Safety and Efficacy of Convalescent Plasma to Treat Severe COVID-19: Protocol for the Saudi Collaborative Multi-center Phase II Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020. OBJECTIVE: To test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. METHODS: Eligible patients with COVID-19 disease will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be those COVID-19 patients who have fully recovered from their disease according to MOH recovery criteria as detailed in inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score (PS) matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients: 115 convalescent plasma recipients and 460 matched controls (1:4 ratio), would be sufficient to detect a clinically important hospital stay & thirty-day mortality difference between the two groups with 80% power and a 5% level of significance. RESULTS: At present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon. CONCLUSIONS: Here, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing feasibility, safety, and potential efficacy of convalescent plasma in treating COVID-19 patients with severe disease. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. CLINICALTRIAL: ClinicalTrials.gov Identifier: NCT04347681 https://clinicaltrials.gov/ct2/show/NCT04347681?term=NCT04347681&draw=2&rank=1.