Abstract
BackgroundLate 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform.MethodsWe will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, 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. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, “COVID-19”).DiscussionThis 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.Trial registrationClinicalTrials.govNCT04805125. Registered on March 18, 2021
Highlights
Background and rationale {6a} A new highly contagious coronavirus SARS-CoV-2 has emerged in late 2019 in Wuhan, China, and caused in a 2-month period a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions [1,2,3]
Patients included in the Swiss HIV Cohort Study (SHCS) or the Swiss Transplant Cohort Study (STCS) will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the Corona virus diseases (COVID)-19 mRNA Vaccine Moderna®
Human immunodeficiency virus (HIV)-positive individuals suffer from multiple comorbidities in particular cardiovascular disease and diabetes due to aging, risk factors for chronic diseases, and lifestyle factors, which put them potentially at a higher risk of complicated coronavirus disease-19 (COVID-19) [4]
Summary
Background and rationale {6a} A new highly contagious coronavirus SARS-CoV-2 has emerged in late 2019 in Wuhan, China, and caused in a 2-month period a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions [1,2,3]. Solid organ transplanted patients suffer from multiple chronic conditions like cardiovascular disease and diabetes and are treated with immunosuppressive drugs putting them at risk of multiple infections and severe infection related complications. Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform.
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