COVID-19
Conditions
Keywords
Coronavirus
Brief summary
Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
Detailed description
We will conduct an investigator-initiated, multicenter, blinded, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo for early treatment of adults with COVID-19 in the outpatient setting prior to hospitalization. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Interventions
DRUGLopinavir/Ritonavir 400 mg/100 mg
Lopinavir/Ritonavir tablets
OTHERPlacebo
Unmatched placebo
Sponsors
AbbVie
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Lopinavir/Ritonavir tablets or unmatched placebo tablets
Intervention model description
Blinded, multicenter, placebo-controlled randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcription polymerase chain reaction (RT-PCR) or other molecular test collected within the past 6 days 3. Current symptoms of acute respiratory infection for ≤6 days, defined as one or more of the following: cough, fever, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, body aches, weakness/fatigue.
Exclusion criteria
1. Prisoner 2. Pregnancy 3. Breast feeding 4. Two individuals from the same household are not enrolled in the study 5. Unable to randomize within 6 days after onset of acute respiratory infection symptoms 6. Hospitalization within the 6 days prior to randomization 7. Inability to swallow oral medications 8. Refusal or inability to be contacted and participate in daily symptom/safety monitoring in English or Spanish during the two-week follow-up period 9. Previous enrollment in this trial 10. Known severe chronic kidney disease requiring dialysis 11. Known severe liver disease \[cirrhosis or \>3 times upper limit of normal for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in medical record if available\] 12. Known hepatitis B or hepatitis C infection 13. Known history of jaundice 14. Current heavy alcohol use, defined as 8 drinks or more per week for women or 15 drinks or more per week for men 15. Known seizure disorder 16. Known human immunodeficiency virus (HIV) infection 17. Known history of pancreatitis 18. Known history of prolonged QT interval \[Long QT Syndrome, patient report, or corrected QT interval (QTc) \>500 milliseconds on most recently available electrocardiogram within the past 2 years\] 19. Receipt of \>1 dose of lopinavir/ritonavir in the 10 days prior to enrollment 20. Known allergy to lopinavir/ritonavir 21. Currently prescribed (with planned continuation) or planned administration during 14-day study period of medication at high risk for QT prolongation as follows: Antiarrhythmics: Amiodarone, disopyramide, dofetilide, dronedarone, flecainide, ibutilide, procainamide, propafenone, quinidine, sotalol Anti-cancer: Arsenic trioxide, oxaliplatin, vandetanib Antidepressants: Amitriptyline, citalopram, escitalopram, imipramine Antimicrobials: azithromycin, ciprofloxacin, clarithromycin, erythromycin, fluconazole, levofloxacin, moxifloxacin, pentamidine, hydroxychloroquine Antipsychotics: haloperidol, chlorpromazine, droperidol, olanzapine, pimozide, quetiapine, thioridazine, risperidone, ziprasidone Others: cilostazol, cimetidine, cisapride, donepezil, methadone, ondansetron, sumatriptan 22. Currently prescribed (with planned continuation) or planned administration during 14-day study period of any of the following medications: alfuzosin, apalutamide, astemizole, ergot-containing medicines (including dihydroergotamine mesylate, ergotamine tartrate, methylergonovine), lomitapide, lovastatin, lurasidone, midazolam, phenobarbital, phenytoin, ranolazine, rifampin, sildenafil, simvastatin, St. John's Wort, terfenadine, triazolam. Patients who are on warfarin or fluticasone will be advised to contact their primary care provider to advise them that they are in the trial and possibly receiving lopinavir/ritonavir which can influence levels of either drug and may require more frequent monitoring.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Day 1 to Day 15 | Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is death, 2 is Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO), 3 is Hospitalized on supplemental oxygen, 4 is Hospitalized not on supplemental oxygen, 5 is Not hospitalized with symptoms and limitation in activity, 6 is Not hospitalized with symptoms but with no limitation in activity, 7 is Not hospitalized without symptoms nor limitation in activity. COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | on or at Day 29 | Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is death, 2 is Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO), 3 is Hospitalized on supplemental oxygen, 4 is Hospitalized not on supplemental oxygen, 5 is Not hospitalized with symptoms and limitation in activity, 6 is Not hospitalized with symptoms but with no limitation in activity, 7 is Not hospitalized without symptoms nor limitation in activity. COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial. |
| Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of patients hospitalized from Day 1 to 29 (Group 2 and Placebo Control Group) |
| Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of days from enrollment to hospitalization (Group 2 and Placebo Control Group) |
| Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of days from enrollment to resolution of COVID-19 symptoms (Group 2 and Placebo Control Group) |
| All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Survival status (All-cause, all-location mortality) from Day 1 to Day 29 (Group 2 and Placebo Control Group) |
| Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | on or at Day 8 | Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is death, 2 is Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO), 3 is Hospitalized on supplemental oxygen, 4 is Hospitalized not on supplemental oxygen, 5 is Not hospitalized with symptoms and limitation in activity, 6 is Not hospitalized with symptoms but with no limitation in activity, 7 is Not hospitalized without symptoms nor limitation in activity. COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial. |
| Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of days without fever from Day 1 to Day 29 (Group 2 and Placebo Control Group) |
| Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of days without ventilator use from Day 1 to Day 29 (Group 2 and Placebo Control Group) |
| ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of days outside the ICU from Day 1 to Day 29 (Group 2 and Placebo Control Group) |
| Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of days outside the hospital from Day 1 to Day 29 (Group 2 and Placebo Control Group) |
| Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of vasopressor-free days through Study Day 29 (Group 2 and Placebo Control Group) |
| Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Day 1 to Day 29 | Number of Days without oxygen Day 1 to Day 29 (Group 2 and Placebo Control Group) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1- Hydroxychloroquine Hydroxychloroquine 400 mg orally twice daily for two doses (Day 1), then 200 mg twice daily for subsequent eight doses (Day 2-5), then placebo twice daily for subsequent eighteen doses (Day 6-14).
Arm Terminated 6/22/2020 | 4 |
| Group 2 - Lopinavir/Ritonavir Lopinavir/Ritonavir 400 mg/100 mg orally twice daily for twenty-eight doses (Days 1-14)
Lopinavir/Ritonavir 400 mg/100 mg: Lopinavir/Ritonavir tablets | 221 |
| Placebo Control Group Placebo Group 1: matched to Hydroxychloroquine orally twice daily for 14 days Placebo Group 2: unmatched orally twice daily for 14 days | 227 |
| Total | 452 |
Baseline characteristics
| Characteristic | Group 1- Hydroxychloroquine | Group 2 - Lopinavir/Ritonavir | Placebo Control Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 215 Participants | 220 Participants | 439 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 20 Participants | 13 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 201 Participants | 213 Participants | 417 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 16 Participants | 16 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 10 Participants | 10 Participants | 21 Participants |
| Race (NIH/OMB) White | 3 Participants | 183 Participants | 191 Participants | 377 Participants |
| Region of Enrollment United States | 4 participants | 221 participants | 227 participants | 452 participants |
| Sex: Female, Male Female | 2 Participants | 129 Participants | 133 Participants | 264 Participants |
| Sex: Female, Male Male | 2 Participants | 92 Participants | 94 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 1 / 221 | 0 / 227 |
| other Total, other adverse events | 2 / 4 | 203 / 221 | 211 / 227 |
| serious Total, serious adverse events | 0 / 4 | 2 / 221 | 1 / 227 |
Outcome results
Primary
Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group)
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is death, 2 is Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO), 3 is Hospitalized on supplemental oxygen, 4 is Hospitalized not on supplemental oxygen, 5 is Not hospitalized with symptoms and limitation in activity, 6 is Not hospitalized with symptoms but with no limitation in activity, 7 is Not hospitalized without symptoms nor limitation in activity. COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
Time frame: Day 1 to Day 15
Population: Includes all randomized participants, Unknown represents those with no daily surveys submitted over the first 15 study days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Death | 0 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Hospitalized on Mechanical Ventilation/ECMO | 1 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Hospitalized on Supplemental Oxygen | 5 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Hospitalized, Not on Supplemental Oxygen | 1 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, Limitations to Daily Activities | 187 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, No Limitations to Daily Activities | 10 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Not Hospitalized, No Symptoms, No Limitations to Daily Activities | 12 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Unknown (no participant response) | 5 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Unknown (no participant response) | 6 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Death | 0 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, Limitations to Daily Activities | 191 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Hospitalized on Mechanical Ventilation/ECMO | 0 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Not Hospitalized, No Symptoms, No Limitations to Daily Activities | 10 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Hospitalized on Supplemental Oxygen | 4 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, No Limitations to Daily Activities | 14 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group) | Hospitalized, Not on Supplemental Oxygen | 2 Participants |
Secondary
All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Survival status (All-cause, all-location mortality) from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2 - Lopinavir/Ritonavir | All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Died | 1 Participants |
| Group 2 - Lopinavir/Ritonavir | All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Alive | 173 Participants |
| Group 2 - Lopinavir/Ritonavir | All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Unknown | 47 Participants |
| Placebo Control Group | All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Died | 0 Participants |
| Placebo Control Group | All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Alive | 195 Participants |
| Placebo Control Group | All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group) | Unknown | 32 Participants |
Secondary
Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of days without fever from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: Related to outcome 6, if symptoms resolved before receiving medication they were not included in this outcome. 13 participants in Group 2 and 6 participants in Placebo Control group did not fill out the data relevant to tracking fever-free days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 16 days |
| Placebo Control Group | Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
Secondary
Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of days outside the hospital from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: Related to outcome 8, if no daily surveys were completed we could not determine ICU-free days. We present the median (IQR), and with almost all participants having no hospitalized days; Median (Q1, Q3) all are 17.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
| Placebo Control Group | Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
Secondary
ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of days outside the ICU from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: Related to outcome 8, if no daily surveys were completed, we could not determine ICU-free days. We present the median (IQR), and with almost all participants having no days in the ICU; Median (Q1, Q3) all are 17.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
| Placebo Control Group | ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
Secondary
Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group)
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is death, 2 is Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO), 3 is Hospitalized on supplemental oxygen, 4 is Hospitalized not on supplemental oxygen, 5 is Not hospitalized with symptoms and limitation in activity, 6 is Not hospitalized with symptoms but with no limitation in activity, 7 is Not hospitalized without symptoms nor limitation in activity. COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
Time frame: on or at Day 29
Population: 58 participants did not complete a survey in Group 2; 38 participants did not complete a survey in the Placebo Control Group.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Hospitalized, Not on Supplemental Oxygen | 1 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, No Limitations to Daily Activities | 11 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Hospitalized on Supplemental Oxygen | 1 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Not Hospitalized, No Symptoms, No Limitations to Daily Activities | 140 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, Limitations to Daily Activities | 9 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Unknown (no participant response) | 58 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Death | 1 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Unknown (no participant response) | 38 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Death | 0 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Hospitalized on Supplemental Oxygen | 0 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Hospitalized, Not on Supplemental Oxygen | 1 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, Limitations to Daily Activities | 11 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, No Limitations to Daily Activities | 16 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group) | Not Hospitalized, No Symptoms, No Limitations to Daily Activities | 161 Participants |
Secondary
Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group)
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is death, 2 is Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO), 3 is Hospitalized on supplemental oxygen, 4 is Hospitalized not on supplemental oxygen, 5 is Not hospitalized with symptoms and limitation in activity, 6 is Not hospitalized with symptoms but with no limitation in activity, 7 is Not hospitalized without symptoms nor limitation in activity. COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
Time frame: on or at Day 8
Population: 41 participants did not complete a survey in Group 2 34 participants did not complete a survey in the Placebo Control Group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Death | 0 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Hospitalized on Mechanical Ventilation/ECMO | 1 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Hospitalized on Supplemental Oxygen | 2 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Hospitalized, Not on Supplemental Oxygen | 0 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, Limitations to Daily Activities | 76 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, No Limitations to Daily Activities | 28 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Not Hospitalized, No Symptoms, No Limitations to Daily Activities | 73 Participants |
| Group 2 - Lopinavir/Ritonavir | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Unknown (No participant response) | 41 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Unknown (No participant response) | 34 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Death | 0 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, Limitations to Daily Activities | 61 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Hospitalized on Mechanical Ventilation/ECMO | 0 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Not Hospitalized, No Symptoms, No Limitations to Daily Activities | 80 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Hospitalized on Supplemental Oxygen | 1 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Not Hospitalized, Symptomatic, No Limitations to Daily Activities | 51 Participants |
| Placebo Control Group | Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group) | Hospitalized, Not on Supplemental Oxygen | 0 Participants |
Secondary
Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group)
Number of patients hospitalized from Day 1 to 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group) | Hospitalized | 7 Participants |
| Group 2 - Lopinavir/Ritonavir | Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group) | Non-hospitalized | 214 Participants |
| Placebo Control Group | Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group) | Hospitalized | 6 Participants |
| Placebo Control Group | Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group) | Non-hospitalized | 221 Participants |
Secondary
Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of Days without oxygen Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: Participants who never filled out a daily survey were excluded since we could not derive oxygen status. We present the median (IQR), and with almost all participants having no days on supplemental oxygen (or with other outcomes); Median (Q1, Q3) all are 17. 5 participants in Group 2 and 6 participants in the placebo never filled out the daily survey.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
| Placebo Control Group | Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
Secondary
Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of days from enrollment to hospitalization (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: Those with a recorded hospitalization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group) | 6 days |
| Placebo Control Group | Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group) | 7 days |
Secondary
Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of days from enrollment to resolution of COVID-19 symptoms (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: If a respondent did not report symptoms on any survey (e.g., if they resolved before receiving the medication), they were not included in the time to symptom resolution based on how we worded it in the SAP (i.e., time from medication receipt to resolution)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 11 days |
| Placebo Control Group | Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 11 days |
Secondary
Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group)
Number of vasopressor-free days through Study Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: We present the median (IQR), with almost all participants having vasopressor-free days throughout primary follow-up; Median (Q1, Q3) all are 17.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group) | 17 days |
| Placebo Control Group | Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group) | 17 days |
Secondary
Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)
Number of days without ventilator use from Day 1 to Day 29 (Group 2 and Placebo Control Group)
Time frame: Day 1 to Day 29
Population: Related to outcome 8, if no daily surveys were completed, we could not derive ventilation status. We present the median (IQR), and with almost all participants having no days on a ventilator; Median (Q1, Q3) all are 17. There was no data for 5 participants in Group 2 and 6 participants in the Placebo Control Group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2 - Lopinavir/Ritonavir | Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |
| Placebo Control Group | Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group) | 17 days |