Have you or your loved ones been diagnosed with community-acquired pneumonia, influenza, covid-19?
You may be eligible to participate in a community-acquired pneumonia, influenza, covid-19 clinical trial.
Have you or your loved ones been diagnosed with community-acquired pneumonia, influenza, covid-19? You may be eligible to participate in a community-acquired pneumonia, influenza, covid-19 clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Community-acquired Pneumonia, Influenza, COVID-19 Clinical Trial
Have you or your loved ones been diagnosed with community-acquired pneumonia, influenza, covid-19?
You may be eligible to participate in a community-acquired pneumonia, influenza, covid-19 clinical trial.
Have you or your loved ones been diagnosed with community-acquired pneumonia, influenza, covid-19? You may be eligible to participate in a community-acquired pneumonia, influenza, covid-19 clinical trial.
Recruiting
Male & Female
18 Years +
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.
Details for the study
Brief Title
Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Official Title
Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Brief Summary
REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for <br /> community-acquired pneumonia. <br /> <br /> The purpose of this study is to evaluate the effect of a range of interventions to improve <br /> outcome of patients admitted to intensive care with community-acquired pneumonia. <br /> <br /> In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple <br /> treatment modalities in the event of a respiratory pandemic such as COVID-19. <br /> <br /> REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19 in <br /> 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.
Treatments and/or Procedures
Delayed administration of convalescent plasma
Note: this intervention is now closed.
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.
Imatinib
Enteral imatinib will be administered as a single 800mg loading dose (study day 1) followed by 400mg daily until study day 14 or discharge.
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.
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.
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.
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.
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.
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.
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.
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.
Therapeutic dose 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.
Vitamin C
Intravenous Vitamin C 50mg/kg administered every 6 hours for 16 doses
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.
Ivermectin
Ivermectin administered enterally at a dose of 0.2 mg/kg once daily with a maximum daily dose of 24mg/day.
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.
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.
Angiotensin receptor blockers
Site-preferred ARB agent administered as directed by the treating clinician for 10 days or until hospital discharge, whichever occurs first.
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.
Apremilast
Apremilast administered 30mg twice daily for 14 days or until hospital discharge, whichever occurs first. Note: this intervention is now closed.
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
Simvastatin
Simvastatin 80mg administered once daily via enteral route, while the patient remains in hospital up to 28 days after randomisation
P 2 y 12 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.
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.
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.
Fixed duration dexamethasone
6 mg of IV or enteral dexamethasone will be administered daily for up to 10 days while in hospital.
Ten days oseltamivir + baloxavir marboxil
Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first), in addition to baloxavir marboxil administered on days 1 and 4 post-randomisation.
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.
Ceftriaxone
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Moxifloxacin or levofloxacin
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Piperacillin tazobactam
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Ceftaroline
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
Amoxicillin clavulanate
The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.
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.
Five days oseltamivir + baloxavir marboxil
Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first), in addition to baloxavir marboxil administered on days 1 and 4 post-randomisation.
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.
Ten days oseltamivir
Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first)
Five days oseltamivir
Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first)
Baloxavir marboxil
Baloxavir marboxil administered on days 1 and 4 post-randomisation.
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.
Fixed duration Hydrocortisone
50mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days.
Shock dependent hydrocortisone
50mg IV hydrocortisone every 6 hours while the patient is in septic shock
Protocolised mechanical ventilation strategy
Invasive mechanical ventilation strategy delivered as outlined in relevant protocol documents for this domain.
Clinician preferred mechanical ventilation strategy
Clinician-preferred ventilation strategy, including mode of ventilation and all ventilatory parameters
No immunoglobulin
No immunoglobulin intended to be active against SARS-CoV-2 infection is to be administered. Note: this intervention is now closed.
No vitamin C
No high dose intravenous vitamin C is to be administered
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.
No cysteamine
No cysteamine to be administered until the end of study day 10 or hospital discharge, whichever occurs first.
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.
No antiplatelet
No antiplatelet agent or NSAID to be administered. Note: this intervention is now closed.
No simvastatin
No simvastatin intended to be active against COVID-19 is to be administered
No endothelial modulator
No endothelial modulator (imatinib or another tyrosine kinase inhibitor targeting the same pathway as imatinib) is to be administered.
No systemic corticosteroid
Patients are not to receive any systemic corticosteroids, including hydrocortisone, to study day 28 or hospital discharge (whichever occurs first).
No antiviral agent for COVID 19
No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered
No antiviral agent for influenza
No antiviral agent intended to be active against influenza infection is to be administered
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Days alive and not receiving organ support in ICU
Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Secondary
Health-related Quality of life assessment
EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Secondary
Destination at time of hospital discharge
Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
Other
Change from baseline AST, ALT and bilirubin
Domain-specific outcome for ACE2 RAS Domain
Other
Angioedema
Domain-specific outcome for ACE2 RAS Domain
Other
Change from baseline to peak creatinine
Domain-specific outcome for ACE2 RAS Domain
Other
Other confirmed thrombotic event, including mesenteric ischaemia and limb ischaemia
Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
Other
Major bleeding event
Domain-specific outcome for Anticoagulation and Antiplatelet Domains.
Other
Peak troponin
Domain-specific outcome for Anticoagulation and Antiplatelet Domains.
Other
Confirmed acute myocardial infarction
Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
Other
Total red blood cell units transfused
Domain-specific outcome for Anticoagulation and Antiplatelet Domains.
Other
Confirmed ischaemic cerebrovascular event
Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
Other
Confirmed deep vein thrombosis
Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
Other
Change from baseline influenza virus levels in upper and lower respiratory tract specimens
Antiviral Domain specific outcome. Only required at selected sites.
Other
Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death
Macrolide Duration Domain specific outcome.
Other
Occurrence clostridium difficile
Antibiotic Domain specific outcome
Other
Occurrence of multi-resistant organism colonisation/infection
Antibiotic Domain specific outcome
Other
Acute kidney injury (KDIGO stage >= 2 acute kidney injury)
Domain-specific outcome for ACE2 RAS Domain
Other
Confirmed pulmonary embolism
Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.
Study Criteria
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).