Continuous Monitoring of Pooled International Trials of Convalescent Plasma for COVID-19 Hospitalized Patients
As the initial COVID-19 pandemic shifted hotspots, an emerging problem for clinical trials became the mismatch between the location of enrolling sites and the current incidence of COVID-19 outbreaks. As a result, many randomized controlled trials (RCTs) were unable to meet their enrollment target. The Continuous Monitoring of Pooled International Trials of Convalescent Plasma for COVID-19 Hospitalized Patients (COMPILE) consortium was our answer to this problem. Read our article describing the principles of this international collaboration in The Journal of the American Medical Association.
The first study initiated by the COMPILE consortium in August 2020 (the COMPILE study) was a real-time pooling of individual patient data from ongoing RCTs to determine as quickly as possible whether COVID-19 convalescent plasma (CCP) is safe and effective as an acute treatment for patients with COVID-19. Ultimately, 8 international RCTs of hospitalized patients from 4 continents became part of the COMPILE consortium and provided individual patient data on 2,341 patients. The main results describing the efficacy of CCP for the acute treatment of COVID-19 were published in JAMA Network Open. An accompanying article in JAMA Network Open investigates the heterogeneity of the CCP effect, and a treatment benefit index was developed that could assist clinicians in recommending this treatment for their patients.
The world continues to learn about the course of COVID-19 and individual patient factors that are related to this course. Two years into the SARS-CoV-2 pandemic, patient characteristics that were not included in the minimal dataset collected for the first study have been identified as potentially important in determining the efficacy of CCP. The COMPILE-Expand study is collecting existing data from patients in the COMPILE study at the time of randomization in the CCP RCTs during patients’ index hospitalization, when patients were hospitalized with COVID-19 and participated in a CCP RCT involved in COMPILE. The goal is to improve on the published treatment benefit index by including the additional baseline patient features.
The COVID-19 pandemic remains a humanitarian crisis because of the uncontrolled spread of SARS-CoV-2, the unpredictable emergence of new variants, and the increasing evidence for new and/or intensified symptoms months after recovery from acute COVID-19. These complications following COVID-19 infection are termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. There is an urgent need for understanding the long-term efficacy of treatments for acute COVID-19 illness. The COMPILE-FollowUp study is assessing COMPILE participants 15 to 33 months after discharge from the index hospitalization, when they were part of an RCT involved in COMPILE. Major clinical events such as vaccination, additional SARS-CoV-2 infections, and symptoms considered to be associated with long COVID will be collected. The goal of the COMPILE-FollowUp study is to assess the long-term efficacy of CCP treatment.
Led by principal investigator Andrea B. Troxel, ScD, from NYU Langone Health, COMPILE has completed the first study and has initiated two additional studies: COMPILE-Expand and COMPILE-FollowUp. The COMPILE consortium offers a secure central repository for the pooled data that is continuously updated with new data. The COMPILE data will be made available to interested researchers after approval of their proposal by the COMPILE Consortium Publications Committee.
Resources for Investigators
If you have questions to discuss with project leadership, email Dr. Troxel at email@example.com.
Collaborating Randomized Controlled Trials
See below for details about RCT protocol titles, locations, and site principal investigators.
A Randomized, Open-Label, Adaptive, Proof-of-Concept Clinical Trial of Donated Antibodies Working Against COVID-19 (DAWN-PLASMA)
University Hospitals Leuven (UZ Leuven), Leuven, Belgium: Geert Meyfroidt, MD, PhD
Convalescent Plasma in the Management of Moderate COVID-19 in India: An Open-Label Parallel-Arm Phase II Multicentre Randomized Controlled Trial (PLACID Trial)
Indian Council of Medical Research (ICMR), New Delhi, India: Aparna Mukherjee, MD, PhD
Brasília Covid-19 Convalescent Plasma (BCCP)
Faculty of Medicine of the University of Brasília, Brazil: André Moraes Nicola, MD
Convalescent Plasma from Recovered Patients to Treat Severe SARS-CoV-2 Disease (CONCOVID Study)
Erasmus University Medical Center, Rotterdam, Netherlands: B.J.A. (Bart) Rijnders, MD, PhD
CONTAIN COVID-19: A Convalescent Plasma to Limit Coronavirus-Associated Complications
NYU Langone Health, New York, NY: Mila B. Ortigoza, MD, PhD
Albert Einstein College of Medicine, New York, NY: Liise-anne Pirofski, MD
Yale University, New Haven, CT: Mahalia Desruisseaux, MD
University of Miami, Miami, FL: Ralph Sacco, MD
University of Texas, Houston, TX: David McPherson, MD
ConPlas-19, a Multicenter, Randomized Clinical Trial of Convalescent Plasma Therapy Versus Standard of Care for the Treatment of COVID-19 in Hospitalized Patients
Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain: Cristina Avendaño-Solá, MD, and Rafael Duarte, MD
A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma to Non-Immune Plasma to Limit Coronavirus-Associated Complications in Hospitalized Patients
University of California, San Francisco, CA: Annie Luetkemeyer, MD, and Priscilla Hsue, MD
An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants with COVID-19 Pneumonia Caused by SARS-CoV-2
University of Pennsylvania, Philadelphia, PA: Katharine Bar, MD