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

Community-acquired Pneumonia, Influenza, COVID-19 Clinical Trial

— REMAP-CAP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02735707
• Other study ID #: U1111-1189-1653
• Secondary ID: 2015-002340-1460
• Status: Recruiting
• Phase: Phase 3
• Start date: April 11, 2016
• Est. completion date: February 2028

Study information

• Verified date: February 2024
• Source: UMC Utrecht
• Contact: Cameron Green, MSc
• Email: info[@]remapcap.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: February 2028
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Community-acquired Pneumonia, Influenza, COVID-19
• COVID-19
• Pneumonia

Intervention

Drug:
• 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.
• 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.

Other:
• No systemic corticosteroid
Patients are not to receive any systemic corticosteroids, including hydrocortisone, to study day 28 or hospital discharge (whichever occurs first).

Drug:
• 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
• 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.

Other:
• No antiviral agent for influenza
No antiviral agent intended to be active against influenza infection is to be administered

Drug:
• Five-days oseltamivir
Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first)
• Ten-days oseltamivir
Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first)

Other:
• No antiviral agent for COVID-19
No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered

Drug:
• 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.
• 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.
• 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.
• Ivermectin
Ivermectin administered enterally at a dose of 0.2 mg/kg once daily with a maximum daily dose of 24mg/day.

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.

Drug:
• Interferon beta-1a
IFN-ß1a 10 µg will be administered as an intravenous bolus injection via a central or peripheral line. IFN-ß1a will be administered once daily for 6 days or until ICU discharge, whichever occurs first. Note: this intervention is now closed.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Other:
• No immunoglobulin
No immunoglobulin intended to be active against SARS-CoV-2 infection is to be administered. Note: this intervention is now closed.

Biological:
• 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.
• Delayed administration of convalescent plasma
Note: this intervention is now closed.

Other:
• No vitamin C
No high dose intravenous vitamin C is to be administered

Drug:
• Vitamin C
Intravenous Vitamin C 50mg/kg administered every 6 hours for 16 doses

Other:
• No antiplatelet
No antiplatelet agent or NSAID to be administered. Note: this intervention is now closed.

Drug:
• 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.
• P2Y12 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.

Other:
• No simvastatin
No simvastatin intended to be active against COVID-19 is to be administered

Drug:
• Simvastatin
Simvastatin 80mg administered once daily via enteral route, while the patient remains in hospital up to 28 days after randomisation

Other:
• Placebo

Drug:
• 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
• Apremilast
Apremilast administered 30mg twice daily for 14 days or until hospital discharge, whichever occurs first. Note: this intervention is now closed.

Procedure:
• Clinician-preferred mechanical ventilation strategy
Clinician-preferred ventilation strategy, including mode of ventilation and all ventilatory parameters
• Protocolised mechanical ventilation strategy
Invasive mechanical ventilation strategy delivered as outlined in relevant protocol documents for this domain.

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.

Drug:
• 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.
• Angiotensin Receptor Blockers
Site-preferred ARB agent administered as directed by the treating clinician for 10 days or until hospital 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.

Other:
• No cysteamine
No cysteamine to be administered until the end of study day 10 or hospital discharge, whichever occurs first.

Drug:
• 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.
• Fixed-duration dexamethasone
6 mg of IV or enteral dexamethasone will be administered daily for up to 10 days while in hospital.
• Baloxavir Marboxil
Baloxavir marboxil administered on days 1 and 4 post-randomisation.
• 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.
• 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.

Other:
• No endothelial modulator
No endothelial modulator (imatinib or another tyrosine kinase inhibitor targeting the same pathway as imatinib) is to be administered.

Drug:
• 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.

Other:
• No Immune Modulator for Influenza
No immune modulating agent intended to be active against influenza is to be administered.

Drug:
• Tocilizumab
Tocilizumab will be administered as a single dose of 8mg/kg estimated or measured body weight, with a maximum total dose of 800mg. In children weighing less than 30kg, tocilizumab dose will be 12mg/kg. Tocilizumab will be administered as an IV infusion via central or peripheral line over a one-hour period.
• Baricitinib
Baricitinib will be administered at a dose that is determined by age and renal function, for up to 10 days or hospital discharge (whichever occurs first).

Other:
• No antiviral agent for COVID-19
No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered

Drug:
• Nirmatrelvir/ritonavir
Nirmatrelvir-ritonavir will be administered at a dose that is dependent on renal function, for five days.
• Remdesivir
Remdesivir is administered at 200 mg on day one followed by 100 mg daily for a further four doses (i.e., for five doses in total) or until hospital discharge, whichever occurs first.
• Nirmatrelvir/ritonavir + remdesivir
Nirmatrelvir-ritonavir will be administered at a dose that is dependent on renal function, for five days. Remdesivir is administered at 200 mg on day one followed by 100 mg daily for a further four doses (i.e., for five doses in total) or until hospital discharge, whichever occurs first.

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Adelaide	South Australia
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Queen Elizabeth Hospital	Adelaide	South Australia
Australia	Ballarat Base Hospital	Ballarat	Victoria
Australia	Bankstown-Lidcombe Hospital	Bankstown	New South Wales
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Casey Hospital	Berwick	Victoria
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Mater Hospital Brisbane	Brisbane	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	Caboolture Hospital	Caboolture	Queensland
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Sutherland Hospital	Caringbah	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Hospital	Concord	New South Wales
Australia	Queen Elizabeth II Jubilee Hospital	Coopers Plains	Queensland
Australia	Dandenong Hospital	Dandenong	Victoria
Australia	Royal Darwin Hospital,	Darwin	Northern Territory
Australia	Dubbo Base Hospital	Dubbo	New South Wales
Australia	Angliss Hospital	Ferntree Gully	Victoria
Australia	Footscray Hospital	Footscray	Victoria
Australia	Northern Beaches Hospital	Frenchs Forest	New South Wales
Australia	University Hosptial Geelong	Geelong	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St. George Hospital	Kogarah	New South Wales
Australia	Launceston Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Logan Hospital	Logan	Queensland
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	St John of God Hospital Midland	Midland	Western Australia
Australia	St John of God Hospital Murdoch	Murdoch	Western Australia
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Orange Health Service	Orange	New South Wales
Australia	Fiona Stanley Hospital	Perth	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Australia	Redcliffe Hospital	Redcliffe	Queensland
Australia	Maroondah Hospital	Ringwood East	Victoria
Australia	Rockhampton Hospital	Rockhampton	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	St John of God Subiaco	Subiaco	Western Australia
Australia	Sunshine Hospital	Sunshine	Victoria
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	St Vincent's Hospital Sydney	Sydney	New South Wales
Australia	Wollongong Hospital	Sydney	New South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland
Australia	Townsville Hospital	Townsville	Queensland
Australia	Wagga Wagga Base Hospital	Wagga Wagga	New South Wales
Australia	Werribee Mercy Hospital	Werribee	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	AZ Sint-Jan	Brugge
Belgium	CHU de Charleroi - Hôpital Civil Marie Curie	Charleroi
Belgium	Universitair Ziekenhuis Antwerp	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	William Osler Health System	Brampton	Ontario
Canada	Brantford General Hospital	Brantford	Ontario
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	Rockyview General Hospital	Calgary	Alberta
Canada	South Health Campus	Calgary	Alberta
Canada	Royal Alexandra Hospital, Alberta	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Dr. Everett Chalmers Regional Hospital	Fredericton	New Brunswick
Canada	The Moncton Hospital	Fredericton	New Brunswick
Canada	The Saint John General Hospital	Fredericton	New Brunswick
Canada	Hamilton general Hospital	Hamilton	Ontario
Canada	Juravinski Hospital	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Grand River Hospital	Kitchener	Ontario
Canada	St Mary's General Hospital	Kitchener	Ontario
Canada	CIUSS Chaudieres-Appalaches (Levis)	Lévis	Quebec
Canada	Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Hopital du Sacre-Coeur de Montreal	Montréal	Quebec
Canada	Hôpital Fleury	Montréal	Quebec
Canada	Hospital Maisonneuve-Rosemont	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	CHU de Québec - Université Laval	Québec	Quebec
Canada	IUCPQ-UL	Québec	Quebec
Canada	Niagara Health	Saint Catharines	Ontario
Canada	Regina General Hospital	Saskatoon	Saskatchewan
Canada	Centre Hospitalier de l'Université de Sherbrooke	Sherbrooke	Quebec
Canada	Surrey Memorial Hospital	Surrey	British Columbia
Canada	Thunder Bay General Hospital	Thunder Bay	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St Joseph's Health Centre	Toronto	Ontario
Canada	St. Michael's Hospital Unity Health Toronto	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Grace Hospital	Winnipeg	Manitoba
Canada	Health Sciences Centre Winnipeg	Winnipeg	Manitoba
Canada	St Boniface General Hospital	Winnipeg	Manitoba
Colombia	Universidad de La Sabana	Chía	Cundinamarca
Croatia	General County Hospital Požega	Požega
Croatia	University Hospital Centre Zagreb	Zagreb
Croatia	University Hospital for Infectious Diseases	Zagreb
Germany	Charité - Universitätsmedizin Berlin - Infektiologie und Pneumologie	Berlin
Germany	Charité - Universitätsmedizin Berlin - Nephrologie	Berlin
Germany	Vivantes Klinikum Neukölln	Berlin
Germany	Universitätsklinikum Köln	Cologne
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	University Medical Center Hamburg-Eppendorf (UKE)	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitäts Klinikum Tübingen	Tübingen
Germany	Universitätsklinikum Würzburg	Würzburg
Hungary	Jósa András County Hospital	Nyíregyháza
Hungary	Almási Balogh Pál Kórház	Ózd
Hungary	Csolnoky Ferenc Kórház - Veszprem County Hospital	Veszprém
India	Apollo First Med Hospital	Chennai	Tamil Nadu
India	Apollo Main Hospital	Chennai	Tamil Nadu
India	Apollo Speciality Hospital - OMR	Chennai	Tamil Nadu
India	Apollo Vanagaram Hospital	Chennai	Tamil Nadu
Ireland	Beaumont Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	University Hospital Galway	Galway
Japan	St Marianna University School of Medicine	Kawasaki	Kanagawa
Japan	Saiseikai Kumamoto Hospital	Minami	Kumamoto
Japan	Osaka City General Hospital	Osaka
Japan	Itabashi Chuo Medical Center	Tokyo
Japan	Nerima Hikarigaoka Hospital	Tokyo
Japan	Tokyo bay Urayasu-Ichikawa Medical Center	Tokyo
Japan	Tokyo Metropolitan Bokutoh Hospital	Tokyo
Japan	Wakayama Medical University	Wakayama
Japan	St. Marianna University Yokohama City Seibu Hospital	Yokohama	Kanagawa
Japan	Yokohama City University Hospital	Yokohama	Kanagawa
Nepal	Chitwan Medical College	Bharatpur
Nepal	Grande International Hospital	Kathmandu
Nepal	Hospital for Advanced Medicine and Surgery (HAMS)	Kathmandu
Nepal	Nepal Mediciti	Kathmandu
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Martini Hospital Groningen	Groningen
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	University Medical Center Utrecht	Utrecht
New Zealand	CVICU, Auckland City Hospital	Auckland
New Zealand	DCCM, Auckland City Hospital	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	North Shore Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato Hospital	Hamilton
New Zealand	Taranaki Base Hospital	New Plymouth
New Zealand	Rotorua Hospital	Rotorua
New Zealand	Tauranga Hospital	Tauranga
New Zealand	Wellington Regional Hospital	Wellington
New Zealand	Whangarei Hospital	Whangarei
Pakistan	Abbasi Shaheed Hospital	Karachi	Sindh
Pakistan	National Institute of Cardiovascular Diseases, Karachi	Karachi	Sindh
Pakistan	South City Hospital, Karachi	Karachi	Sindh
Pakistan	Ziauddin University Hospital Clifton Campus	Karachi	Sindh
Pakistan	Ziauddin University North Nazimabad Campus	Karachi	Sindh
Portugal	Centro Hospitalar do Medio Tejo	Abrantes
Portugal	Hospital Lusíadas Lisbon	Lisboa
Romania	Clinical Hospital of Infectious and Tropical Diseases "Dr. Victor Babes"	Bucharest
Saudi Arabia	King Abdulaziz Medical City	Riyadh
Spain	Institut Hospital del Mar d'Investigacions Mèdiques	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Neville Hall Hospital	Abergavenny	Wales
United Kingdom	Antrim Area Hospital	Antrim	Northern Ireland
United Kingdom	Basildon Hospital	Basildon	England
United Kingdom	Basingstoke and North Hampshire Hospital	Basingstoke	England
United Kingdom	Royal United Hospital, Bath	Bath	England
United Kingdom	Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	Mater Hospital	Belfast	Northern Ireland
United Kingdom	Royal Victoria Hospital, Belfast	Belfast	Northern Ireland
United Kingdom	Birmingham City Hospital	Birmingham	England
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham	England
United Kingdom	Blackburn Hospital	Blackburn	England
United Kingdom	Glan Clywd Hospital	Bodelwyddan	Wales
United Kingdom	Pilgrim's Hospital	Boston	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Princess of Wales Hospital	Bridgend	Wales
United Kingdom	Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Royal Hospital	Bristol	England
United Kingdom	Southmead Hospital	Bristol	England
United Kingdom	Queen's Hospital, Burton	Burton on Trent	England
United Kingdom	Addenbrookes Hospital	Cambridge	England
United Kingdom	Royal Papworth Hospital	Cambridge	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Cumberland Royal Infirmary	Carlisle	England
United Kingdom	Glangwilli Hospital	Carmarthen	Wales
United Kingdom	Ashford & St Peters Hospital Trust	Chertsey	England
United Kingdom	Countess of Chester Hospital	Chester	England
United Kingdom	Chesterfield Royal Hospital	Chesterfield	England
United Kingdom	Colchester Hospital	Colchester	England
United Kingdom	University Hospital Coventry	Coventry	England
United Kingdom	North Manchester General Hospital	Crumpsall	England
United Kingdom	Grange University Hospital	Cwmbran	Wales
United Kingdom	Darlington Memorial Hospital	Darlington	England
United Kingdom	Darent Valley Hospital	Dartford	England
United Kingdom	Altnagelvin Hospital	Derry	Northern Ireland
United Kingdom	Russells Hall Hospital	Dudley	England
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Frimley Park Hospital	Frimley	England
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	Medway Maritime Hospital	Gillingham	England
United Kingdom	Glasgow Royal Infirmary	Glasgow	Scotland
United Kingdom	Queen Elizabeth University Hospital, Glasgow	Glasgow	Scotland
United Kingdom	James Paget Kings Lynn Hospital	Great Yarmouth	England
United Kingdom	Royal Surrey County Hospital	Guildford	England
United Kingdom	Northwick Park Hospital	Harrow	England
United Kingdom	Hereford County Hospital	Hereford	England
United Kingdom	Barnet Hospital	High Barnet	England
United Kingdom	Huddersfield Hospital	Huddersfield	England
United Kingdom	King George Hospital	Ilford	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Kettering Hospital	Kettering	England
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	England
United Kingdom	Glenfield Hospital	Leicester	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Lincoln County Hospital	Lincoln	England
United Kingdom	Alder Hey Hospital	Liverpool	England
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool	England
United Kingdom	Royal Liverpool Hospital	Liverpool	England
United Kingdom	University Hospital Aintree	Liverpool	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Croydon University Hospital	London	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	King's College Hospital	London	England
United Kingdom	Newham Hospital	London	England
United Kingdom	North Middlesex Hospital	London	England
United Kingdom	Royal Free Hospital	London	England
United Kingdom	Royal London Hospital	London	England
United Kingdom	Royal Marsden Hospital	London	England
United Kingdom	Ryal Brompton	London	England
United Kingdom	St Barts Hosptial	London	England
United Kingdom	St George's Hospital	London	England
United Kingdom	St Mary's Hospital	London	England
United Kingdom	St Thomas' Hospital	London	England
United Kingdom	Whipps Cross Hospital	London	England
United Kingdom	Luton and Dunstable University Hospital	Luton	England
United Kingdom	Maidstone Hospital - Maidstone and Tunbridge Wells NHS Trust	Maidstone	England
United Kingdom	Manchester Royal Infirmary	Manchester	England
United Kingdom	The Christie Hospital	Manchester	England
United Kingdom	Wythenshawe Hospital	Manchester	England
United Kingdom	Queen Elizabeth Hospital, Woolwich	Margate	England
United Kingdom	The James Cook University Hospital	Middlesbrough	England
United Kingdom	Milton Keynes University Hospital	Milton Keynes	England
United Kingdom	Newcastle Freeman Hospital	Newcastle	England
United Kingdom	Royal Victoria Infirmary, Newcastle	Newcastle	England
United Kingdom	Royal Gwent Hospital	Newport	Wales
United Kingdom	Northampton General Hospital	Northampton	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	City Hospital Nottingham	Nottingham	England
United Kingdom	Queen's Medical Centre - Nottingham University Hospitals NHS Trust	Nottingham	England
United Kingdom	George Eliot Hospital	Nuneaton	England
United Kingdom	Royal Oldham Hospital	Oldham	England
United Kingdom	Princess Royal University Hospital	Orpington	England
United Kingdom	John Radcliffe Hospital	Oxford	England
United Kingdom	Royal Alexandra Hospital, Glasgow	Paisley	Scotland
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Royal Glamorgan Hospital	Pontyclun	Wales
United Kingdom	Poole Hospital NHS Foundation Trust	Poole	England
United Kingdom	Queen Alexandra Hospital - Portsmouth Hospitals NHS Trust	Portsmouth	England
United Kingdom	Whiston Hospital	Prescot	England
United Kingdom	Royal Preston Hospital	Preston	England
United Kingdom	Royal Berkshire Hospital	Reading	England
United Kingdom	Alexandra Hospital, Redditch	Redditch	England
United Kingdom	Queen's Hospital Romford	Romford	England
United Kingdom	Rotherham General Hospital	Rotherham	England
United Kingdom	Salford Royal Hospital	Salford	England
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Northern General Hospital	Sheffield	England
United Kingdom	Royal Hallamshire Hospital	Sheffield	England
United Kingdom	Wexham Park Hospital	Slough	England
United Kingdom	South Tyneside District Hospital	South Shields	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Stepping Hill Hospital	Stockport	England
United Kingdom	University Hospital of North Tees	Stockton-on-Tees	England
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent	England
United Kingdom	Sunderland Hospital	Sunderland	England
United Kingdom	King's Mill Hospital	Sutton In Ashfield	England
United Kingdom	Morriston Hospital	Swansea	Wales
United Kingdom	Great Western Hospital	Swindon	England
United Kingdom	Western General Hospital	Swindon	England
United Kingdom	Musgrove Park Hospital	Taunton	England
United Kingdom	Torbay and South Devon Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro	England
United Kingdom	Tunbridge Wells Hospital - Maidstone and Tunbridge Wells NHS Trust	Tunbridge Wells	England
United Kingdom	Harefield Hospital	Uxbridge	England
United Kingdom	Watford General Hospital	Watford	England
United Kingdom	Southend University Hospital	Westcliff-on-Sea	England
United Kingdom	West Cumberland Hospital	Whitehaven	England
United Kingdom	Royal Albert Edward Infirmary	Wigan	England
United Kingdom	Royal Hampshire Hospital	Winchester	England
United Kingdom	Arrow Park Hospital	Wirral	England
United Kingdom	New Cross Hospital	Wolverhampton	England
United Kingdom	Worcester Royal Hospital	Worcester	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales
United Kingdom	York Hospital	York	England
United Kingdom	York Hospital	York	England
United States	University of Michigan	Ann Arbor	Michigan
United States	Augusta University	Augusta	Georgia
United States	University of Illinois Health	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	University of Florida	Jacksonville	Florida
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Centre	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Brown University - Rhode Island Hospital	Providence	Rhode Island
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (11)

Lead Sponsor	Collaborator
UMC Utrecht	Australian and New Zealand Intensive Care Research Centre, Berry Consultants, Global Coalition for Adaptive Research, Intensive Care National Audit & Research Centre, Medical Research Institute of New Zealand, National Intensive Care Surveillance MORU, National University Hospital, Singapore, St. Marianna University School of Medicine, Unity Health, University of Pittsburgh Medical Center

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Colombia,  Croatia,  Germany,  Hungary,  India,  Ireland,  Japan,  Nepal,  Netherlands,  New Zealand,  Pakistan,  Portugal,  Romania,  Saudi Arabia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Occurrence of multi-resistant organism colonisation/infection	Antibiotic Domain specific outcome	Day 90, censored at hospital discharge
Other	Occurrence clostridium difficile	Antibiotic Domain specific outcome	Day 90, censored at hospital discharge
Other	Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death	Macrolide Duration Domain specific outcome.	Day 90, censored at hospital discharge
Other	Change from baseline influenza virus levels in upper and lower respiratory tract specimens	Antiviral Domain specific outcome. Only required at selected sites.	Day 3, up to Day 7
Other	Confirmed deep vein thrombosis	Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.	Between randomisation and hospital discharge
Other	Confirmed pulmonary embolism	Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.	Between randomisation and hospital discharge
Other	Confirmed ischaemic cerebrovascular event	Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.	Between randomisation and hospital discharge
Other	Total red blood cell units transfused	Domain-specific outcome for Anticoagulation and Antiplatelet Domains.	Between randomisation and end of study day 15
Other	Confirmed acute myocardial infarction	Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.	Between randomisation and hospital discharge
Other	Peak troponin	Domain-specific outcome for Anticoagulation and Antiplatelet Domains.	Between randomisation and end of study day 15
Other	Major bleeding event	Domain-specific outcome for Anticoagulation and Antiplatelet Domains.	Between randomisation and end of study day 15
Other	Other confirmed thrombotic event, including mesenteric ischaemia and limb ischaemia	Domain-specific outcome for Anticoagulation, Immunoglobulin, and Antiplatelet Domains.	Between randomisation and hospital discharge
Other	Acute kidney injury (KDIGO stage >= 2 acute kidney injury)	Domain-specific outcome for ACE2 RAS Domain	Between randomisation and 7 days
Other	Change from baseline to peak creatinine	Domain-specific outcome for ACE2 RAS Domain	Between randomisation and 14 days
Other	Angioedema	Domain-specific outcome for ACE2 RAS Domain	Between randomisation and end of study day 12
Other	Change from baseline AST, ALT and bilirubin	Domain-specific outcome for ACE2 RAS Domain	Between randomisation and 14 days
Primary	All-cause mortality		Day 90
Primary	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	ICU Mortality		Day 90
Secondary	ICU length of stay		Day 90
Secondary	Hospital length of stay		Day 90
Secondary	Ventilator free days		Day 28
Secondary	Organ failure free days		Day 28
Secondary	All-cause mortality		6 months
Secondary	Health-related Quality of life assessment	EQ5D-5L and WHODAS 2.0 (not completed in all regions)	6 months
Secondary	Proportion of intubated patients who receive a tracheostomy		Day 28
Secondary	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
Secondary	Readmission to the index ICU during the index hospitalization		Day 90
Secondary	World Health Organisation 8-point ordinal scale outcome		Hospital discharge

External Links

•   PREPARE website
•   REMAP-CAP Study Website