Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19), Immunocompromised, Hospitalization, Child, Hospitalized
Conditions
Keywords
COVID-19, Respiratory Tract Infections, Infections, Pneumonia, Viral, Pneumonia, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, Ribonucleic acid (RNA) virus Infections, Lung Diseases, Respiratory Tract Diseases, Ritonavir, HIV Protease Inhibitors, Viral Protease Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms, Pharmacological Action, Anti-human immunodeficiency virus (HIV) Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, Cytochrome P-450 CYP3A Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Paxlovid, Nirmatrelvir
Brief summary
A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People with Weakened Immune Systems or at Increased Risk for Poor Outcomes who are Hospitalized Due to Severe COVID-19
Interventions
DRUGNirmatrelvir
Participants will receive 2 tablets of nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to \<60 mL/min) every 12 hours
DRUGRitonavir
Participants will receive 1 capsule of ritonavir every 12 hours
Participants will receive 2 tablets of placebo for nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to \<60 mL/min) every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meeting 1 of the 2 categories of COVID-19 risk: * Category A: Immunocompromised * Category B: Non-Immunocompromised, but with ≥2 risk factors * Onset of signs/symptoms attributable to COVID-19 ≤10 days prior to the day of randomization for non-immunocompromised participants (Category B). * Confirmed SARS-CoV-2 infection as determined by Reverse transcription polymerase chain reaction (RT-PCR) or acceptable test method performed by a health care provider in any specimen collected within 48 hours prior to randomization. * Hospitalized for inpatient care for the treatment of clinical manifestations of severe COVID-19. * Requirement for oxygen supplementation (via nasal cannula, mask, non-invasive ventilation \[NIV\] or high flow oxygen) to maintain SpO2 ≥94% at the time of Screening and Randomization.
Exclusion criteria
* Critical illness, defined by ≥1 of the following: * Requirement for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at randomization, or likely to require intermittent mandatory ventilation (IMV) or ECMO within 12 hours of randomization . * Multi-organ dysfunction/failure. * Hemodynamically unstable, eg. septic shock, cardiac failure or requiring vasopressors. * Participant not expected to survive 24 hours from time of randomization. * History of severe chronic liver disease * Receiving dialysis of any kind or severe renal impairment * Use of nirmatrelvir/ritonavir as an outpatient to treat the current COVID-19 related illness ≤7 days of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal (NP) swabs | Day 1 through Day 5 | Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) | Day 1 through Day 30 | Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir treatment on clinical outcomes when added to background usual care, for the treatment of severe COVID-19 in hospitalized participants. |
| Proportion of participants with SARS-CoV-2 RNA <Lower Limit of Quantitation (<LLOQ) (defined as <2.0 log10 copies/mL) in NP swabs | Day 1 through Day 15 | Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants. |
| Time to sustained clinical recovery. | Day 1 through Day 30 | Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir treatment on clinical outcomes when added to background usual care, for the treatment of severe COVID-19 in hospitalized participants. Time to sustained clinical recovery is defined as the first day during the 30 days after randomization in which a participant attains a score of 1, 2, or 3 on the 8-point ordinal scale (ie, remains alive and is either not hospitalized or is hospitalized but no longer requires ongoing inpatient medical care for COVID-19) for at least 7 consecutive days. |
| Incidence of Treatment-Related Adverse Events (TEAEs) | Day 1 through Day 45 | To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants. |
| Incidence of Adverse Events (AEs) or Serious Adverse Events (SAEs) leading to discontinuations | Day 1 through Day 45 | To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants. |
| Proportion of participants with sustained NP swab SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL) | Day 15 through Day 45 | To evaluate the effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants. |
Countries
Bulgaria, United States
Outcome results
None listed