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Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (REMAP-CAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02735707
Recruitment Status : Recruiting
First Posted : April 13, 2016
Last Update Posted : December 21, 2021
Sponsor:
Collaborators:
Australian and New Zealand Intensive Care Research Centre
Medical Research Institute of New Zealand
Unity Health
Berry Consultants
Global Coalition for Adaptive Research
University of Pittsburgh Medical Center
Intensive Care National Audit & Research Centre
St. Marianna University School of Medicine
National Intensive Care Surveillance MORU
Information provided by (Responsible Party):
Lennie Derde, UMC Utrecht

Tracking Information
First Submitted Date  ICMJE December 11, 2015
First Posted Date  ICMJE April 13, 2016
Last Update Posted Date December 21, 2021
Actual Study Start Date  ICMJE April 11, 2016
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2020)
  • All-cause mortality [ Time Frame: Day 90 ]
  • Days alive and not receiving organ support in ICU [ Time Frame: Day 21 ]
    Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Original Primary Outcome Measures  ICMJE
 (submitted: April 6, 2016)
Mortality (%) measured at day 60 after randomization of the patients included in this trial. [ Time Frame: 60 days ]
Mortality (%) measured at day 60 after randomization of the patients included in this trial for all different interventions.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • 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 ]
    EQ5D-5L and WHODAS 2.0 (not completed in all regions)
  • Proportion of intubated patients who receive a tracheostomy [ Time Frame: Day 28 ]
  • Destination at time of hospital discharge [ Time Frame: Free text Day 90 ]
    Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2016)
  • ICU length of stay of the patients included in this trial. [ Time Frame: Through study completion, average of 6 days ]
    ICU length of stay of the patients included in this trial, measured in number of days for all interventions
  • Hospital length of stay of the patients included in this trial. [ Time Frame: Through study completion, average of 10 days ]
    Hospital length of stay of the patients included in this trial, measured in number of days for all interventions.
  • Ventilator free days. [ Time Frame: Day 30 ]
    Measure the number of ventilator free days of the patients included in this trial at day 30.
  • Ventilator free days. [ Time Frame: Day 60 ]
    Measure the number of ventilator free days of the patients included in this trial at day 60.
  • Organ failure free days. [ Time Frame: Day 30 ]
    Measure the number of organ failure free days of the patients included in this trial at day 30.
  • Organ failure free days. [ Time Frame: Day 60 ]
    Measure the number of organ failure free days of the patients included in this trial at day 60.
Current Other Pre-specified Outcome Measures
 (submitted: December 3, 2021)
  • Occurrence of multi-resistant organism colonisation/infection [ Time Frame: Day 90, censored at hospital discharge ]
    Antibiotic Domain specific outcome
  • Occurrence clostridium difficile [ Time Frame: Day 90, censored at hospital discharge ]
    Antibiotic Domain specific outcome
  • Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death [ Time Frame: Day 90, censored at hospital discharge ]
    Macrolide Duration Domain specific outcome.
  • Change from baseline influenza virus levels in upper and lower respiratory tract specimens [ Time Frame: Day 3, up to Day 7 ]
    Antiviral Domain specific outcome. Only required at selected sites.
  • Confirmed deep vein thrombosis [ Time Frame: Between randomisation and hospital discharge ]
    Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
  • Confirmed pulmonary embolism [ Time Frame: Between randomisation and hospital discharge ]
    Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
  • Confirmed ischaemic cerebrovascular event [ Time Frame: Between randomisation and hospital discharge ]
    Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
  • Total red blood cell units transfused [ Time Frame: Between randomisation and end of study day 15 ]
    Domain-specific outcome for Anticoagulation and Antiplatelet Domains.
  • Confirmed acute myocardial infarction [ Time Frame: Between randomisation and hospital discharge ]
    Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
  • Peak troponin [ Time Frame: Between randomisation and end of study day 15 ]
    Domain-specific outcome for Anticoagulation and Antiplatelet Domains.
  • Major bleeding event [ Time Frame: Between randomisation and end of study day 15 ]
    Domain-specific outcome for Anticoagulation and Antiplatelet Domains.
  • Other confirmed thrombotic event, including mesenteric ischaemia and limb ischaemia [ Time Frame: Between randomisation and hospital discharge ]
    Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
  • Acute kidney injury (KDIGO stage >= 2 acute kidney injury) [ Time Frame: Between randomisation and 7 days ]
    Domain-specific outcome for ACE2 RAS Domain
  • Change from baseline to peak creatinine [ Time Frame: Between randomisation and 14 days ]
    Domain-specific outcome for ACE2 RAS Domain
  • Angioedema [ Time Frame: Between randomisation and end of study day 12 ]
    Domain-specific outcome for ACE2 RAS Domain
  • Change from baseline AST, ALT and bilirubin [ Time Frame: Between randomisation and 14 days ]
    Domain-specific outcome for ACE2 RAS Domain
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Official Title  ICMJE Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:
Adaptive Bayesian Platform Trial evaluating multiple interventions in multiple domains
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Community-acquired Pneumonia, Influenza, COVID-19
Intervention  ICMJE
  • 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.
  • 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.
  • Drug: Shock-dependent hydrocortisone
    50mg IV hydrocortisone every 6 hours while the patient is in septic shock
  • Drug: Fixed-duration higher dose Hydrocortisone

    100mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days.

    Note: this intervention was only available to patients with suspected or proven COVID-19 and is now closed.

  • Other: No antiviral agent for influenza
    No antiviral agent intended to be active against influenza infection is to be administered
  • Drug: Five-days oseltamivir
    Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first)
  • Drug: Ten-days oseltamivir
    Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first)
  • Other: No antiviral agent for COVID-19
    No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered
  • Drug: Lopinavir / Ritonavir

    Lopinavir/ritonavir 400/100mg administered enterally, or 5ml 80/20mg per mL solution suspension via gastric tube, every 12 hours. Administered for a minimum of 5 days, including if discharged from ICU prior to end of study day 5. For patients discharged from ICU between study day 6 and study day 14, lopinavir/ritonavir is ceased at ICU discharge. Lopinavir/ritonavir is ceased at the end of study day 14 if the patient remains in ICU.

    Note: this intervention is now closed.

  • Drug: Hydroxychloroquine

    Loading dose of 800mg hydroxychloroquine administered enterally every 6 hours until 2 doses have been administered. Subsequently, 400mg hydroxychloroquine will be administered enterally every 12 hours for 12 doses or ICU discharge (whichever occurs first).

    Note: this intervention is now closed.

  • Drug: Hydroxychloroquine + lopinavir/ritonavir

    Lopinavir/ritonavir 400/100mg administered enterally, or 5ml 80/20mg per mL solution suspension via gastric tube, every 12 hours. Administered for a minimum of 5 days, including if discharged from ICU prior to end of study day 5. For patients discharged from ICU between study day 6 and study day 14, lopinavir/ritonavir is ceased at ICU discharge. Lopinavir/ritonavir is ceased at the end of study day 14 if the patient remains in ICU.

    Loading dose of 800mg hydroxychloroquine administered enterally every 6 hours until 2 doses have been administered. Subsequently, 400mg hydroxychloroquine will be administered enterally every 12 hours for 12 doses or ICU discharge (whichever occurs first).

    Note: this intervention is now closed.

  • Drug: Ivermectin
    Ivermectin administered enterally at a dose of 0.2 mg/kg once daily with a maximum daily dose of 24mg/day.
  • Other: No immune modulation for COVID-19

    No immune modulating agent intended to be active against COVID-19 is to be administered.

    Note: this intervention is now closed.

  • Drug: Interferon beta-1a

    IFN-β1a 10 μg will be administered as an intravenous bolus injection via a central or peripheral line. IFN-β1a will be administered once daily for 6 days or until ICU discharge, whichever occurs first.

    Note: this intervention is now closed.

    Other Name: IFN-β1a
  • Drug: Anakinra

    A loading dose of 300mg anakinra will be administered as a bolus via central or peripheral line. This is followed by maintenance doses of 100mg of anakinra administered every 6 hours.

    In patients with renal impairment, anakinra will be administered on alternate days.

    Note: this intervention is now closed.

  • Drug: Tocilizumab

    Tocilizumab will be administered as a single dose of 8mg/kg estimated or measured body weight, with a maximum total dose of 800mg.

    Note: this intervention is now closed.

    Tocilizumab will be administered as an IV infusion via central or peripheral line over a one-hour period.

  • Drug: Sarilumab

    Sarilumab will be administered as a single dose of 400mg, via IV infusion through peripheral or central line over a one-hour period.

    Note: this intervention is now closed.

  • Drug: Local standard venous thromboprophylaxis

    Standard venous thromboprophylaxis that complies with local guidelines or usual practice will be administered for 14 days following randomisation or until hospital discharge, whichever occurs first.

    Note: this intervention is now closed.

  • Drug: Therapeutic anticoagulation

    Patients will be administered either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) to achieve systemic anticoagulation. Either agent may be used and the same patient may be switched between UFH and LMWH at the discretion of the treating clinician.

    Note: this intervention is now closed.

  • Drug: Conventional low dose thromboprophylaxis
    Low dose thromboprophylaxis will be administered for 14 days following randomisation or until hospital discharge, whichever occurs first. Dosing is outlined in the relevant protocol documents for this domain.
  • Drug: Intermediate dose thromboprophylaxis
    Intermediate dose thromboprophylaxis will be administered for 14 days following randomisation or until hospital discharge, whichever occurs first. Dosing is outlined in the relevant protocol documents for this domain.
  • Drug: Continuation of therapeutic dose anticoagulation
    Patients already receiving therapeutic dose anticoagulation at the time of randomisation to this intervention will be administered either unfractionated heparin by IV infusion or low-molecular weight heparin to achieve systemic anticoagulation according to local practice for acute VTE treatment for 14 days following randomisation or until hospital discharge, whichever occurs first.
  • Other: No immunoglobulin

    No immunoglobulin intended to be active against SARS-CoV-2 infection is to be administered.

    Note: this intervention is now closed.

  • Biological: Convalescent plasma

    Patients will receive at least one and no more than two units of ABO compatible convalescent plasma within 48 hours of randomisation.

    Note: this intervention is now closed.

  • Biological: Delayed administration of convalescent plasma
    Note: this intervention is now closed.
  • Other: No vitamin C
    No high dose intravenous vitamin C is to be administered
  • Drug: Vitamin C
    Intravenous Vitamin C 50mg/kg administered every 6 hours for 16 doses
  • Other: No antiplatelet

    No antiplatelet agent or NSAID to be administered.

    Note: this intervention is now closed.

  • Drug: Aspirin

    Aspirin administered at either 75mg or 100mg once per day for 14 days or until hospital discharge, whichever occurs first.

    Note: this intervention is now closed.

    Other Name: acetylsalicylic acid
  • Drug: P2Y12 inhibitor

    Site-selected P2Y12 inhibitor:

    • Clopidogrel: administered 75 mg once per day for 14 days or until hospital discharge, whichever occurs first.
    • Prasugrel: If patient is aged less than 75 years and measured or estimated weight if 60kg or more, and initial loading dose of prasugrel 60 mg will be administered, followed by maintenance dose of 10 mg per day.
    • Ticagrelor: administered enterally at 60mg twice daily for 14 days or until hospital discharge, whichever occurs first.

    Note: this intervention is now closed.

    Other Names:
    • Clopidogrel
    • Prasugrel
    • Ticagrelor
  • Other: No simvastatin
    No simvastatin intended to be active against COVID-19 is to be administered
  • Drug: Simvastatin
    Simvastatin 80mg administered once daily via enteral route, while the patient remains in hospital up to 28 days after randomisation
  • Other: Placebo
  • Drug: Eritoran
    Eritoran initiated with a 26.24 mg loading dose (6.56 mg/h IV for 4 hours), followed by a second 13.12 mg loading dose (6.56 mg/h IV for 2 hours) at 12 hours after initiation. Patients will then receive twenty-six 6.56 mg maintenance doses (3.28 mg/h IV for 2 hours) every 12 hours thereafter (total of 14 days). Dosing will be stopped if the patient is discharged from hospital
  • Drug: Apremilast

    Apremilast administered 30mg twice daily for 14 days or until hospital discharge, whichever occurs first.

    Note: this intervention is now closed.

  • Procedure: Clinician-preferred mechanical ventilation strategy
    Clinician-preferred ventilation strategy, including mode of ventilation and all ventilatory parameters
  • Procedure: Protocolised mechanical ventilation strategy
    Invasive mechanical ventilation strategy delivered as outlined in relevant protocol documents for this domain.
  • Other: No renin-angiotensin system inhibitor
    No RAS inhibitor (i.e. no ACEi or ARB) is to be administered up to the end of study day 10.
  • Drug: Angiotensin converting enzyme inhibitor
    Site-preferred ACEi agent administered as directed by the treating clinician for 10 days or until hospital discharge, whichever occurs first.
    Other Names:
    • Ramipril
    • Lisinopril
    • Perindopril
    • Enalapril
    • Trandolapril
    • Captopril
  • Drug: Angiotensin Receptor Blockers
    Site-preferred ARB agent administered as directed by the treating clinician for 10 days or until hospital discharge, whichever occurs first.
    Other Names:
    • Losartan
    • Valsartan
    • Candesartan
    • Irbesartan
    • Telmisartan
    • Olmesartan
  • Drug: ARB + DMX-200

    Site-preferred ARB agent administered in combination with DMX-200 for 10 days or until hospital discharge, whichever occurs first.

    ARB administered as directed by the treating clinician. DMX-200 administered enterally at a dose of 120mg twice daily.

  • Other: No cysteamine
    No cysteamine to be administered until the end of study day 10 or hospital discharge, whichever occurs first.
  • Drug: Cysteamine
    Cysteamine administered every 8 hours at a dose of 5 mg/kg estimated or measured body weight (maximum dose of 500mg), for ten days or until ICU discharge, whichever occurs first.
Study Arms  ICMJE
  • Antibiotic Domain
    Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions
    Interventions:
    • Drug: Ceftriaxone
    • Drug: Moxifloxacin or Levofloxacin
    • Drug: Piperacillin-tazobactam
    • Drug: Ceftaroline
    • Drug: Amoxicillin-clavulanate
  • Macrolide Duration Domain
    Patients with community-acquired pneumonia admitted to participating intensive care units who have been allocated to a beta-lactam antibiotic intervention in the Antibiotic Domain will be randomised to either a standard course or extended course of macrolide therapy
    Interventions:
    • Drug: Standard course macrolide
    • Drug: Extended course macrolide
  • Corticosteroid Domain

    Patients with community acquired pneumonia admitted to participating intensive care units will be randomised to a steroid use strategy

    Note: this domain is now closed to patients with suspected or proven COVID-19

    Interventions:
    • Other: No systemic corticosteroid
    • Drug: Fixed-duration Hydrocortisone
    • Drug: Shock-dependent hydrocortisone
    • Drug: Fixed-duration higher dose Hydrocortisone
  • Influenza Antiviral Domain
    Patients with community-acquired pneumonia admitted to participating intensive care units with suspected or microbiological testing confirmed influenza infection will be randomised to one of three interventions
    Interventions:
    • Other: No antiviral agent for influenza
    • Drug: Five-days oseltamivir
    • Drug: Ten-days oseltamivir
  • COVID-19 Antiviral Domain

    Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin.

    Note: lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine interventions are now closed.

    Interventions:
    • Other: No antiviral agent for COVID-19
    • Drug: Lopinavir / Ritonavir
    • Drug: Hydroxychloroquine
    • Drug: Hydroxychloroquine + lopinavir/ritonavir
    • Drug: Ivermectin
  • COVID-19 Immune Modulation Domain

    Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions.

    Note: this domain is now closed

    Interventions:
    • Other: No immune modulation for COVID-19
    • Drug: Interferon beta-1a
    • Drug: Anakinra
    • Drug: Tocilizumab
    • Drug: Sarilumab
  • Anticoagulation Domain

    Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy.

    Note: the local standard venous thromboprophylaxis and therapeutic anticoagulation interventions are now closed.

    Interventions:
    • Drug: Local standard venous thromboprophylaxis
    • Drug: Therapeutic anticoagulation
    • Drug: Conventional low dose thromboprophylaxis
    • Drug: Intermediate dose thromboprophylaxis
    • Drug: Continuation of therapeutic dose anticoagulation
  • Immunoglobulin Domain

    Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive convalescent plasma.

    Note: this domain is now closed

    Interventions:
    • Other: No immunoglobulin
    • Biological: Convalescent plasma
    • Biological: Delayed administration of convalescent plasma
  • Vitamin C Domain
    Patients admitted to participating hospitals with community-acquired pneumonia will be randomised to receive no vitamin C, or vitamin C
    Interventions:
    • Other: No vitamin C
    • Drug: Vitamin C
  • Simvastatin Domain
    Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no simvastatin, or simvastatin.
    Interventions:
    • Other: No simvastatin
    • Drug: Simvastatin
  • Antiplatelet Domain

    Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no antiplatelet, aspirin, or site-preferred P2Y12 inhibitor.

    Note: this domain is now closed

    Interventions:
    • Other: No antiplatelet
    • Drug: Aspirin
    • Drug: P2Y12 inhibitor
  • Mechanical Ventilation Domain
    Patients with community-acquired pneumonia admitted to participating intensive care units who are intubated and receiving invasive mechanical ventilation will be randomised to protocolised mechanical ventilation strategy, or clinician-preferred mechanical ventilation strategy
    Interventions:
    • Procedure: Clinician-preferred mechanical ventilation strategy
    • Procedure: Protocolised mechanical ventilation strategy
  • COVID-19 Immune Modulation (2) Domain
    Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive one of three interventions
    Interventions:
    • Other: Placebo
    • Drug: Eritoran
    • Drug: Apremilast
  • ACE2 RAS Domain
    Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to three renin-angiotensin system blockade strategies.
    Interventions:
    • Other: No renin-angiotensin system inhibitor
    • Drug: Angiotensin converting enzyme inhibitor
    • Drug: Angiotensin Receptor Blockers
    • Drug: ARB + DMX-200
  • Cysteamine Domain
    Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no cysteamine, or cysteamine
    Interventions:
    • Other: No cysteamine
    • Drug: Cysteamine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 3, 2021)
10000
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2016)
4000
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cameron Green, MSc info@remapcap.org
Contact: Wilma Van Bentum-Puijk, MSc +31 (0) 88 755 5555 EU.remapcap@umcutrecht.nl
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Colombia,   Croatia,   Germany,   Hungary,   India,   Ireland,   Japan,   Nepal,   Netherlands,   New Zealand,   Pakistan,   Portugal,   Romania,   Saudi Arabia,   Spain,   United Kingdom,   United States
Removed Location Countries France
 
Administrative Information
NCT Number  ICMJE NCT02735707
Other Study ID Numbers  ICMJE U1111-1189-1653
2015-002340-14 ( EudraCT Number )
602525 ( Other Grant/Funding Number: European Union, FP7-HEALTH-2013-INNOVATION-1, PREPARE )
16/631 ( Other Grant/Funding Number: Health Research Council of New Zealand )
APP1101719 ( Other Grant/Funding Number: National Health and Medical Research Council, Australia )
158584 ( Other Grant/Funding Number: Canadian Institute of Health Research )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Lennie Derde, UMC Utrecht
Study Sponsor  ICMJE UMC Utrecht
Collaborators  ICMJE
  • Australian and New Zealand Intensive Care Research Centre
  • Medical Research Institute of New Zealand
  • Unity Health
  • Berry Consultants
  • Global Coalition for Adaptive Research
  • University of Pittsburgh Medical Center
  • Intensive Care National Audit & Research Centre
  • St. Marianna University School of Medicine
  • National Intensive Care Surveillance MORU
Investigators  ICMJE
Study Chair: Steve Webb, Prof Monash University, Study Chair REMAP-CAP Australia
Study Chair: Colin McArthur, Dr Medical Research Institute of New Zealand, Study Chair REMAP-CAP New Zealand
Study Chair: Marc Bonten, Prof UMC Utrecht, Study Chair REMAP-CAP Europe
Study Chair: Lennie Derde, MD UMC Utrecht, Coordinating Investigator REMAP-CAP Europe
Study Chair: John Marshall, Prof Unity Health Toronto, Study Chair REMAP-CAP Canada
Study Chair: Derek Angus, Prof University of Pittsburgh Medical Center, Study Chair REMAP-CAP USA
PRS Account UMC Utrecht
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP