Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
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.
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.
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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study 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
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Canberra Hospital
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
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Who is running the clinical trial?
UMC Utrecht
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
| Drug: Ceftriaxone, Drug: Moxifloxacin or Levofloxacin, Drug: Piperacillin-tazobactam, Drug: Ceftaroline, Drug: Amoxicillin-clavulanate |
OTHER: Macrolide Duration Domain
| Drug: Standard course macrolide, Drug: Extended course macrolide |
OTHER: Corticosteroid Domain
| Other: No systemic corticosteroid, Drug: Fixed-duration Hydrocortisone, Drug: Shock-dependent hydrocortisone, Drug: Fixed-duration higher dose Hydrocortisone, Drug: Fixed-duration dexamethasone |
OTHER: Influenza Antiviral Domain
| Other: No antiviral agent for influenza, Drug: Five-days oseltamivir, Drug: Ten-days oseltamivir, Drug: Baloxavir Marboxil, Drug: Five-days oseltamivir + baloxavir marboxil, Drug: Ten-days oseltamivir + baloxavir marboxil |
OTHER: COVID-19 Antiviral Domain
| Other: No antiviral agent for COVID-19, Drug: Lopinavir / Ritonavir, Drug: Hydroxychloroquine, Drug: Hydroxychloroquine + lopinavir/ritonavir, Drug: Ivermectin |
OTHER: COVID-19 Immune Modulation Domain
| Other: No immune modulation for COVID-19, Drug: Interferon beta-1a, Drug: Anakinra, Drug: Tocilizumab, Drug: Sarilumab |
OTHER: Anticoagulation Domain
| 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: Immunoglobulin Domain
| Other: No immunoglobulin, Biological: Convalescent plasma, Biological: Delayed administration of convalescent plasma |
OTHER: Vitamin C Domain
| Other: No vitamin C, Drug: Vitamin C |
OTHER: Simvastatin Domain
| Other: No simvastatin, Drug: Simvastatin |
OTHER: Antiplatelet Domain
| Other: No antiplatelet, Drug: Aspirin, Drug: P2Y12 inhibitor |
OTHER: Mechanical Ventilation Domain
| Procedure: Clinician-preferred mechanical ventilation strategy, Procedure: Protocolised mechanical ventilation strategy |
OTHER: COVID-19 Immune Modulation (2) Domain
| Other: No immune modulation for COVID-19, Drug: Eritoran, Drug: Apremilast |
OTHER: ACE2 RAS Domain
| Other: No renin-angiotensin system inhibitor, Drug: Angiotensin converting enzyme inhibitor, Drug: Angiotensin Receptor Blockers, Drug: ARB + DMX-200 |
OTHER: Cysteamine Domain
| Other: No cysteamine, Drug: Cysteamine |
OTHER: Endothelial Domain
| Other: No endothelial modulator, Drug: Imatinib |
OTHER: Influenza Immune Modulation
| Other: No Immune Modulator for Influenza, Drug: Tocilizumab, Drug: Baricitinib |
OTHER: COVID-19 Antiviral (II) Domain
| Other: No antiviral agent for COVID-19, Drug: Nirmatrelvir/ritonavir, Drug: Remdesivir, Drug: Nirmatrelvir/ritonavir + remdesivir |
What is the study measuring?
Primary Outcome
| Measure | Description | 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
| Measure | Description | 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 |
References
Clinical Trials Gov: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired PneumoniaOther trials to consider
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