Recruiting NCT02735707

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

Phase III Interventional Community-acquired Pneumonia, Influenza, COVID-19

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Ceftriaxone, Moxifloxacin or Levofloxacin, Piperacillin-tazobactam, Ceftaroline.
Who it may be relevant to: Registry conditions: Community-acquired Pneumonia, Influenza, COVID-19. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Belgium, Canada, Colombia +24
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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.

Detailed 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.

Interventions

Drug Ceftriaxone
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Drug Moxifloxacin or Levofloxacin
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Drug Piperacillin-tazobactam
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Drug Ceftaroline
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice. Note: this intervention is now closed.
Drug Amoxicillin-clavulanate
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Drug Standard course macrolide
Standard course of macrolide therapy, discontinued between study day 3 and the end of study day 5. The dosing of and route of administration is not protocolised, the following guidance is provided: * Initial IV administration of a macrolide is strongly preferred * The preferred IV macrolide is azithromycin, but IV clarithromycin may be substituted. * The preferred enteral macrolide is azithromycin, but enteral clarithromycin or roxithromycin may be substituted.
Drug Extended course macrolide
Extended course of macrolide therapy discontinued at the end of study day 14 or hospital discharge (whichever occurs first). The dosing of and route of administration is not protocolised, the following guidance is provided: * Initial IV administration of a macrolide is strongly preferred * The preferred IV macrolide is azithromycin, but IV clarithromycin may be substituted. * The preferred enteral macrolide is azithromycin, but enteral clarithromycin or roxithromycin may be substituted.
Other No systemic corticosteroid
Patients are not to receive any systemic corticosteroids, including hydrocortisone, to study day 28 or hospital discharge (whichever occurs first).
Drug Fixed-duration Hydrocortisone
50mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days. Note: this intervention is now closed.
Drug Shock-dependent hydrocortisone
50mg IV hydrocortisone every 6 hours while the patient is in septic shock

Primary outcome measures

All-cause mortality [Time frame: Day 90]
Days alive and not receiving organ support in ICU [Time frame: Day 21]

Secondary outcome measures (11)

ICU Mortality [Time frame: Day 90]
ICU length of stay [Time frame: Day 90]
Hospital length of stay [Time frame: Day 90]
Ventilator free days [Time frame: Day 28]
Organ failure free days [Time frame: Day 28]
All-cause mortality [Time frame: 6 months]
Health-related Quality of life assessment [Time frame: 6 months]
Proportion of intubated patients who receive a tracheostomy [Time frame: Day 28]
Destination at time of hospital discharge [Time frame: Free text Day 90]
Readmission to the index ICU during the index hospitalization [Time frame: Day 90]
World Health Organisation 8-point ordinal scale outcome [Time frame: Hospital discharge]

Eligibility criteria

REMAP-CAP PLATFORM INCLUSION CRITERIA:

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

symptoms or signs or both that are consistent with lower respiratory tract infection AND
Radiological evidence of new onset consolidation (in patients with pre-existing radiological changes, evidence of new infiltrate)
Up to 48 hours after ICU admission, receiving organ support with one or more of:

Non-invasive or Invasive ventilatory support;
Receiving infusion of vasopressor or inotropes or both

PLATFORM EXCLUSION CRITERIA:

Healthcare-associated pneumonia:

Prior to this illness, is known to have been an inpatient in any healthcare facility within the last 30 days
Resident of a nursing home or long term care facility
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
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

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
Patient is expected to be discharged from hospital today or tomorrow
More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection.
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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No