The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study....

Area of Science:

• Critical Care Medicine
• Clinical Trial Design
• Infectious Diseases

Background:

• Generating robust evidence for best practice is challenging in heterogeneous intensive care unit (ICU) populations requiring multiple therapies.
• Severe community-acquired pneumonia (CAP) presents a complex clinical scenario necessitating optimized treatment strategies.
• Existing trial methodologies may not adequately address the complexities of multifactorial interventions in critical care.

Purpose of the Study:

• To present the rationale and design of a novel adaptive platform trial for severe community-acquired pneumonia (CAP).
• To determine optimal treatment strategies by comparing multiple interventions across various patient subgroups.
• To establish a flexible platform for continuous evidence generation in critical care settings.

Main Methods:

• A randomized embedded multifactorial adaptive platform trial (REMAP-CAP) design.
• Combines adaptive platform trials with pragmatic point-of-care approaches.
• Randomizes patients to 240 treatment regimens across four domains: antibiotics, antivirals, immunomodulation, and corticosteroids, with response-adaptive randomization.

Main Results:

• The trial generates estimates of superiority, inferiority, and equivalence for various treatment regimens.
• Primary outcome is 90-day mortality, stratified by shock and influenza status.
• The platform is designed for continuous enrollment and rapid adaptation, including for pandemic scenarios like COVID-19.

Conclusions:

• The REMAP-CAP trial design offers a robust method for generating evidence in complex ICU populations.
• This adaptive, multifactorial approach facilitates efficient evaluation of multiple interventions.
• Lessons learned can inform the implementation of similar platform trials in other disease areas.