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

Abstract

Background The 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 The aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. Methods Eligible patients with COVID-19 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 patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the 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 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 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-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 In this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. Trial Registration ClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681 International Registered Report Identifier (IRRID) PRR1-10.2196/23543

Safety and Efficacy of Convalescent Plasma for Severe COVID-19: Interim Report of a Multicenter Phase II Study from Saudi Arabia

“…A summary of the protocol is described here, and the complete protocol has previously been published. [ 6 ]…”

“…In terms of the donors, the trial included adult donors aged ≥18 years who had a prior confirmed COVID-19 diagnosis, as per the current MOH guidelines, and had a complete clinical recovery from COVID-19 before donation (at least 14 days from the last SARS-CoV-2–negative PCR or 28 days from the initial symptoms) and a positive rapid serology test for IgG antibodies against SARS-CoV-2 indicating immunity. [ 3 4 5 6 ] All the MOH guidelines and criteria for routine blood donation and screening regulations were followed; for example, the transfusion of transmissible infection markers in the donor's blood must be negative. In addition, to minimize the risk of transfusion-related acute lung injury (TRALI), CP was only collected from male donors and nulliparous female donors.…”

“…Eligible patients with severe COVID-19 were infused after the consenting process with the donated CP, 300 ml (200–400 ml/treatment dose) at least once, and if required, daily for up to 5 sessions. [ 6 ] For plasma selection, the ABO compatibility was considered, regardless of the Rh status. The CP recipients were monitored for serious adverse effects (SAEs) of FFP transfusion, including anaphylaxis, TRALI and transfusion-associated circulatory overload (TACO).…”

“…For the current study, a group of hematologists, intensivists and infectious disease specialists collaborated to develop a national protocol to investigate the safety, efficacy and feasibility of the administration of CP at a larger scale in different healthcare facilities in the Kingdom of Saudi Arabia (KSA). [ 6 ]…”

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

“…Protocols, programs, and standards have been developed to select donors and collect, process, characterize, store, distribute, and apply CP to patients in need [238,240,242,250], and to conduct clinical trials [239,246,247,254]. Regional and national programs for COVID-19 CP have been established [243,244] as well as a multi-criteria decision-making frame for both CP donor and receipt selection [241].…”