AntiThrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia
- Registration Number
- NCT05848713
- Lead Sponsor
- University of Manitoba
- Brief Summary
This is an international, open-label, stratified randomized controlled trial with Bayesian adaptive stopping rules to compare the effects of therapeutic-dose heparin vs. usual care pharmacological thromboprophylaxis on outcomes in patients admitted to hospital with community acquired pneumonia (CAP).
- Detailed Description
The global incidence of hospitalization due to CAP is high and associated with substantive morbidity and mortality. Thrombotic complications - including venous, arterial, and possibly microvascular - occur commonly in hospitalized patients across many etiologies of CAP. Poor outcomes may be mediated by both inflammatory and thrombotic processes leading to respiratory, cardiac, and other end organ dysfunction. There are currently no established therapies that modify the potentially maladaptive immunothrombosis pathway in CAP.
Therapeutic-dose anticoagulation with heparin reduces disease progression and mortality in non-critically ill patients hospitalized with COVID-19 with an acceptable safety profile. COVID-19 shares pathogenic features, including activation of the inflammatory and coagulation cascades, with other pneumonias. Whether therapeutic-dose heparin confers similar clinical benefits in non-COVID-19 CAP is unknown.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 4000
-
Patients ≥18 years of age
-
Admitted to hospital for a suspected or confirmed diagnosis of CAP defined by:
- Radiographic evidence of new or worsening infiltrate
- One or more of the following signs and/or symptoms of lower respiratory tract infection
i. New or increased cough or sputum production ii. Fever of > 37.8C or temperature < 36C iii. WBC > 11 x 109/L or < 4 x 109/L c. The primary diagnosis is believed to be CAP as per the attending physician
-
Requires supplemental oxygen to treat hypoxemia (or requires an increased level of supplemental oxygen if on chronic oxygen therapy)
-
Hospital admission anticipated to last ≥72 hours from randomization
-
Suspected or confirmed active COVID-19 infection
-
Hospital admission for >72 hours prior to randomization
-
Patients receiving non-invasive or invasive ventilation, vasopressors, or extracorporeal life support (ECLS) within an ICU at the time of enrollment
-
Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization
-
Patients for whom the intent is to not use pharmacologic thromboprophylaxis
-
Patients with an independent indication for therapeutic-dose anticoagulation
-
Patients with a contraindication to therapeutic-dose anticoagulation, including:
- Non-traumatic bleeding that requires medical evaluation or hospitalization within 30 days prior to CAP hospital admission
- History of an inherited or acquired bleeding disorder
- Cerebral aneurysm or mass lesions of the central nervous system
- Ischemic stroke within 3 months of hospital admission
- Gastrointestinal bleeding within 3 months of hospital admission
- Platelet count <50 x109/L OR INR >2.0 OR hemoglobin <80 g/L at the time of screening
- Other physician-perceived contraindications to therapeutic anticoagulation
-
History of heparin induced thrombocytopenia (HIT) or other heparin allergy
-
Current or recent (within 7 days of screening) use of dual anti-platelet inhibitors (For example; Aspirin + one of the following; clopidogrel, ticagrelor, prasugrel)
-
Patients in whom imminent death is anticipated
-
Anticipated transfer to another hospital that is not a study site within 72 hours of randomization
-
Enrollment in other interventional trials related to anticoagulation or antiplatelet therapy during current hospitalization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Therapeutic-Dose Heparin Heparin Participants randomized to the investigational arm will receive a pragmatic strategy of therapeutic-dose low molecular-weight heparin (LMWH) or unfractionated heparin (UFH) administered daily for up to 14 days or until hospital discharge, whichever occurs first. Participants should start receiving study drug as soon as possible following randomization.
- Primary Outcome Measures
Name Time Method Ordinal endpoint reflecting survival 30 days Survival to hospital discharge without ICU-level organ support. Organ support is defined as receipt of high flow nasal oxygen, invasive or non-invasive mechanical ventilation, vasopressor/inotropic therapy, or extracorporeal life support (ECLS) within an ICU. This outcome reflects disease progression to ICU-level organ failure or the worst possible outcome (death). It was chosen because of its importance to patients, clinicians, and other stakeholders. Given the limited number of ICU beds, reducing the burden of critical illness has important health system capacity implications.
- Secondary Outcome Measures
Name Time Method Hospital-free days 30 days, 90 days, and 180 days Days alive outside hospital
Health related quality of life 30 days, 90 days, and 180 days Using the Clinical Frailty Scale instrument
Bleeding events 14 days Number of participants with major bleeds as defined by the ISTH definition.
HIT events 14 days Number of participants with laboratory confirmed heparin induced thrombocytopenia (HIT)
Thrombotic events 30 days and 90 days Number of participants with deep vein thrombosis, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke
Invasive mechanical ventilation 30 days Ordered categorical endpoint with three possible outcomes based on the worst status of each patient through day 30 following randomization
All cause mortality 30 days, 90 days, and 180 days
Trial Locations
- Locations (66)
University of Chicago
🇺🇸Chicago, Illinois, United States
Ochsner Clinic
🇺🇸Jefferson, Louisiana, United States
Maine Medical Centre
🇺🇸Portland, Maine, United States
Henry Ford University
🇺🇸Dearborn, Michigan, United States
Cooper University Health Care
🇺🇸Camden, New Jersey, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Santa Casa de Misericordia de Itabuna
🇧🇷Itabuna, BA, Brazil
Hospital Brasilia
🇧🇷Brasília, DF, Brazil
Hospital Sao Brasilia
🇧🇷Brasília, DF, Brazil
Instituto de Cardiologia e Transplantes do Distrito Federal
🇧🇷Brasília, DF, Brazil
Hospital Estadual Dr. Jayme Santos Neves
🇧🇷Serra, ES, Brazil
Hospital Evangelico de Vila Velha
🇧🇷Vila Velha, ES, Brazil
Hospital Universitário Cassiano Antonio Moraes
🇧🇷Vitória, ES, Brazil
Instituto Goiano de Oncologia e Hematologia - INGOH
🇧🇷Goiania, GO, Brazil
Hospital de Messejana Dr. Carlos Alberto Studart Gomes
🇧🇷Goiânia, GO, Brazil
Hospital Ruy Azeredo
🇧🇷Goiânia, GO, Brazil
Hospital Felicio Rocho
🇧🇷Belo Horizonte, MG, Brazil
NUPEC-Orizonti
🇧🇷Belo Horizonte, MG, Brazil
Hospital do Coração - MS
🇧🇷Campo Grande, MS, Brazil
Hospital Agamenon Magalhães
🇧🇷Recife, PE, Brazil
Hospital Santa Cruz
🇧🇷Curitiba, PR, Brazil
PUCPR
🇧🇷Curitiba, PR, Brazil
Hospital Bruno Born
🇧🇷Lajeado, RS, Brazil
Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, RS, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital Universitario de Santa Maria
🇧🇷Santa Maria, RS, Brazil
Hospital Universitario Sao Francisco na Providencia na Deus
🇧🇷Bragança Paulista, Sao Paulo, Brazil
CiTen - Centro Hospital Municipal Antonio Giglio
🇧🇷Osasco, Sao Paulo, Brazil
Hospital Sao Jose
🇧🇷Criciúma, SC, Brazil
Hospital Regional Homero Miranda Gomes
🇧🇷São José, SC, Brazil
Hospital de Reabilitacao de Anomalias Craniofaciais
🇧🇷Bauru, SP, Brazil
UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu
🇧🇷Botucatu, SP, Brazil
IPECC
🇧🇷Campinas, SP, Brazil
Hospital Regional de Presidente Prudente
🇧🇷Presidente Prudente, SP, Brazil
Fundação Centro Médico de Campinas
🇧🇷Campinas, SP, Brazil
Hospital Estadual de Serrana
🇧🇷Ribeirão Preto, SP, Brazil
Santa Casa de Misericordia de Sao Paulo
🇧🇷São Paulo, SP, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
🇧🇷São Paulo, SP, Brazil
HCFMUSP
🇧🇷São Paulo, Brazil
Grand Prairie Regional Hospital
🇨🇦Grande Prairie, Alberta, Canada
East Kootenay Regional Hospital
🇨🇦Cranbrook, British Columbia, Canada
Nanaimo Regional General Hospital
🇨🇦Nanaimo, British Columbia, Canada
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Penticton Regional Hospital
🇨🇦Penticton, British Columbia, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Health Sciences Center Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
Grace General Hospital
🇨🇦Winnipeg, Manitoba, Canada
St. Boniface General Hospital
🇨🇦Winnipeg, Manitoba, Canada
Memorial University
🇨🇦Saint John's, Newfoundland and Labrador, Canada
Hamilton Health Sciences - Juravinski
🇨🇦Hamilton, Ontario, Canada
Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Markham Stouffville Hospital
🇨🇦Markham, Ontario, Canada
Hôpital Montfort
🇨🇦Ottawa, Ontario, Canada
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Niagara Health System - St Catharines Site
🇨🇦St. Catherines, Ontario, Canada
Health Sciences North Research Institute
🇨🇦Sudbury, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
University Health Network
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de Quebec - Hotel-Dieu de Levis
🇨🇦Lévis, Quebec, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Centre Hospitalier de l'université de Montréal (CHUM)
🇨🇦Montréal, Quebec, Canada
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
CHU de Quebec-University Laval
🇨🇦Québec, Quebec, Canada
Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ)
🇨🇦Québec, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke
🇨🇦Sherbrooke, Quebec, Canada
Regina General Hospital
🇨🇦Regina, Saskatchewan, Canada