Trial NCT04960202
Publication EPIC-HR - Hammond J, N Engl J Med (2022) (published paper)
Dates: 2021-07-16 to 2021-12-09
Funding: Private (Pfizer, Inc.)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / Argentina, Brazil, Bulgaria, Czech Republic, Colombia, Hungary, India, Japan, Malaysia, Mexico, Poland, Puerto Rico, Russia, Spain, South Africa, Sout
Follow-up duration (days): 34
Inclusion criteria
  • At least 18 years old
  • confirmed SARS-CoV-2 infection and symptom onset no more than 5 days before randomization, with at least one sign or symptom of Covid-19 on the day of randomization
  • at least one characteristic or coexisting condition associated with high risk of progression to severe Covid-19
Exclusion criteria
  • Previous confirmed SARS-CoV-2 infection or hospitalization for Covid-19
  • anticipated need for hospitalization within 48 hours after randomization
  • prior receipt of convalescent Covid-19 plasma or SARS-CoV-2 vaccine
Interventions
Treatment
Nirmatrelvir/r
300 mg of nirmatrelvir plus 100 mg of ritonavir orally twice daily for 5 days
Control
Placebo

Participants
Randomized
participants :
Nirmatrelvir/r=1120
Placebo=1126
Characteristics of participants
N= 2246
Mean age : NR
1148 males
Severity : Mild: n= 2246/ Asymptomatic: n=0
Number of vaccinated participants: 0
Primary outcome
In the register
Proportion of participants with COVID-19 related hospitalization or death from any cause [Time Frame: Day 1 through Day 28]
In the report
Percentage of patients with Covid-19–related hospitalization or death from any cause through day 28 in the two groups
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to the published article, the registry and the protocol were used in data extraction and assessment of the risk of bias. There is no change from the trial registration in the intervention and control treatments. The primary outcome in the published report reflects that in the registry and protocol, but some secondary outcomes from the registry are not reported in the paper (e.g. the number of COVID-19 related medical visits other than hospitalization and number of days in the hospital and intensive care unit for the treatment of COVID-19 [Time Frame: Day 1 through Day 34]. A planned interim analysis for efficacy and futility with a sample size-re-estimation was conducted and reviewed independently after approximately 45% of overall participants completed the Day 28 assessments in the mITT analysis set (ie, 28 days after randomization). The reason for all discontinuations was summarized by treatment group. Results of the primary outcome were extracted for the patients who were treated ≤5 days from symptom onset and regardless of mAb status in the mITT2 population.