Randomized, Embedded, Multifactorial, Adaptive Platform trial for Community-Acquired Pneumonia

A platform trial for severely ill patients with COVID-19. It aims to generate evidence that can be applied during the pandemic to reduce mortality, reduce ICU use, and reduce morbidity in severely ill patients with COVID-19 infection.

Status: Open, recruiting at ICHT, in set up at Chelwest, Hillingdon, LNWUH and RBHT

IRAS-Number: 237150

CPMS-ID: 38197

Funder: European Commission

Sponsor: University Medical Centre Utrecht (Netherlands)

CI: Prof Anthony Gordon (UK lead)

Approval Date: 27 March 2020

Study Website: https://www.remapcap.org/

Information for Study Teams: https://www.remapcap.org/resources

Description:

REMAP-CAP is an international platform trial that has been specifically designed for a pandemic period. The aim is is to generate evidence that can be applied during the pandemic to reduce mortality, reduce intensive care use, and reduce morbidity in severely ill patients with COVID-19 infection. The platform will test multiple treatments at the same time (antivirals, immune modulation drugs and corticosteroids) and more treatments will be added as new evidence emerges. It is a fully Bayesian adaptive trial. At regular interim analyses, randomisation ratios will weight treatment allocations in favour of the treatment that looks the most promising. If a treatment is beneficial, more patients will be treated with that drug within the trial, improving outcomes and reducing ICU stays, even before the results are declared and the trial ends. It provides a type of self-learning healthcare system, which is important in this fast-moving pandemic.

Inclusion:

1. Adult patient admitted to an ICU for severe CAP within 48 hours of hospital admission with:

  • a) symptoms or signs or both that are consistent with lower respiratory tract infection (for example, acute onset of dyspnea, cough, pleuritic chest pain);

AND

  • b) radiological evidence of new onset consolidation (in-patients with pre-existing radiological changes, evidence of new infiltrate)

2. Requiring organ support with one or more of:

  • a) Non-invasive or invasive ventilatory support;
  • b) Receiving infusion of vasopressor or inotropes or both  


Exclusion:

  1. Healthcare-associated pneumonia: a) Prior to this illness, has been an in-patient in any healthcare facility within the last 30 days b) Resident of a nursing home or long term care facility
  2. Death is deemed imminent or inevitable during this hospital admission AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
  3. Previous participation in this REMAP within the last 90 days
    Patients will be deemed eligible for each treatment domain if they don’t meet any of the following domain specific exclusion criteria

Antibiotic Domain

  1. Received more than 48 hours of intravenous antibiotic treatment for this index illness
  2. More than 24 hours has elapsed since becoming eligible for this domain
  3. Known hypersensitivity to all of the study drugs in the site randomization schedule
  4. A specific antibiotic choice is indicated
  5. The treating clinician believes that participation in the domain would not be in the best interests of the patient

Macrolide Duration Domain (if randomised to a beta-lactam plus macrolide intervention within the Antibiotic Domain)

  1. The treating clinician believes that participation in the domain would not be in the best interests of the patient

Corticosteroid Domain

  1. An indication to prescribe systemic corticosteroids for a reason other than community-acquired pneumonia (CAP) (or severe sepsis) such as chronic corticosteroid use before admission, acute severe asthma, or suspected or proven Pneumocystis jiroveci pneumonia
  2. Have received an immunomodulatory dose of systemic corticosteroid therapy for more than 24 hours prior to the time of enrolment. An immunomodulatory dose is defined as > 20mg of hydrocortisone, > 5mg prednisone, > 4mg methylprednisolone or > 0.8mg dexamethasone per 24 hours.
  3. The treating clinician believes that participation in the domain would not be in the best interests of the patient