Safety and Efficacy of Convalescent Plasma to Treat Severe COVID-19: Protocol for the Saudi Collaborative Multicenter Phase II Study
Authors: Albalawi Mohammed , Zaidi Syed Ziauddin Ahmed , AlShehry Nawal , AlAskar Ahmed , Zaidi Abdul Rehman Zia , Abdallah Rania Nagib Mohammed , Salam Abdul , AlSagheir Ahmed , AlMozain Nour , Elgohary Ghada , Batarfi Khalid , Alfaraedi Alia , Khojah Osamah , Al-Ansari Rehab , Alfaraj Mona , Dayel Afra , Al Bahrani Ahmed , Abdelhameed Arwa Nabhan , Alhumaidan Hind , Al-Otaibi Jawaher M , Radwi Ghazala , Raizah Abdulrahman , Shatry Hind , Alsaleh Sara , AlZahrani Hazzaa , Al-Hashmi Hani 
Published: September 2020

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