COVID-19 MANAGEMENT AND TREATMENT































EPIC-HR trial - Nirmatrelvir + Ritonavir vs Placebo for COVID Infection in Nonhospitalized High-risk Adults, NEJM (2022) [PubMed abstract]
  • The EPIC-HR trial enrolled 2246 adults with laboratory-confirmed COVID and ≥ 1 risk factor for severe COVID
Main inclusion criteria
  • Age ≥ 18 years
  • Laboratory-confirmed COVID infection
  • Symptoms onset within 5 days
  • ≥ 1 risk factor for severe COVID
Main exclusion criteria
  • Previous COVID infection
  • Received COVID vaccine
  • Active liver disease
  • CrCl < 60 ml/min
Baseline characteristics
  • Median age 46 years
  • Symptoms ≤ 3 days - 66%
  • BMI ≥ 25 - 81%
  • Smoker - 39%
Randomized treatment groups
  • Group 1 (1120 patients): Nirmatrelvir 300 mg/Ritonavir 100 mg (Paxlovid) twice daily for 5 days
  • Group 2 (1126 patients): Placebo
Primary outcome: COVID-19 related hospitalization or death from any cause at day 28
Results

Duration: 28 days
Outcome Paxlovid Placebo Comparisons
Primary outcome 0.77% 6.31% p<0.001
COVID hospitalization 0.77% 6.21% N/A
Overall mortality 0 1.15% N/A
Taste perversion 5.6% 0.3% N/A
Diarrhea 3.1% 1.6% N/A
  • Results were similar in the subgroup of patients who were treated within 3 days of symptom onset

Findings: Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns


Paxlovid side effects
Side effect Paxlovid Placebo
Taste perversion 6% <1%
Diarrhea 3% 2%
Hypertension 1% <1%
Myalgia 1% <1%












MOVe-OUT Study - Molnupiravir vs Placebo for COVID Infection in Unvaccinated High-risk Adults, NEJM (2021) [PubMed abstract]
  • The MOVe-OUT study enrolled 1433 unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID and at least one risk factor for severe COVID illness
Main inclusion criteria
  • Nonhospitalized adult
  • Laboratory-confirmed COVID within 5 days
  • Mild or moderate COVID with symptom onset within 5 days
  • ≥ 1 risk factor for severe COVID
  • Unvaccinated
Main exclusion criteria
  • GFR < 30 ml/min
  • Pregnancy
  • Platelet count < 100,000/µL
Baseline characteristics
  • Median age 43 years
  • Obese - 74%
  • Age > 60 years - 17%
  • COVID severity: Mild - 55% | Moderate - 45%
Randomized treatment groups
  • Group 1 (716 patients): Molnupiravir 800 mg twice daily for 5 days
  • Group 2 (717 patients): Placebo
  • Subjects were not allowed to get monoclonal antibody infusions or other COVID treatments
Primary outcome: Incidence of hospitalization for any cause (defined as ≥ 24 hours of acute care in a hospital or any similar facility) or death through day 29
Results

Duration: 29 days
Outcome Molnupiravir Placebo Comparisons
Primary outcome (final analysis) 6.8% 9.7% Diff -3%, 95%CI [-5.9% to -0.1%]
Overall mortality (final analysis) 0.1% (1 person) 1.3% (9 people) N/A
Primary outcome (interim analysis) 7.3% 14.1% p=0.0024
  • The final analysis was provided in the molnupiravir fact sheet. Interim results are from the NEJM article.
  • Side effects were generally mild and similar between groups
  • In an analysis that was not adjusted for multiplicity, the efficacy benefit with molnupiravir treatment was consistent in many subgroups, including participants infected with the delta, gamma, and mu variants of SARS-CoV-2 according to the available baseline clade data

Findings: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19














  • In all 3 trials, randomized patients had ≥ 1 risk factor for severe COVID
  • In the bamlanivimab/etesevimab and casirivimab/imdevimab trials, patients were enrolled within 3 days of positive COVID test. In the sotrovimab trial, patients were enrolled within 5 days of symptom onset.
Effectiveness of antibody treatments in outpatient COVID
Drug Hospitalization or death
by day 29
Comparison PMID
Bamlanivimab + etesevimab
(N=518)
2.1% p<0.001 PMID 34260849
Placebo
(N=517)
7.0%
Casirivimab + imdevimab
(N=736)
1.0% p=0.002 PMID 34587383
Placebo
(N=748)
3.2%
Sotrovimab
(N=528)
1.0% p<0.001 PMID 35285853
Placebo
(N=529)
6.0%