REMAP-CAP

REMAP-CAP
Name	REMAP-CAP
Type	adaptive platform trial
Start date	2014
Focus	critical care, community-acquired pneumonia, pandemic respiratory infections
Coordinating center	International
Countries	Australia, United Kingdom, United States, Canada, Netherlands, Norway, Spain, Saudi Arabia, others
Principal investigators	Derek Angus; Anthony Gordon; Kathryn Maitland
Status	ongoing

REMAP-CAP REMAP-CAP is an international adaptive platform trial focused on treatments for severe community-acquired pneumonia and pandemic respiratory failure. Launched before the 2019–2023 pandemic, REMAP-CAP rapidly evaluated therapies across multiple treatment domains using Bayesian adaptive methods, enrolling critically ill adults and children in intensive care units. The trial has influenced clinical guidance during public health emergencies and engaged major research networks and regulatory agencies.

Background and objectives

The trial was conceived by investigators affiliated with University of Pittsburgh, Monash University, Imperial College London, University of Oxford, and Johns Hopkins University to address gaps identified after outbreaks including SARS, H1N1 influenza, and MERS-CoV. Primary objectives include identifying effective interventions for severe community-acquired pneumonia, optimizing care in intensive care unit settings, and creating a perpetual platform ready for pandemics akin to COVID-19 pandemic. Secondary aims encompass generating high-quality comparative effectiveness evidence to inform agencies such as the World Health Organization, National Institutes of Health, UK National Health Service, and national research funders.

Trial design and methodology

REMAP-CAP uses a multifactorial, randomized, embedded, adaptive platform design informed by Bayesian statistics developed in collaboration with academic groups including University of Cambridge statisticians and methodologists from London School of Hygiene & Tropical Medicine. The trial integrates response-adaptive randomization, pre-specified adaptive stopping rules, and platform-level master protocols inspired by innovations from RECOVERY (clinical trial), SOLIDARITY trial, and platform trials such as those at Broad Institute. Trial governance incorporated data monitoring committees with expertise from Food and Drug Administration and European Medicines Agency advisors. The design permits simultaneous testing of multiple interventions, addition or removal of domains, and borrowing of information across strata defined by severity and pathogen status.

Interventions and treatment domains

Interventions are organized into treatment domains such as antiviral therapy, immunomodulation, anticoagulation, adjunctive corticosteroids, and respiratory support strategies. Notable domains have evaluated agents and approaches including corticosteroids assessed in relation to protocols used at Royal Brompton Hospital, anticoagulants with guidance from American Society of Hematology, and immunotherapies like interleukin-6 receptor antagonists with considerations parallel to trials at Massachusetts General Hospital and Brigham and Women's Hospital. The platform has tested therapeutic monoclonal antibodies, convalescent plasma in frameworks similar to studies led by Mayo Clinic, and antiviral agents reflective of approaches at Centers for Disease Control and Prevention-partnered studies.

Participants and sites

The trial enrolled critically ill adults and children admitted to intensive care units across a network including academic centers and regional hospitals in countries such as Australia, United Kingdom, United States, Canada, Netherlands, Norway, Spain, and Saudi Arabia. Participant eligibility criteria were harmonized with standards from professional societies like the Society of Critical Care Medicine and pediatric networks including Paediatric Intensive Care Society. Site training, data capture, and implementation strategies leveraged electronic health record collaborations exemplified by Epic Systems partnerships and trial networks such as International Severe Acute Respiratory and Emerging Infection Consortium.

Outcomes and statistical analysis

Primary endpoints emphasized organ support–free days and in-hospital mortality, metrics aligned with outcome frameworks used in trials at Guy's and St Thomas' NHS Foundation Trust and St Thomas' Hospital. Secondary outcomes included duration of mechanical ventilation, length of stay, and long-term functional status measured with instruments similar to those used by National Institute for Health and Care Excellence and rehabilitation cohorts from University College London Hospitals. Statistical analysis employed Bayesian hierarchical models enabling borrowing across subgroups, prespecified thresholds for superiority, futility, and equivalence, and adaptive randomization influenced by interim results—methods with parallels at Duke University and Stanford University biostatistics groups.

Key findings and impact

REMAP-CAP produced influential results during the COVID-19 pandemic, notably demonstrating effects of immunomodulators and anticoagulation strategies that informed guidance from World Health Organization and national regulators. Findings contributed to changing practice at hospital systems including NHS England and Veterans Health Administration, and influenced subsequent trials such as RECOVERY (clinical trial) in designing adaptive elements. The platform's rapid evaluation capacity highlighted model pathways for pandemic research logistics used by organizations like Coalition for Epidemic Preparedness Innovations and funding bodies including Wellcome Trust and National Institute for Health Research.

Governance, ethics, and funding

REMAP-CAP governance comprises international steering committees, domain-specific working groups, and independent data safety monitoring boards with members from institutions such as Harvard Medical School, University of Toronto, and Karolinska Institutet. Ethical oversight was provided through institutional review boards and research ethics committees including those at Oxford University Hospitals and Monash Health, with emergency context provisions for consent paralleling guidance from Council for International Organizations of Medical Sciences. Funding and support have come from a mixture of governmental, charitable, and institutional sources including National Health and Medical Research Council (Australia), UK Research and Innovation, Bill & Melinda Gates Foundation, and in-kind contributions from participating universities and health systems.

Category:Clinical trials