Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
Efficacy of Lopinavir-Ritonavir Prophylaxis for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial
22 Pages Posted: 2 Jul 2021More...
Background: Since the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19.
Methods: We conducted a pragmatic open-label, parallel, cluster-randomized superiority trial in four sites in Switzerland and Brazil. Clusters were randomized to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). The primary outcome is the occurrence of COVID-19 within 21 days post-enrollment.
Findings: Of 318 participants, 157 (49.4%) were women, median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomized to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76 to 2.73). In the primary endpoint analysis adjusted for propensity score to receive LPV/r, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.53 (95% CI, 0.23 to 1.23, respectively; P =.14).
Interpretation: LPV/r role as PEP for COVID-19 remains unanswered. In this trial, LPV/r over 5 days did not significantly reduce incidence of COVID-19 in exposed individuals. We observed a change in directionality of the effect in favor of LPV/r after adjusting for baseline SARS-CoV-2 PCR results, indicating a potential role of antivirals in COVID-19 prevention.
Clinical Trial Registration Details: ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732.
Funding Information: Fondation privée des HUG and Swiss National Fund (project number: 33IC30_166819).
Declaration of Interests: None reported.
Ethics Approval Statement: The protocol and amendments were approved by Swissmedic and local ethics committees in Switzerland and Brazil. Participants provided written informed consent before study entry.
Suggested Citation: Suggested Citation