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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 : March 14, 2017
Sponsor:
Information provided by (Responsible Party):
MJM Bonten, UMC Utrecht

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

Condition or disease Intervention/treatment Phase
Community Acquired Pneumonia Drug: Antibiotic A Drug: Antibiotic B Drug: Hydrocortisone Device: Minimal distension Device: Maximal recruitment Device: ECCO2R Phase 4

Detailed Description:
In this study, the investigators aim to build an infrastructure for rapidly obtaining evidence for the management of patients requiring admission to an ICU during a pandemic of severe respiratory infections. Furthermore, during the inter-pandemic phase, this infrastructure will consist of a rolling adaptive clinical trial evaluating different management strategies of patients with severe CAP admitted to ICU. This ongoing trial will serve as the framework in which different aspects of ICU patient management can be rigorously and rapidly evaluated through rapid modification (adaptation) of the trial interventions based on new circumstances (e.g., a pandemic). These modifications or adaptations may include adding "pandemic" study arms (with or without predefined treatment) or changing randomization schemes.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4000 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
Study Start Date : December 2015
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Antibiotic A, no steroid, min dist
Cephalosporin according to local guidelines plus macrolide for at least 7 days + no hydrocortisone for 7 days + invasive mechanical ventilation with "minimal distension" strategy
Drug: Antibiotic A
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Cefotaxim
  • Ceftriaxone
  • Azitromycin
  • Claritromycin
  • Erytromycin

Device: Minimal distension
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with low PEEP settings

Active Comparator: Antibiotic A, no steroid, max recruit
Cephalosporin according to local guidelines plus macrolide for at least 7 days + no hydrocortisone for 7 days + invasive mechanical ventilation with "maximal recruitment strategy"
Drug: Antibiotic A
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Cefotaxim
  • Ceftriaxone
  • Azitromycin
  • Claritromycin
  • Erytromycin

Device: Maximal recruitment
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with high PEEP settings

Active Comparator: Antibiotic A, no steroid, ECCO2R
Cephalosporin according to local guidelines plus macrolide for at least 7 days + no hydrocortisone for 7 days + invasive mechanical ventilation with ECCO2R device
Drug: Antibiotic A
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Cefotaxim
  • Ceftriaxone
  • Azitromycin
  • Claritromycin
  • Erytromycin

Device: ECCO2R
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Names:
  • PALP
  • Novalung
  • Alung

Active Comparator: Antibiotic A, steroid, min dist
Cephalosporin according to local guidelines plus macrolide for at least 7 days + hydrocortisone for 7 days + invasive mechanical ventilation with "minimal distension" strategy
Drug: Antibiotic A
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Cefotaxim
  • Ceftriaxone
  • Azitromycin
  • Claritromycin
  • Erytromycin

Drug: Hydrocortisone
Hydrocortison 100 mg iv every 8 hours for 7 days versus no hydrocortisone

Device: Minimal distension
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with low PEEP settings

Active Comparator: Antibiotic A, steroid, max recruit
Cephalosporin according to local guidelines plus macrolide for at least 7 days + hydrocortisone for 7 days + invasive mechanical ventilation with "maximal recruitment strategy"
Drug: Antibiotic A
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Cefotaxim
  • Ceftriaxone
  • Azitromycin
  • Claritromycin
  • Erytromycin

Drug: Hydrocortisone
Hydrocortison 100 mg iv every 8 hours for 7 days versus no hydrocortisone

Device: Maximal recruitment
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with high PEEP settings

Active Comparator: Antibiotic A, steroid, ECCO2R
Cephalosporin according to local guidelines plus macrolide for at least 7 days + hydrocortisone for 7 days + invasive mechanical ventilation with ECCO2R device
Drug: Antibiotic A
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Cefotaxim
  • Ceftriaxone
  • Azitromycin
  • Claritromycin
  • Erytromycin

Drug: Hydrocortisone
Hydrocortison 100 mg iv every 8 hours for 7 days versus no hydrocortisone

Device: ECCO2R
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Names:
  • PALP
  • Novalung
  • Alung

Active Comparator: Antibiotic B, no steroid, min dist
Respiratory quinolon for at least 7 days + no hydrocortisone for 7 days + invasive mechanical ventilation with "minimal distension" strategy
Drug: Antibiotic B
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Moxifloxacin
  • Levofloxacin

Device: Minimal distension
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with low PEEP settings

Active Comparator: Antibiotic B, no steroid, max recruit
Respiratory quinolon for at least 7 days + no hydrocortisone for 7 days + invasive mechanical ventilation with "maximal recruitment strategy"
Drug: Antibiotic B
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Moxifloxacin
  • Levofloxacin

Device: Maximal recruitment
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with high PEEP settings

Active Comparator: Antibiotic B, no steroid, ECCO2R
Respiratory quinolon for at least 7 days + no hydrocortisone for 7 days + invasive mechanical ventilation with ECCO2R device
Drug: Antibiotic B
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Moxifloxacin
  • Levofloxacin

Device: ECCO2R
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Names:
  • PALP
  • Novalung
  • Alung

Active Comparator: Antibiotic B, steroid, min dist
Respiratory quinolon for at least 7 days + hydrocortisone for 7 days + invasive mechanical ventilation with "minimal distension" strategy
Drug: Antibiotic B
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Moxifloxacin
  • Levofloxacin

Drug: Hydrocortisone
Hydrocortison 100 mg iv every 8 hours for 7 days versus no hydrocortisone

Device: Minimal distension
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with low PEEP settings

Active Comparator: Antibiotic B, steroid, max recruit
Respiratory quinolon for at least 7 days + hydrocortisone for 7 days + invasive mechanical ventilation with "maximal recruitment strategy"
Drug: Antibiotic B
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Moxifloxacin
  • Levofloxacin

Drug: Hydrocortisone
Hydrocortison 100 mg iv every 8 hours for 7 days versus no hydrocortisone

Device: Maximal recruitment
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Name: Mechanical ventilator with high PEEP settings

Active Comparator: Antibiotic B, steroid, ECCO2R
Respiratory quinolon for at least 7 days + hydrocortisone for 7 days + invasive mechanical ventilation with ECCO2R device
Drug: Antibiotic B
Comparison of 3rd generation cephalosporins plus macrolide versus a respiratory quinolone.
Other Names:
  • Moxifloxacin
  • Levofloxacin

Drug: Hydrocortisone
Hydrocortison 100 mg iv every 8 hours for 7 days versus no hydrocortisone

Device: ECCO2R
Comparison of "minimal distension" strategy versus "maximal recruitment" strategy. A third comparison (only in selected sites) is "ultra-protective with maximum of 4 ml/kg ventilation plus ECCO2R.
Other Names:
  • PALP
  • Novalung
  • Alung




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. Ventilator free days. [ Time Frame: Day 30 ]
    Measure the number of ventilator free days of the patients included in this trial at day 30.

  4. Ventilator free days. [ Time Frame: Day 60 ]
    Measure the number of ventilator free days of the patients included in this trial at day 60.

  5. 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.

  6. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

- The trial participants are patients with severe CAP that are admitted to an ICU as part of their routine clinical care.

Overall Platform Inclusion Criteria

In order to be eligible to participate in this study, a patient must meet all five of the following criteria:

  1. Admitted to ICU within 48hrs of hospitalisation
  2. ≥18 years of age
  3. Suspected of community-acquired pneumonia:

    • i) onset of symptoms outside the hospital or long term care facility;
    • ii) Pneumonia is considered the primary admission diagnosis.

    Exclusion Criteria:

    Overall Platform Exclusion Criteria

    A potential eligible patient who meets any of the following criteria will be excluded from participation in this study:

    • Recent institutional exposure within 30 days of presentation to the hospital (to exclude healthcare-associated pneumonia)

    • Resident of nursing home or long term care facility.

    • No commitment to aggressive care; treatment is not aimed at recovery of the patient.

    • Significant trauma, burns

    • On ECMO (Extra Corporal Membrane Oxygenation)

    • Severe chronic liver disease (Child-Pugh class C)

    • Bone marrow transplant or chemotherapy-induced neutropenia.
    • Participation in a competing interventional study (see below 7.5).

    Additional Antibiotic Domain Exclusion criteria

    • Known allergy to one of the study drugs.

    Additional Steroid/Immunomodulatory Domain Exclusion criteria • Patient has received >24 hours of steroid treatment at an immunomodulatory dose (defined as more than 25mg of hydrocortisone, more than 5 mg prednisone or more than 1 mg dexamethasone per 24 hours) prior to randomisation.

    Additional General Ventilatory Domain Inclusion criteria • Intubated within 72 hours of ICU admission;

    • Presence of bilateral alveolar infiltrates on chest X-ray;

    • Moderate to severe ARDS oxygenation criteria (PaO2/FiO2 ratio <200mmHg) on a PEEP of 5cmH2O

    Additional Specific Ventilatory Domain Exclusion Criteria

    • No longer than 48 hours of tracheal intubation and ventilation before randomization;
    • Barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema or the presence of any intercostal catheter),
    • Contraindication for siting of ECCO2R cannulae (ECCO2R arm only)

    Study subjects may be co-enrolled in other research studies when such co-enrolment does not threaten the validity of either study or substantively increase the risk to the study subjects. Approval of co-enrolment with interventional studies will be determined on a case-by-case basis by the study management team.


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: Marc Bonten, Prof. +31 (0) 88 75 573 94 M.J.M.Bonten@umcutrecht.nl
Contact: Lennie Derde, MD +31 (0) 88 755 5555 L.P.G.Derde@umcutrecht.nl

Locations
Belgium
University of Antwerp Not yet recruiting
Edegem, Belgium, 2650
Contact: Herman Goossens, Prof    +32 3 821 37 89    Herman.Goossens@uza.be   
France
Hôpital Cochin Not yet recruiting
Paris, Paris Cedex 14, France, 75679
Contact: Jean-Daniel Chiche, Prof    +33 (0) 158412739 (ICU)    jean-daniel.chiche@cch.aphp.fr   
Germany
Hannover Medical School Not yet recruiting
Hannover, Germany, 30625
Contact: Tobias Welte, Prof         
Ireland
University College Dublin Not yet recruiting
Dublin, Dublin 4, Ireland, D04 V1W8
Contact: Alistair Nichol, Prof.         
Netherlands
UMCU Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Marc Bonten, Prof    +31 88 75 573 94    M.J.M.Bonten@umcutrecht.nl   
Contact: Lennie Derde, MD    +31 (0)88 755 5555    L.P.G.Derde@umcutrecht.nl   
Sponsors and Collaborators
UMC Utrecht
Investigators
Study Chair: Marc Bonten, Prof UMC Utrecht

Additional Information:
Responsible Party: MJM Bonten, Prof. Medical Microbiology, UMC Utrecht
ClinicalTrials.gov Identifier: NCT02735707     History of Changes
Other Study ID Numbers: REMAP-CAP
2015-002340-14 ( EudraCT Number )
602525 ( Other Grant/Funding Number: European Union, FP7-HEALTH-2013-INNOVATION-1 )
First Posted: April 13, 2016    Key Record Dates
Last Update Posted: March 14, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Anti-Bacterial Agents
Moxifloxacin
Levofloxacin
Cephalosporins
Antibiotics, Antitubercular
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
Antineoplastic Agents
Anti-Inflammatory Agents
Anti-Infective Agents, Urinary
Renal Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors