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

Overview

REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia.

The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia.

In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic such as COVID-19.

REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19 in the United States of America.

Description

Community-acquired pneumonia (CAP) that is of sufficient severity to require admission to an intensive care unit (ICU) is associated with substantial mortality.

Patients with pneumonia who are being treated in an ICU will receive therapy that consists of many 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.

This clinical study has been designed in a way that allows the information from patients already in the study to help new patients joining the study. Most studies aren't able to do that. REMAP-CAP has been designed to:

• Evaluate multiple treatment strategies, at the same time, in the same patient.
• Reach platform conclusions when sufficient data is accrued, rather than when a pre-specified sample size is reached
• Utilise data that is already accrued to increase the likelihood that patients within the trial are randomised to treatments that are more likely to be beneficial
• New questions can be substituted into the trial as initial questions are answered, meaning that the trial can be perpetual or open-ended
• Interactions between interventions in different domains can be evaluated

It is reasonable to presume that any pandemic respiratory infection of major significance to public health will manifest as life-threatening respiratory infection including Severe Acute Respiratory illness and severe Community Acquired Pneumonia (CAP) with concomitant admission to hospital, and for some patients, admission to an Intensive Care Unit (ICU). Previous pandemics and more localized outbreaks of respiratory emerging infections have resulted in severe CAP and ICU admission.

Previous pandemics and outbreaks of emerging infectious diseases have outlined the urgent need for evidence, preferably from Randomized Controlled Trials (RCTs), to guide best treatment. However, there are substantial challenges associated with being able to organize such trials when the time of onset of a pandemic and its exact nature are unpredictable. As an adaptive platform trial that enrolls patients during the interpandemic period, REMAP-CAP is ideally positioned to adapt, in the event of a respiratory pandemic, to evaluate existing treatments as well as novel approaches.

Eligibility

REMAP-CAP PLATFORM INCLUSION CRITERIA:

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

   with

   1. symptoms or signs or both that are consistent with lower respiratory tract infection AND
   2. Radiological evidence of new onset consolidation (in patients with pre-existing radiological changes, evidence of new infiltrate)

2. Up to 48 hours after ICU admission, receiving organ support with one or more of:
   1. Non-invasive or Invasive ventilatory support;
   2. Receiving infusion of vasopressor or inotropes or both

PLATFORM EXCLUSION CRITERIA:

1. Healthcare-associated pneumonia:
   1. Prior to this illness, is known to have been an inpatient in any healthcare facility within the last 30 days
   2. Resident of a nursing home or long term care facility
2. Death is deemed to be imminent and inevitable during the next 24 hours 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

REMAP-COVID PLATFORM INCLUSION CRITERIA

1. Adult patients (≥ 18 years) admitted to hospital with acute illness due to suspected or proven pandemic infection.

REMAP-COVID PLATFORM EXCLUSION CRITERIA

1. Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
2. Patient is expected to be discharged from hospital today or tomorrow
3. More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection.
4. Previous participation in this REMAP within the last 90 days

DOMAIN-SPECIFIC ELIGIBLE CRITERIA:

        Each domain may have additional eligibility criteria. Refer to the study website for more
        information (www.remapcap.org).