Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (EPIC-HOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05545319
Recruitment Status : Withdrawn (Termination due to challenges related to the operational feasibility of the study, taking into account the current epidemiology and declining hospitalization rates for severe COVID-19.)
First Posted : September 19, 2022
Last Update Posted : March 1, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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

Condition or disease Intervention/treatment Phase
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) Immunocompromised Hospitalization Child, Hospitalized Drug: Nirmatrelvir Drug: Ritonavir Drug: Placebo for nirmatrelvir Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: AN INTERVENTIONAL EFFICACY AND SAFETY, PHASE 2, DOUBLE-BLIND, 2-ARM STUDY TO INVESTIGATE ORALLY ADMINISTERED NIRMATRELVIR/RITONAVIR COMPARED WITH PLACEBO/RITONAVIR FOR THE TREATMENT OF SEVERE COVID-19 IN HOSPITALIZED PARTICIPANTS WHO ARE IMMUNOCOMPROMISED OR AT INCREASED RISK FOR SEVERE COVID-19 OUTCOMES
Estimated Study Start Date : December 13, 2022
Estimated Primary Completion Date : September 21, 2023
Estimated Study Completion Date : January 6, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Nirmatrelvir/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
 Drug: Nirmatrelvir
Participants will receive 2 tablets of nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to <60 mL/min) every 12 hours
Other Name: Paxlovid

Drug: Ritonavir
Participants will receive 1 capsule of ritonavir every 12 hours
Other Name: Norvir
Experimental: Placebo/ritonavir
Participants will receive placebo 0 mg/ritonavir 100 mg every 12 hours for 15 days.
 Drug: Ritonavir
Participants will receive 1 capsule of ritonavir every 12 hours
Other Name: Norvir

Drug: Placebo for nirmatrelvir
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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal (NP) swabs [ Time Frame: 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 :
  1. Time to sustained clinical recovery. [ Time Frame: 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.


  2. Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: 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.

  3. Proportion of participants with SARS-CoV-2 RNA <Lower Limit of Quantitation (<LLOQ) (defined as <2.0 log10 copies/mL) in NP swabs [ Time Frame: 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.

  4. Proportion of participants with sustained NP swab SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL) [ Time Frame: 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.

  5. Incidence of Treatment-Related Adverse Events (TEAEs) [ Time Frame: 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.

  6. Incidence of Adverse Events (AEs) or Serious Adverse Events (SAEs) leading to discontinuations [ Time Frame: 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05545319


Locations
Layout table for location information
United States, New York
Bassett Medical Center
Cooperstown, New York, United States, 13326
Harlem Hospital Center
New York, New York, United States, 10037
Bulgaria
Multiprofile Hospital for Active Treatment - Sveti Nikolay Chudotvoretz
Lom, Montana, Bulgaria, 3600
Multiprofile Hospital for Active Treatment Sv. Ivan Rilski - Kozloduy EOOD
Kozloduy, Vratsa, Bulgaria, 3320
Multiprofile Hospital for Active Treatment - Haskovo AD
Haskovo, Bulgaria, 6304
Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD
Haskovo, Bulgaria, 6305
"Specialized Hospital for Active Treatment of Lung Diseases - Pernik" EOOD
Pernik, Bulgaria, 2300
"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
Pleven, Bulgaria, 5800
MHAT - Heart and Brain
Pleven, Bulgaria, 5804
"Multiprofile Hospital for Active Treatment - Medical Complex Sveti Ivan Rilski" EOOD
Plovdiv, Bulgaria, 4003
UMHAT "Prof. Dr. Stoyan Kirkovich"AD
Stara Zagora, Bulgaria, 6003
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05545319    
Other Study ID Numbers: C4671031
2022-002447-22 ( EudraCT Number )
First Posted: September 19, 2022    Key Record Dates
Last Update Posted: March 1, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Pfizer:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
 Ritonavir
Nirmatrelvir
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors