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
- Conditions
- Coronavirus Disease 2019 (COVID-19)HospitalizationChild, HospitalizedSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)Immunocompromised
- Interventions
- Registration Number
- NCT05545319
- Lead Sponsor
- Pfizer
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo/ritonavir Placebo for nirmatrelvir Participants will receive placebo 0 mg/ritonavir 100 mg every 12 hours for 15 days. Nirmatrelvir/ritonavir Nirmatrelvir Participants will receive nirmatrelvir/ ritonavir 300 mg/100 mg (or 150 mg/100 mg for participants with estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCrCl) ≥30 to \<60 mL/min) every 12 hours from Day 1 through Day 15 Nirmatrelvir/ritonavir Ritonavir Participants will receive nirmatrelvir/ ritonavir 300 mg/100 mg (or 150 mg/100 mg for participants with estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCrCl) ≥30 to \<60 mL/min) every 12 hours from Day 1 through Day 15 Placebo/ritonavir Ritonavir Participants will receive placebo 0 mg/ritonavir 100 mg every 12 hours for 15 days.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.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.
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.
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.
Trial Locations
- Locations (11)
Multiprofile Hospital for Active Treatment - Sveti Nikolay Chudotvoretz
🇧🇬Lom, Montana, Bulgaria
Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD
🇧🇬Haskovo, Bulgaria
"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
🇧🇬Pleven, Bulgaria
MHAT - Heart and Brain
🇧🇬Pleven, Bulgaria
"Multiprofile Hospital for Active Treatment - Medical Complex Sveti Ivan Rilski" EOOD
🇧🇬Plovdiv, Bulgaria
UMHAT "Prof. Dr. Stoyan Kirkovich"AD
🇧🇬Stara Zagora, Bulgaria
Multiprofile Hospital for Active Treatment - Haskovo AD
🇧🇬Haskovo, Bulgaria
Harlem Hospital Center
🇺🇸New York, New York, United States
Bassett Medical Center
🇺🇸Cooperstown, New York, United States
Multiprofile Hospital for Active Treatment Sv. Ivan Rilski - Kozloduy EOOD
🇧🇬Kozloduy, Vratsa, Bulgaria
"Specialized Hospital for Active Treatment of Lung Diseases - Pernik" EOOD
🇧🇬Pernik, Bulgaria