A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna® Trials
The ongoing SARS-CoV-2 pandemic has highlighted that new, fast and flexible clinical trial approaches are needed to assess the efficacy and safety of interventions in a timely manner. Trial platforms serve as an ideal tool to customize clinical trials while exploiting existing data infrastructures.
Speich et al. performed a pilot trial using a newly developed trial platform nested in the Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). The authors study the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland.
This study is designed as a multicenter, randomized, controlled, open-label, 2-arm clinical trial. Patients included in the SHCS or STCS are eligible for randomization to either the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome is the change in pan-lg antibody response.
In addition, the pilot study will assess endpoints related to trial conduct feasibility, i.e., duration of set-up, time of patient recruitment, patient consent rate, proportion of missing data. Assuming vaccine reactivity of 90% in both vaccine groups, the trial is powered using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025.
In conclusion, this publication describes in-depth the on-going COVERALL study. This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland.