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

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ClinicalTrials.gov Identifier: NCT02735707
Recruitment Status : Recruiting
First Posted : April 13, 2016
Last Update Posted : August 20, 2018
Sponsor:
Collaborators:
Berry Consultants
Australian and New Zealand Intensive Care Research Centre
Medical Research Institute of New Zealand
Information provided by (Responsible Party):
MJM Bonten, UMC Utrecht

Brief Summary:
The purpose of this study is to evaluate the effect of a range of interventions on patients admitted to intensive care with community-acquired pneumonia.

Condition or disease Intervention/treatment Phase
Community-Acquired Pneumonia Drug: Hydrocortisone Drug: Ceftriaxone Drug: Moxifloxacin or Levofloxacin Drug: Piperacillin tazobactam Drug: Ceftaroline Drug: Amoxicillin Clavulanate Drug: Macrolide administered for 3 days Drug: Macrolide administered for up to 14 days Phase 4

Detailed Description:

Patients with pneumonia who are being treated in an ICU will receive many different treatments, as many as 20 or 30, that 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:

  • Test several treatments, at the same time, in the same patient.
  • Look at the results as it goes and uses these results so that new patients in the study have a better chance of getting better treatments
  • Drop treatments if they are shown to be less effective than others
  • Add new treatments to the study as those that have undergone testing complete their evaluation

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6800 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Actual Study Start Date : April 11, 2016
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Active Comparator: Corticosteroid Domain: Hydrocortisone
The patient will receive Hydrocortisone 50 mg every 6 hours for up to 7 days.
Drug: Hydrocortisone
50mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days.

No Intervention: Corticosteroid Domain: No Hydrocortisone
The patient will receive no corticosteroid for 7 days.
Active Comparator: Antibiotic Domain: Ceftriaxone + Macrolide Drug: Ceftriaxone
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Active Comparator: Antibiotic Domain: Moxifloxacin or Levofloxacin Drug: Moxifloxacin or Levofloxacin
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Active Comparator: Antibiotic Domain: Piperacillin-tazobactam + Macrolide Drug: Piperacillin tazobactam
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Active Comparator: Antibiotic Domain: Ceftaroline + Macrolide Drug: Ceftaroline

The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Ceftaroline is not available at commencement.


Active Comparator: Antibiotic Domain: Amoxicillin-clavulanate + Macrolide Drug: Amoxicillin Clavulanate
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Active Comparator: Macrolide Duration Domain: Short course macrolide

The patient will receive macrolide therapy for 3 days, or until legionellosis is excluded.

This arm is nested within the Antibiotic Domain.

Drug: Macrolide administered for 3 days

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.

Active Comparator: Macrolide Duration Domain: Extended course
The patient will receive macrolide therapy for up to 14 days. This arm is nested within the Antibiotic Domain.
Drug: Macrolide administered for up to 14 days

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.




Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: Day 90 ]

Secondary Outcome Measures :
  1. ICU Mortality [ Time Frame: Day 90 ]
  2. ICU length of stay [ Time Frame: Day 90 ]
  3. Hospital length of stay [ Time Frame: Day 90 ]
  4. Ventilator free days [ Time Frame: Day 28 ]
  5. Organ failure free days [ Time Frame: Day 28 ]
  6. All-cause mortality [ Time Frame: 6 months ]
  7. Quality of life assessment [ Time Frame: 6 months ]
    EQ5D-5L and WHODAS 2.0 (not completed in all regions)


Other Outcome Measures:
  1. Occurrence of multi-resistant organism colonisation/infection [ Time Frame: Day 90, censored at hospital discharge ]
    Antibiotic Domain specific outcome

  2. Occurrence clostridium difficile [ Time Frame: Day 90, censored at hospital discharge ]
    Antibiotic Domain specific outcome

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

PLATFORM INCLUSION CRITERIA :

1. Adult patients admitted to an ICU for severe CAP within 48 hours of hospital admission with: i. symptoms or signs or both that are consistent with lower respiratory tract infection AND ii. 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: i. Non-invasive ii. Invasive ventilatory support; iii. Receiving infusion of vasopressor or inotropes

PLATFORM EXCLUSION CRITERIA:

  1. Healthcare-associated pneumonia:

    Prior to this illness, has been i. an inpatient in any healthcare facility within the last 30 days ii. Resident of a nursing home or long term care facility

  2. Death is deemed to be 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

DOMAIN-SPECIFIC ELIGIBLE CRITERIA:

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02735707


Contacts
Contact: Genevieve O' Neill +61 3 9903 0247 info@remapcap.org
Contact: Wilma Van Bentum-Puijk, MD +31 (0) 88 755 5555 prepare_icu@umcutrecht.nl

  Show 36 Study Locations
Sponsors and Collaborators
MJM Bonten
Berry Consultants
Australian and New Zealand Intensive Care Research Centre
Medical Research Institute of New Zealand
Investigators
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 UMC Utrecht, Study Chair REMAP-CAP Europe
Study Chair: Lennie Derde UMC Utrecht, Coordinating Investigator REMAP-CAP Europe

Additional Information:
Responsible Party: MJM Bonten, Prof. Medical Microbiology, UMC Utrecht
ClinicalTrials.gov Identifier: NCT02735707     History of Changes
Other Study ID Numbers: 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: Platform Trial Optimising Interventions in Severe Community Acquired Pneumonia Health Research Council, New Zealand) )
APP1101719 ( Other Grant/Funding Number: OPTIMISE-CAP, The National Health and Medical Research Council, Australia )
First Posted: April 13, 2016    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MJM Bonten, UMC Utrecht:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Anti-Bacterial Agents
Moxifloxacin
Levofloxacin
Cephalosporins
Antibiotics
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Anti-Infective Agents

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Anti-Bacterial Agents
Amoxicillin
Moxifloxacin
Fluoroquinolones
Levofloxacin
Ofloxacin
Ceftriaxone
Tazobactam
Piperacillin
Clavulanic Acid
Clavulanic Acids
Piperacillin, tazobactam drug combination
Penicillanic Acid
Amoxicillin-Potassium Clavulanate Combination
Antibiotics, Antitubercular
Norgestimate, ethinyl estradiol drug combination
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Anti-Infective Agents
Antitubercular Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action