REMAP-CAPA Smart, Innovative, Global Platform Trial
REMAP-CAP is a Randomized, Embedded, Multifactorial, Adaptive Platform trial. The broad objective is to, over time, determine and continuously update the optimal set of treatments for community-acquired pneumonia. The purpose of the novel and innovative adaptive trial design is to evaluate a number of treatment options simultaneously and efficiently. This design is able to adapt in the event of pandemics, and increases the likelihood that patients will receive the treatment that is most likely to be effective for them.
A Vast, Solid Network
REMAP-CAP is a global network of leading experts, institutions and research networks, with over 250 participating world-wide, REMAP-CAP is a truly global trial. COMBACTE's CLIN-Net is performing the site selection for REMAP-CAP and aims to select 250 hospitals across Europe.
Unique Trial Design
Community-acquired pneumonia (CAP) is a severe condition in which individuals, who have not been hospitalized recently, develop an acute infection of the lungs. Bacterial and viral infections are responsible for the vast majority of CAP.
All patients who are treated in an ICU will receive therapy that consists of multiple different treatments, as many as 20 or 30.
These treatments act together to treat both the infection and its effects on the body. When treating a patient, doctors choose from many different treatments, most of which are known or believed to be safe and effective. However, doctors don’t always know which treatment option is the better one, as individuals or groups of individuals may respond differently. This study aims to help doctors understand which treatments work best.
REMAP-CAP uses an innovative trial design to efficiently evaluate multiple interventions simultaneously. The video below shows the unique, smart and easy-to-handle design of REMAP-CAP.
“We can test several groups of medicines at the same time. An adaptive platform trial is fairer for the participants. If a particular drug shows better results, a larger percentage of new patients will be allocated to that drug. Fewer people are exposed to less promising medicines. As a result, patients are more likely to benefit from the knowledge that is gradually yielded by the study. We also have faster results.”
Focussed on COVID-19
As an adaptive platform, REMAP-CAP is designed to adapt in the event of a pandemic, increasing the likelihood of patients receiving an effective treatment. Since the COVID-19 outbreak, the platform has extended its domains to investigate new treatments specifically for COVID-19 patients on the ICU and the ward. With the ability to improve the design according to new insights and already having the clinical trial infrastructure in place to implement these insights swiftly, various interventions can be tested simultaneously within multiple therapeutic domains. Shortly after the intensification of the COVID-19 pandemic, five new COVID-19 domains received ethical approval and have been added in the REMAP-CAP trial.
COVID-19 PUBLICATIONS FROM REMAP-CAP
Over the course of a little over a year, a series of REMAP-CAP publications with results from the Pandemic Strata have been published. We look back at the overview below.
REMAP-CAP’s first publication on COVID-19 study results was issued in September 2020 in the Journal of the American Medical Association. It was shown that the use of corticosteroids increases the likelihood of survival of critically ill COVID-19 patients. The results confirm what a study from the University of Oxford previously showed: a third fewer deaths with dexamethasone treatment.
Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19
Results from this study were also included in the WHO meta-analysis published in JAMA on the same day.
COVID-19 Anti-Coagulation Domain
Two papers published in New England Journal of Medicine research from three clinical studies worldwide including REMAP-CAP (and ACTIV-4 and ATTACC), showed that treatment with higher doses of blood thinners Therapeutic anticoagulation improved outcomes in hospitalized COVID-10 patients. Treatment can prevent these patients from becoming seriously ill and can improve the patients’ recovery. However, treatment with such a dose of blood thinners is not effective, and possibly harmful, for patients in the ICU.
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
Therapeutic Anticoagulation with Heparin in Non-Critically Ill Patients with Covid-19
COVID-19 Immunoglobulin Domain
REMAP-CAP examined the effects of administering plasma antibodies to COVID-19 patients. In critically ill COVID-19 patients treated in the ICU, the administration of these antibodies showed no improvement. Shortly after this conclusion, the RECOVERY trial announced no significant difference in 28-day mortality in that trial. Considering these results, the REMAP-CAP ITSC decided to pause recruitment in the Moderate State of this domain.
Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19
COVID-19 Immune Modulation Domain
In February 2021, REMAP-CAP published their paper Interleukin-6 Receptor Antagonists in Critically Ill Patients with COVID-19 in the New England Journal. This paper shows the results of the use of tocilizumab and sarilumab in patients with severe COVID-19.
Adult patients with COVID-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control).
The publication shows that in critically ill patients with COVID-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcome, including survival.
Results from this study were also included in the WHO meta-analysis published in JAMA.
COVID-19 Antiviral Domain
The goal of this domain was to study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with COVID-19. Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
Lopinavir/ritonavir does not improve outcomes for critically ill patients with COVID-19.
REMAP-CAP for YOU
WE4YOU is a 45-minute bi-weekly webinar organized by REMAP-CAP. The webinars cover predefined topics of interest, such as domains or study procedures, with a variety of perspectives. Following each topic presentation by a guest speaker, there is a Q&A session during which attendees can direct questions to a panel of Investigators and Project managers from within REMAP-CAP. Attendees are also invited to suggest topics for this meeting that they would like to see covered. Together, a series of webinars that connects all (prospective) members of the REMAP-CAP family will be built.
You can join WE4YOU every even week on Wednesday at 16.00 CET via ZOOM.
REMAP-CAP Podcast Series
Don’t miss REMAP-CAP’s informative podcast series. With nine episodes and counting, dive into the design, obtained results and publications of this trial together with Critical Care Reviews’ Rob Mac Sweeney and several REMAP-CAP family members.