Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)Phase 2EPIC-HOSNCT05545319
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
A Phase 2 study testing Nirmatrelvir and Ritonavir in people with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19), run by Pfizer at 11 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19), Immunocompromised
- What is being tested?
- Nirmatrelvir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 13 Dec 2022to 6 Jan 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
Bulgaria9 sites
Multiprofile Hospital for Active Treatment - Haskovo AD
Haskovo, 6304
Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo EOOD
Haskovo, 6305
Multiprofile Hospital for Active Treatment Sv. Ivan Rilski - Kozloduy EOOD
Kozloduy, Vratsa, 3320
Multiprofile Hospital for Active Treatment - Sveti Nikolay Chudotvoretz
Lom, Montana, 3600
"Specialized Hospital for Active Treatment of Lung Diseases - Pernik" EOOD
Pernik, 2300
"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
Pleven, 5800
MHAT - Heart and Brain
Pleven, 5804
"Multiprofile Hospital for Active Treatment - Medical Complex Sveti Ivan Rilski" EOOD
Plovdiv, 4003
UMHAT "Prof. Dr. Stoyan Kirkovich"AD
Stara Zagora, 6003
United States2 sites
Bassett Medical Center
Cooperstown, New York, 13326
Harlem Hospital Center
New York, New York, 10037
About this study
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
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
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19), Immunocompromised, Hospitalization, Child, Hospitalized
- Being tested
- Nirmatrelvir, Ritonavir, Placebo for nirmatrelvir
- 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
- Medical subject headings
- COVID-19, Respiratory Tract Infections, Infections, Pneumonia, Viral, Pneumonia, Virus Diseases, Coronavirus Infections, Coronaviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NirmatrelvirDrug
Also called Paxlovid
Participants will receive 2 tablets of nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to <60 mL/min) every 12 hours
RitonavirDrug
Also called Norvir
Participants will receive 1 capsule of ritonavir every 12 hours
Placebo for nirmatrelvirDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nirmatrelvir/ritonavir | Experimental | 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 Receives: Drug: Nirmatrelvir; Drug: Ritonavir |
| Placebo/ritonavir | Experimental | Participants will receive placebo 0 mg/ritonavir 100 mg every 12 hours for 15 days. Receives: Drug: Ritonavir; Drug: Placebo for nirmatrelvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal (NP) swabs
Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.
Measured: Day 1 through Day 5
Secondary outcomes (6)
Time to sustained clinical recovery.
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.
Measured: Day 1 through Day 30
Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
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.
Measured: Day 1 through Day 30
Proportion of participants with SARS-CoV-2 RNA <Lower Limit of Quantitation (<LLOQ) (defined as <2.0 log10 copies/mL) in NP swabs
Evaluate effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.
Measured: Day 1 through Day 15
Proportion of participants with sustained NP swab SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL)
To evaluate the effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants.
Measured: Day 15 through Day 45
Incidence of Treatment-Related Adverse Events (TEAEs)
To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants.
Measured: Day 1 through Day 45
Incidence of Adverse Events (AEs) or Serious Adverse Events (SAEs) leading to discontinuations
To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants.
Measured: Day 1 through Day 45
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2022
- Study start13 Dec 2022 (estimated)
- Primary completion21 Sep 2023 (estimated)
- Study completion6 Jan 2024 (estimated)
Why it stopped: 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)Studies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05545319
- Sponsor's protocol ID
- C4671031
- Other IDs
- 2022-002447-22
- Acronym
- EPIC-HOS
- Status last verified
- Feb 2023
- First submitted
- 16 Sep 2022
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05545319
- Acronym / sponsor ID
- EPIC-HOS / C4671031
- Conditions
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19), Immunocompromised, Hospitalization, Child, Hospitalized
- Keywords
- COVID-19, Respiratory Tract Infections, Infections, Pneumonia, Viral, Pneumonia, Virus Diseases, Coronavirus Infections, Coronaviridae Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: 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.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 13 Dec 2022 (estimated)
- Primary completion
- 21 Sep 2023 (estimated)
- Study completion
- 6 Jan 2024 (estimated)
- First posted
- 19 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nirmatrelvir/ritonavir | Experimental | Drug: Nirmatrelvir, Drug: RitonavirParticipants 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 | Experimental | Drug: Ritonavir, Drug: Placebo for nirmatrelvirParticipants will receive placebo 0 mg/ritonavir 100 mg every 12 hours for 15 days. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NirmatrelvirAlso: PaxlovidParticipants will receive 2 tablets of nirmatrelvir (or 1 tablet for participants with eGFR or eCrCl ≥30 to <60 mL/min) every 12 hours | Drug | Nirmatrelvir/ritonavir |
| RitonavirAlso: NorvirParticipants will receive 1 capsule of ritonavir every 12 hours | Drug | Nirmatrelvir/ritonavir, Placebo/ritonavir |
| Placebo for nirmatrelvirParticipants 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. | Drug | Placebo/ritonavir |
Primary outcome
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.
6 secondary outcomes
Time to sustained clinical recovery.
Time frame: Day 1 through Day 30
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
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
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
Incidence of Treatment-Related Adverse Events (TEAEs)
Time frame: Day 1 through Day 45
Incidence of Adverse Events (AEs) or Serious Adverse Events (SAEs) leading to discontinuations
Time frame: Day 1 through Day 45
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nirmatrelvir and Ritonavir in people with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19), run by Pfizer at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Bulgaria, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in SARS-CoV-2 RNA level in nasopharyngeal (NP) swabs (time frame: Day 1 through Day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023.