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

PHASE3RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2016-04-11

Primary completion: 2026-02-01

Study completion finish: 2028-02-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT02735707

Intervention or treatment

DRUG: Ceftriaxone

DRUG: Moxifloxacin or Levofloxacin

DRUG: Piperacillin-tazobactam

DRUG: Ceftaroline

DRUG: Amoxicillin-clavulanate

DRUG: Standard course macrolide

DRUG: Extended course macrolide

OTHER: No systemic corticosteroid

DRUG: Fixed-duration Hydrocortisone

DRUG: Shock-dependent hydrocortisone

DRUG: Fixed-duration higher dose Hydrocortisone

OTHER: No antiviral agent for influenza

DRUG: Five-days oseltamivir

DRUG: Ten-days oseltamivir

OTHER: No antiviral agent for COVID-19

DRUG: Lopinavir / Ritonavir

DRUG: Hydroxychloroquine

DRUG: Hydroxychloroquine + lopinavir/ritonavir

DRUG: Ivermectin

OTHER: No immune modulation for COVID-19

DRUG: Interferon beta-1a

DRUG: Anakinra

DRUG: Tocilizumab

DRUG: Sarilumab

DRUG: Local standard venous thromboprophylaxis

DRUG: Therapeutic dose anticoagulation

DRUG: Conventional low dose thromboprophylaxis

DRUG: Intermediate dose thromboprophylaxis

DRUG: Continuation of therapeutic dose anticoagulation

OTHER: No immunoglobulin

BIOLOGICAL: Convalescent plasma

BIOLOGICAL: Delayed administration of convalescent plasma

OTHER: No vitamin C

DRUG: Vitamin C

OTHER: No antiplatelet

DRUG: Aspirin

DRUG: P2Y12 inhibitor

OTHER: No simvastatin

DRUG: Simvastatin

DRUG: Eritoran

DRUG: Apremilast

PROCEDURE: Clinician-preferred mechanical ventilation strategy

PROCEDURE: Protocolised mechanical ventilation strategy

OTHER: No renin-angiotensin system inhibitor

DRUG: Angiotensin converting enzyme inhibitor

DRUG: Angiotensin Receptor Blockers

DRUG: ARB + DMX-200

OTHER: No cysteamine

DRUG: Cysteamine

DRUG: Fixed-duration dexamethasone

DRUG: Baloxavir Marboxil

DRUG: Five-days oseltamivir + baloxavir marboxil

DRUG: Ten-days oseltamivir + baloxavir marboxil

OTHER: No endothelial modulator

DRUG: Imatinib

OTHER: No Immune Modulator for Influenza

DRUG: Tocilizumab

DRUG: Baricitinib

OTHER: No antiviral agent for COVID-19

DRUG: Nirmatrelvir/ritonavir

DRUG: Remdesivir

DRUG: Nirmatrelvir/ritonavir + remdesivir

Conditions

• Community-acquired Pneumonia, Influenza, COVID-19

Image related to Community-acquired Pneumonia, Influenza, COVID-19

Condition: Community-acquired Pneumonia, Influenza, COVID-19
DRUG: Ceftriaxone and other drugs
Canberra, Australian Capital Territory, Australia and more
Sponsor: UMC Utrecht

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Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Canberra Hospital

Research sites nearby

Select from list below to view details:

Canberra Hospital
Canberra, Australian Capital Territory, Australia
Bankstown-Lidcombe Hospital
Bankstown, New South Wales, Australia
Blacktown Hospital
Blacktown, New South Wales, Australia
Campbelltown Hospital
Campbelltown, New South Wales, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
OTHER: 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. Note: the ceftaroline + macrolide intervention has been closed to recruitment.	DRUG: Ceftriaxone The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
OTHER: 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	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.
OTHER: Corticosteroid Domain Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy. Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19. Note: the fixed-course hydrocortisone has been closed to recruitment	OTHER: No systemic corticosteroid Patients are not to receive any systemic corticosteroids, including hydrocortisone, to study day 28 or hospital discharge (whichever occurs first).
OTHER: Influenza Antiviral Domain Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.	OTHER: No antiviral agent for influenza No antiviral agent intended to be active against influenza infection is to be administered
OTHER: 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: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control. This domain is now closed.	OTHER: No antiviral agent for COVID-19 No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered
OTHER: 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.	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.
OTHER: 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: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain 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.
OTHER: Immunoglobulin Domain Immunosuppressed patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive high-titre convalescent plasma. Note: an earlier version of this domain was not restricted to immunosuppressed patients.	OTHER: No immunoglobulin No immunoglobulin intended to be active against SARS-CoV-2 infection is to be administered.
OTHER: Vitamin C Domain Patients admitted to participating hospitals with community-acquired pneumonia will be randomised to receive no vitamin C, or vitamin C. Note: this domain is now closed.	OTHER: No vitamin C No high dose intravenous vitamin C is to be administered Note: this intervention is now closed.
OTHER: Simvastatin Domain Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no simvastatin, or simvastatin. Note: this domain is now closed.	OTHER: No simvastatin No simvastatin intended to be active against COVID-19 is to be administered Note: this intervention is now closed.
OTHER: 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.	OTHER: No antiplatelet No antiplatelet agent or NSAID to be administered. Note: this intervention is now closed.
OTHER: 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	PROCEDURE: Clinician-preferred mechanical ventilation strategy Clinician-preferred ventilation strategy, including mode of ventilation and all ventilatory parameters
OTHER: 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. Note: this domain is now closed.	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.
OTHER: ACE2 RAS Domain Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies. Note: this domain is now closed.	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. Note: this intervention is now closed.
OTHER: 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. Note: this domain is now closed.	OTHER: No cysteamine No cysteamine to be administered until the end of study day 10 or hospital discharge, whichever occurs first. Note: this intervention is now closed.
OTHER: Endothelial 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 endothelial modulator or enteral imatinib.	OTHER: No endothelial modulator No endothelial modulator (imatinib or another tyrosine kinase inhibitor targeting the same pathway as imatinib) is to be administered.
OTHER: Influenza Immune Modulation Patients with community-acquired pneumonia admitted to participating intensive care units with microbiological testing confirmed influenza infection will be randomised to one of three interventions.	OTHER: No Immune Modulator for Influenza No immune modulating agent intended to be active against influenza is to be administered.
OTHER: COVID-19 Antiviral (II) Domain Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to one of up to four interventions.	OTHER: No antiviral agent for COVID-19 No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
All-cause mortality	Not Specified	Day 90
Days alive and not receiving organ support in ICU	Primary end-point for patients with suspected or proven COVID-19 pandemic infection	Day 21

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
ICU Mortality	Not Specified	Day 90
ICU length of stay	Not Specified	Day 90
Hospital length of stay	Not Specified	Day 90
Ventilator free days	Not Specified	Day 28
Organ failure free days	Not Specified	Day 28
All-cause mortality	Not Specified	6 months
Health-related Quality of life assessment	EQ5D-5L and WHODAS 2.0 (not completed in all regions)	6 months
Proportion of intubated patients who receive a tracheostomy	Not Specified	Day 28
Destination at time of hospital discharge	Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital	Free text Day 90
Readmission to the index ICU during the index hospitalization	Not Specified	Day 90
World Health Organisation 8-point ordinal scale outcome	Not Specified	Hospital discharge

Frequently Asked Questions

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References

Clinical Trials Gov: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia