gastroesophageal reflux disease (GERD) | 15 Participants | 6 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 7 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 46 Participants | 136 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hospitalized for index COVID-19 infection | 6 Participants | 3 Participants | 9 Participants |
| Index COVID-19 infection date After December 2021 | 43 Participants | 24 Participants | 67 Participants |
| Index COVID-19 infection date Before May 2021 | 39 Participants | 22 Participants | 61 Participants |
| Index COVID-19 infection date May to December 2021 | 20 Participants | 7 Participants | 27 Participants |
| Moderate to severe post-COVID-19 symptoms 2-3 symptoms | 47 Participants | 25 Participants | 72 Participants |
| Moderate to severe post-COVID-19 symptoms >3 symptoms | 55 Participants | 28 Participants | 83 Participants |
| Moderate to severe symptom at baseline Body aches | 59 Participants | 27 Participants | 86 Participants |
| Moderate to severe symptom at baseline Brain fog | 83 Participants | 42 Participants | 125 Participants |
| Moderate to severe symptom at baseline Cardiovascular | 50 Participants | 32 Participants | 82 Participants |
| Moderate to severe symptom at baseline Fatigue | 97 Participants | 51 Participants | 148 Participants |
| Moderate to severe symptom at baseline Gastrointestinal | 42 Participants | 25 Participants | 67 Participants |
| Moderate to severe symptom at baseline Shortness of breath | 47 Participants | 28 Participants | 75 Participants |
| Prior use of SARS-CoV-2 acute medication No prior use | 75 Participants | 39 Participants | 114 Participants |
| Prior use of SARS-CoV-2 acute medication Prior use of medication other than Paxlovid | 27 Participants | 14 Participants | 41 Participants |
| Prior use of SARS-CoV-2 acute medication Prior use of Paxlovid | 18 Participants | 9 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 9 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 76 Participants | 39 Participants | 115 Participants |
| Region of Enrollment United States | 102 Participants | 53 Participants | 155 Participants |
| Sex: Female, Male Female | 61 Participants | 31 Participants | 92 Participants |
| Sex: Female, Male Male | 41 Participants | 22 Participants | 63 Participants |
| Time from index infection to randomization | 17.6 months STANDARD_DEVIATION 9.1 | 17.3 months STANDARD_DEVIATION 9.1 | 17.5 months STANDARD_DEVIATION 9.1 |
| Total COVID-19 infections | 1.45 infections STANDARD_DEVIATION 0.75 | 1.34 infections STANDARD_DEVIATION 0.55 | 1.41 infections STANDARD_DEVIATION 0.69 |
| Vaccination status at randomization Initial series completed | 101 Participants | 52 Participants | 153 Participants |
| Vaccination status at randomization Initial series not completed | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 53 |
| other Total, other adverse events | 100 / 102 | 48 / 53 |
| serious Total, serious adverse events | 3 / 102 | 1 / 53 |
Outcome results
Primary
Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score
This measure was to evaluate whether there is a difference between treatment with Paxlovid versus placebo on any of the 6 core symptoms of PASC at week 10 (adjusting for patients' baseline levels). Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).
Time frame: Week 10
Population: If participants did not have week 10 data, week 9 data were used when available; otherwise missing data were imputed for statistical analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - moderate symptoms | 43 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - mild symptoms | 32 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - severe symptoms | 19 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - moderate symptoms | 21 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - no symptoms | 11 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - severe symptoms | 15 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - no symptoms | 42 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - no symptoms | 38 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - mild symptoms | 22 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - mild symptoms | 39 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - mild symptoms | 31 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - moderate symptoms | 17 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - mild symptoms | 34 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - severe symptoms | 5 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - moderate symptoms | 22 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - no symptoms | 37 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - severe symptoms | 31 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - mild symptoms | 35 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - severe symptoms | 4 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - moderate symptoms | 20 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - moderate symptoms | 35 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - severe symptoms | 7 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - no symptoms | 31 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Missing Core Symptoms Severity data at week 10 | 3 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - no symptoms | 3 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Missing Core Symptoms Severity data at week 10 | 4 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - no symptoms | 4 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - mild symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - moderate symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Fatigue - severe symptoms | 11 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - no symptoms | 8 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - mild symptoms | 24 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - moderate symptoms | 12 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Brain fog - severe symptoms | 5 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - no symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - mild symptoms | 21 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - moderate symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Dyspnea - severe symptoms | 2 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - no symptoms | 15 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - mild symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - moderate symptoms | 14 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Body aches - severe symptoms | 3 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - no symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - mild symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - moderate symptoms | 16 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - severe symptoms | 3 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - no symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - mild symptoms | 11 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - moderate symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - severe symptoms | 8 Participants |
Comparison: A proportional odds logistic regression model was fit for severity of each core symptom at week 10, adjusting for baseline severity of the corresponding symptom and fit using only those who experienced the symptom at baseline. A test statistic for overall efficacy was calculated as the weighted average of the treatment coefficient in the proportional odds model for each symptom with inverse variance weighting. The p-value was obtained by a nonparametric permutation test.p-value: 0.903Nonparametric permutation test
Secondary
Change in 1-minute Sit-to-stand Test
Number of times participant is able to go from sitting (in an armless chair) to standing in 1 minute (sit to stand cycles).
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in 1-minute Sit-to-stand Test | Baseline | 20.48 cycles | Standard Deviation 10.69 |
| Nirmatrelvir Plus Ritonavir | Change in 1-minute Sit-to-stand Test | Change at week 10 | 2.67 cycles | Standard Deviation 10.8 |
| Placebo Plus Ritonavir | Change in 1-minute Sit-to-stand Test | Baseline | 20.51 cycles | Standard Deviation 9.8 |
| Placebo Plus Ritonavir | Change in 1-minute Sit-to-stand Test | Change at week 10 | 3.27 cycles | Standard Deviation 7.25 |
p-value: 0.83395% CI: [-4.24, 3.42]Regression, Linear
Secondary
Change in Heart Rate
This outcome measures the difference in supine to standing heart rate.
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in Heart Rate | Baseline | 6.22 bpm | Standard Deviation 11.92 |
| Nirmatrelvir Plus Ritonavir | Change in Heart Rate | Change at week 10 | 0.878 bpm | Standard Deviation 14.2 |
| Placebo Plus Ritonavir | Change in Heart Rate | Change at week 10 | 1.4 bpm | Standard Deviation 11.5 |
| Placebo Plus Ritonavir | Change in Heart Rate | Baseline | 7.70 bpm | Standard Deviation 8.39 |
p-value: 0.85695% CI: [-6.15, 5.12]Regression, Linear
Secondary
Change in Orthostatic Vitals Test
This outcome measures the difference in supine to standing systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in Orthostatic Vitals Test | SBP - change at week 10 | -2.86 mmHg | Standard Deviation 15.9 |
| Nirmatrelvir Plus Ritonavir | Change in Orthostatic Vitals Test | DBP - change at week 10 | -1.86 mmHg | Standard Deviation 1.9 |
| Nirmatrelvir Plus Ritonavir | Change in Orthostatic Vitals Test | DBP - baseline | 6.26 mmHg | Standard Deviation 8.36 |
| Nirmatrelvir Plus Ritonavir | Change in Orthostatic Vitals Test | SBP - baseline | 1.79 mmHg | Standard Deviation 12.52 |
| Placebo Plus Ritonavir | Change in Orthostatic Vitals Test | DBP - baseline | 6.43 mmHg | Standard Deviation 10.9 |
| Placebo Plus Ritonavir | Change in Orthostatic Vitals Test | SBP - change at week 10 | -4.47 mmHg | Standard Deviation 14.1 |
| Placebo Plus Ritonavir | Change in Orthostatic Vitals Test | SBP - baseline | 3.77 mmHg | Standard Deviation 12.15 |
| Placebo Plus Ritonavir | Change in Orthostatic Vitals Test | DBP - change at week 10 | -1.51 mmHg | Standard Deviation 13.7 |
Comparison: Analysis of data for change of systolic blood pressurep-value: 0.55595% CI: [-4.06, 7.53]Regression, Linear
Comparison: Analysis of data for change of diastolic blood pressurep-value: 0.76495% CI: [-5.15, 3.79]Regression, Linear
Secondary
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score
The PROMIS-Physical Function Short Form (SF) assesses difficulty level performing activities of daily living such as doing chores, climbing stairs, walking, and running errands. The assessment consists of 4 items (questions) with each item scored on 5-point Likert scale (higher scores correspond to better physical function). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher physical function T-score indicates better physical function.
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score | Baseline | 37.97 T-score | Standard Deviation 6.26 |
| Nirmatrelvir Plus Ritonavir | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score | Change at week 10 | 2.73 T-score | Standard Deviation 6.62 |
| Placebo Plus Ritonavir | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score | Baseline | 38.98 T-score | Standard Deviation 8.71 |
| Placebo Plus Ritonavir | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score | Change at week 10 | 1.32 T-score | Standard Deviation 5.75 |
p-value: 0.6695% CI: [-1.96, 3.1]Regression, Linear
Secondary
Change in PROMIS Cognitive Function Abilities T-Score
The PROMIS-Cognitive Function Abilities Short Form assesses brain fog and its interference on daily activities. The assessment consists of 4 items scored on 5-point Likert scale with a 7-day recall period (higher scores indicate better cognitive function). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher Cognitive Function T-score indicates better cognitive function.
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in PROMIS Cognitive Function Abilities T-Score | Baseline | 35.78 T-score | Standard Deviation 7.9 |
| Nirmatrelvir Plus Ritonavir | Change in PROMIS Cognitive Function Abilities T-Score | Change at week 10 | 4.84 T-score | Standard Deviation 8.18 |
| Placebo Plus Ritonavir | Change in PROMIS Cognitive Function Abilities T-Score | Baseline | 39.09 T-score | Standard Deviation 6.84 |
| Placebo Plus Ritonavir | Change in PROMIS Cognitive Function Abilities T-Score | Change at week 10 | 5.05 T-score | Standard Deviation 7.56 |
p-value: 0.9895% CI: [-3.21, 3.28]Regression, Linear
Secondary
Change in PROMIS Dyspnea-Severity T-Score
The PROMIS-Fatigue Dyspnea-Severity Short Form assesses shortness of breath and its interference on daily activities. The assessment consists of 5 items (questions) scored on 4-point Likert scale with a 7-day recall period (higher scores correspond to worse symptoms). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher Dyspnea-Severity T-score indicates worse symptoms.
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in PROMIS Dyspnea-Severity T-Score | Baseline | 52.18 T-score | Standard Deviation 7.49 |
| Nirmatrelvir Plus Ritonavir | Change in PROMIS Dyspnea-Severity T-Score | Change at week 10 | -1.96 T-score | Standard Deviation 7.9 |
| Placebo Plus Ritonavir | Change in PROMIS Dyspnea-Severity T-Score | Baseline | 52.59 T-score | Standard Deviation 8.67 |
| Placebo Plus Ritonavir | Change in PROMIS Dyspnea-Severity T-Score | Change at week 10 | -2.38 T-score | Standard Deviation 6.13 |
p-value: 0.795% CI: [-2.55, 3.75]Regression, Linear
Secondary
Change in PROMIS Fatigue T-Score
The PROMIS Fatigue Score assesses level of fatigue and its interference on daily activities. The assessment consists of 7 items (questions) with each item scored on 5-point Likert scale (higher scores correspond to more fatigue). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher fatigue T-score indicates greater fatigue.
Time frame: Baseline and week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Change in PROMIS Fatigue T-Score | Baseline | 66.00 T-score | Standard Deviation 6.42 |
| Nirmatrelvir Plus Ritonavir | Change in PROMIS Fatigue T-Score | Change at week 10 | -3.92 T-score | Standard Deviation 7.88 |
| Placebo Plus Ritonavir | Change in PROMIS Fatigue T-Score | Baseline | 64.00 T-score | Standard Deviation 6.45 |
| Placebo Plus Ritonavir | Change in PROMIS Fatigue T-Score | Change at week 10 | -4.05 T-score | Standard Deviation 5.9 |
p-value: 0.7995% CI: [-2.4, 3.15]Regression, Linear
Secondary
Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks
Relief defined as reduction of severity from moderate to none, or severe to mild/none (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.
Time frame: Baseline through week 10, assessed at week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir Plus Ritonavir | Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks | 33 Participants |
| Placebo Plus Ritonavir | Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks | 22 Participants |
p-value: 0.0995% CI: [0.27, 1.09]Regression, Logistic
Secondary
Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score
This measure was to evaluate whether there is a difference between treatment with Paxlovid versus placebo on any of the 6 core symptoms of PASC at week 10 (adjusting for patients' baseline levels). Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).
Time frame: Day 15
Population: Participants with symptoms data at day 15
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - moderate symptoms | 34 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - mild symptoms | 17 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - moderate symptoms | 43 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - severe symptoms | 36 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - no symptoms | 7 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - mild symptoms | 36 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - no symptoms | 3 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - severe symptoms | 22 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - no symptoms | 31 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - mild symptoms | 40 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - moderate symptoms | 22 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - severe symptoms | 6 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - no symptoms | 21 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - mild symptoms | 35 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - moderate symptoms | 31 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - severe symptoms | 12 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - no symptoms | 24 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - mild symptoms | 27 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - moderate symptoms | 35 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - severe symptoms | 13 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - no symptoms | 29 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - mild symptoms | 34 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - moderate symptoms | 28 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - severe symptoms | 8 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - moderate symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - no symptoms | 3 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - no symptoms | 16 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - mild symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - moderate symptoms | 18 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - moderate symptoms | 16 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - mild symptoms | 15 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Fatigue - severe symptoms | 16 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - mild symptoms | 12 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - no symptoms | 2 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - moderate symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - mild symptoms | 19 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - severe symptoms | 4 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - moderate symptoms | 18 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Body aches - severe symptoms | 4 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Brain fog - severe symptoms | 9 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - severe symptoms | 10 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - no symptoms | 12 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - no symptoms | 12 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - mild symptoms | 20 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Cardiovascular symptoms - no symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - moderate symptoms | 12 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Gastrointestinal symptoms - mild symptoms | 14 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score | Dyspnea - severe symptoms | 4 Participants |
Comparison: Analysis of fatigue score at day 15p-value: 0.17495% CI: [0.82, 2.94]Regression, odds
Comparison: Analysis of brain fog score at day 15p-value: 0.54895% CI: [0.65, 2.25]Regression, odds
Comparison: Analysis of dyspnea score at day 15p-value: 0.13495% CI: [0.33, 1.16]Regression, odds
Comparison: Analysis of body aches score at day 15p-value: 0.24195% CI: [0.78, 2.69]Regression, odds
Comparison: Analysis of gastrointestinal symptoms score at day 15p-value: 0.92295% CI: [0.55, 1.92]Regression, odds
Comparison: Analysis of cardiovascular symptoms score at day 15p-value: 0.03295% CI: [0.26, 0.94]Regression, odds
Secondary
Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom
This outcome was to assess the severity of the most bothersome symptom experienced by participants. Each symptom was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms) using the Core Symptoms Severity Scale.
Time frame: Assessed at weeks 5, 10, and 15
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to the respective data collection time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Missing symptoms data at week 5 | 10 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - severe symptoms | 39 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - mild symptoms | 17 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Missing symptoms data at week 10 | 4 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - no symptoms | 3 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - no symptoms | 2 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - severe symptoms | 34 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - mild symptoms | 27 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - mild symptoms | 22 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - moderate symptoms | 32 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - moderate symptoms | 41 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - severe symptoms | 37 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - moderate symptoms | 34 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Missing symptoms data at week 15 | 4 Participants |
| Nirmatrelvir Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - no symptoms | 0 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Missing symptoms data at week 15 | 6 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - no symptoms | 1 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - mild symptoms | 12 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - moderate symptoms | 18 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 5 - severe symptoms | 13 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Missing symptoms data at week 5 | 9 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - no symptoms | 2 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - mild symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - moderate symptoms | 18 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 10 - severe symptoms | 11 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Missing symptoms data at week 10 | 5 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - no symptoms | 3 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - mild symptoms | 20 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - moderate symptoms | 17 Participants |
| Placebo Plus Ritonavir | Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom | Week 15 - severe symptoms | 7 Participants |
Comparison: Analysis of severity at week 5p-value: 0.15695% CI: [0.83, 3.15]Regression, odds
Comparison: Analysis of severity at week 10p-value: 0.0395% CI: [1.06, 3.72]Regression, odds
Comparison: Analysis of severity at week 15p-value: 0.0195% CI: [1.27, 4.6]Regression, odds
Secondary
Number of Participants With Overall Alleviation for 2 Weeks
Overall alleviation defined as both: 1. Any core symptom(s) that are none/mild (Likert 0 or 1) at baseline are none at 10 weeks, and 2. Any core symptom(s) that are moderate/severe (Likert 2 or 3) at baseline are none/mild at 10 weeks. Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.
Time frame: Baseline through week 10, assessed at week 10
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 10
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir Plus Ritonavir | Number of Participants With Overall Alleviation for 2 Weeks | 7 Participants |
| Placebo Plus Ritonavir | Number of Participants With Overall Alleviation for 2 Weeks | 5 Participants |
p-value: 0.695% CI: [0.21, 2.44]Regression, Linear
Secondary
Patient Global Impression of Change (PGIC) Scale Score
The PGIC reflects a participant's perception about the overall efficacy of treatment and their overall status since the start of the treatment, rated from 1 to 7 (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse).
Time frame: Day 15, and weeks 5, 10, and 15
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to the respective data collection time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Day 15 | 3.74 score on a scale | Standard Deviation 1.22 |
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Week 5 | 3.52 score on a scale | Standard Deviation 1.29 |
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Week 10 | 3.38 score on a scale | Standard Deviation 1.31 |
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Week 15 | 3.38 score on a scale | Standard Deviation 1.42 |
| Placebo Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Week 15 | 3.09 score on a scale | Standard Deviation 1.1 |
| Placebo Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Day 15 | 3.51 score on a scale | Standard Deviation 1.08 |
| Placebo Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Week 10 | 3.13 score on a scale | Standard Deviation 1.03 |
| Placebo Plus Ritonavir | Patient Global Impression of Change (PGIC) Scale Score | Week 5 | 3.59 score on a scale | Standard Deviation 1.13 |
Comparison: Analysis of day 15 datap-value: 0.44495% CI: [-0.3, 0.67]Regression, Linear
Comparison: Analysis of week 5 datap-value: 0.34695% CI: [-0.78, 0.28]Regression, Linear
Comparison: Analysis of week 10 datap-value: 0.73895% CI: [-0.48, 0.67]Regression, Linear
Comparison: Analysis of week 15 datap-value: 0.57895% CI: [-0.43, 0.76]Regression, Linear
Secondary
Patient Global Impression of Severity (PGIS) Scale Score
The PGIS reflects a participant's perception about the overall severity of their disease symptoms, rated from 1 to 6 (1 = not present; 2 = very mild; 3 = mild; 4 = moderate; 5 = severe; 6 = extremely severe).
Time frame: Day 15, and weeks 5, 10, and 15
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to the respective data collection time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Week 5 | 4.01 score on a scale | Standard Deviation 0.99 |
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Week 15 | 3.94 score on a scale | Standard Deviation 1.03 |
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Week 10 | 4.00 score on a scale | Standard Deviation 1.03 |
| Nirmatrelvir Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Day 15 | 4.04 score on a scale | Standard Deviation 0.98 |
| Placebo Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Week 10 | 3.79 score on a scale | Standard Deviation 1.06 |
| Placebo Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Week 5 | 3.73 score on a scale | Standard Deviation 1.02 |
| Placebo Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Day 15 | 3.72 score on a scale | Standard Deviation 1.02 |
| Placebo Plus Ritonavir | Patient Global Impression of Severity (PGIS) Scale Score | Week 15 | 3.62 score on a scale | Standard Deviation 1.07 |
Comparison: Analysis of day 15 datap-value: 0.09695% CI: [-0.06, 0.7]Regression, Linear
Comparison: Analysis of week 5 datap-value: 0.29395% CI: [-0.2, 0.64]Regression, Linear
Comparison: Analysis of week 10 datap-value: 0.39695% CI: [-0.25, 0.62]Regression, Linear
Comparison: Analysis of week 15 datap-value: 0.06495% CI: [-0.02, 0.77]Regression, Linear
Secondary
Percentage of Weeks 1-15 With Mild or no Symptoms
Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) is assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).
Time frame: 15 weeks
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to week 15.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Fatigue | 0.15 percentage of weeks |
| Nirmatrelvir Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Brain fog | 0.31 percentage of weeks |
| Nirmatrelvir Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Body Aches | 0.54 percentage of weeks |
| Nirmatrelvir Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Cardiovascular symptoms | 0.67 percentage of weeks |
| Nirmatrelvir Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Shortness of breath | 0.769 percentage of weeks |
| Nirmatrelvir Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Gastrointestinal symptoms | 0.63 percentage of weeks |
| Placebo Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Shortness of breath | 0.62 percentage of weeks |
| Placebo Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Fatigue | 0.15 percentage of weeks |
| Placebo Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Cardiovascular symptoms | 0.46 percentage of weeks |
| Placebo Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Brain fog | 0.56 percentage of weeks |
| Placebo Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Gastrointestinal symptoms | 0.52 percentage of weeks |
| Placebo Plus Ritonavir | Percentage of Weeks 1-15 With Mild or no Symptoms | Body Aches | 0.64 percentage of weeks |
Comparison: Post-hoc analysis of fatigue datap-value: 0.0295% CI: [0.33, 0.92]Regression, Logistic
Comparison: Post-hoc analysis of brain fog datap-value: 0.0195% CI: [0.31, 0.82]Regression, Logistic
Comparison: Post-hoc analysis of body aches datap-value: 0.3495% CI: [0.74, 2.33]Regression, Logistic
Comparison: Post-hoc analysis of cardiovascular symptoms datap-value: 0.2995% CI: [0.76, 2.48]Regression, Logistic
Comparison: Post-hoc analysis of shortness of breath datap-value: 0.3595% CI: [0.73, 2.38]Regression, Logistic
Comparison: Post-hoc analysis of gastrointestinal symptoms datap-value: 0.2595% CI: [0.79, 2.47]Regression, Logistic
Secondary
Summative Severity Score for All Core Symptoms
Core Symptoms Severity Scale Scores for each of the 6 core symptoms were summed to create a summative score. Each core symptom is assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). Summative score range: 0 to 18 (high scores correspond to greater severity).
Time frame: Weeks 5, 10, and 15
Population: Missing data were imputed for statistical analysis, including for participants who were withdrawn prior to the respective data collection time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Summative Severity Score for All Core Symptoms | Week 5 | 8.40 score on a scale | Standard Deviation 3.56 |
| Nirmatrelvir Plus Ritonavir | Summative Severity Score for All Core Symptoms | Week 10 | 7.62 score on a scale | Standard Deviation 3.75 |
| Nirmatrelvir Plus Ritonavir | Summative Severity Score for All Core Symptoms | Week 15 | 7.90 score on a scale | Standard Deviation 3.8 |
| Placebo Plus Ritonavir | Summative Severity Score for All Core Symptoms | Week 5 | 8.20 score on a scale | Standard Deviation 3.88 |
| Placebo Plus Ritonavir | Summative Severity Score for All Core Symptoms | Week 10 | 7.69 score on a scale | Standard Deviation 4.09 |
| Placebo Plus Ritonavir | Summative Severity Score for All Core Symptoms | Week 15 | 7.09 score on a scale | Standard Deviation 4.15 |
Comparison: Analysis of week 5 datap-value: 0.75895% CI: [-1.41, 1.03]Regression, Linear
Comparison: Analysis of week 10 datap-value: 0.69395% CI: [-1.46, 0.97]Regression, Linear
Comparison: Analysis of week 15 datap-value: 0.55895% CI: [-0.87, 1.61]Regression, Linear
Secondary
Time to Relief of the 6 Core Symptoms
Relief defined as reduction of severity from moderate to none, or severe to mild/none for 2 consecutive weeks (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.
Time frame: Up to 15 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nirmatrelvir Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Fatigue | 15 weeks |
| Nirmatrelvir Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Brain fog | 15 weeks |
| Nirmatrelvir Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Body aches | 15 weeks |
| Nirmatrelvir Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Cardiovascular symptoms | 15 weeks |
| Nirmatrelvir Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Shortness of breath | 15 weeks |
| Nirmatrelvir Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Gastrointestinal symptoms | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Shortness of breath | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Fatigue | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Cardiovascular symptoms | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Brain fog | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Gastrointestinal symptoms | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the 6 Core Symptoms | Body aches | 15 weeks |
Comparison: Analysis of data for Time to relief - fatiguep-value: 0.74495% CI: [0.45, 1.77]Cox PH coefficient Wald test
Comparison: Analysis of data for Time to relief - brain fogp-value: 0.25995% CI: [0.32, 1.37]Cox PH coefficient Wald test
Comparison: Analysis of data for Time to relief - body achesp-value: 0.28695% CI: [0.65, 3.99]Cox PH coefficient Wald test
Comparison: Analysis of data for Time to relief - cardiovascular symptomsp-value: 0.84695% CI: [0.38, 2.24]Cox PH coefficient Wald test
Comparison: Analysis of data for Time to relief - shortness of breathp-value: 0.4195% CI: [0.51, 4.73]Cox PH coefficient Wald test
Comparison: Analysis of data for Time to relief - gastrointestinal symptomsp-value: 0.8895% CI: [0.42, 2.11]Cox PH coefficient Wald test
Secondary
Time to Relief of the Most Bothersome Symptom
Relief defined as reduction of severity from moderate to none, or severe to mild/none for 2 consecutive weeks (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.
Time frame: Up to 15 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nirmatrelvir Plus Ritonavir | Time to Relief of the Most Bothersome Symptom | 15 weeks |
| Placebo Plus Ritonavir | Time to Relief of the Most Bothersome Symptom | 15 weeks |
p-value: 0.3395% CI: [0.4, 1.38]Cox PH coefficient Wald test