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NCT05848713PHASE3Recruiting

AntiThrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia

University of Manitoba

Start Date

10/10/2023

Completion Date

3/31/2029

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Patients ≥18 years of age 2. Admitted to hospital for a suspected or confirmed diagnosis of CAP defined by: 1. Radiographic evidence of new or worsening infiltrate 2. 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 3. Requires supplemental oxygen to treat hypoxemia (or requires an increased level of supplemental oxygen if on chronic oxygen therapy) 4. Hospital admission anticipated to last ≥72 hours from randomization Exclusion Criteria: 1. Suspected or confirmed active COVID-19 infection 2. Hospital admission for \>72 hours prior to randomization 3. Patients receiving non-invasive or invasive ventilation, vasopressors, or extracorporeal life support (ECLS) within an ICU at the time of enrollment 4. Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization 5. Patients for whom the intent is to not use pharmacologic thromboprophylaxis 6. Patients with an independent indication for therapeutic-dose anticoagulation 7. Patients with a contraindication to therapeutic-dose anticoagulation, including: 1. Non-traumatic bleeding that requires medical evaluation or hospitalization within 30 days prior to CAP hospital admission 2. History of an inherited or acquired bleeding disorder 3. Cerebral aneurysm or mass lesions of the central nervous system 4. Ischemic stroke within 3 months of hospital admission 5. Gastrointestinal bleeding within 3 months of hospital admission 6. Platelet count \<50 x109/L OR INR \>2.0 OR hemoglobin \<80 g/L at the time of screening 7. Other physician-perceived contraindications to therapeutic anticoagulation 8. History of heparin induced thrombocytopenia (HIT) or other heparin allergy 9. Current or recent (within 7 days of screening) use of dual anti-platelet inhibitors (For example; Aspirin + one of the following; clopidogrel, ticagrelor, prasugrel) 10. Patients in whom imminent death is anticipated 11. Anticipated transfer to another hospital that is not a study site within 72 hours of randomization 12. Enrollment in other interventional trials related to anticoagulation or antiplatelet therapy during current hospitalization

Interventions

DRUG

Heparin

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Conditions

Community-acquired Pneumonia

Locations

University of Chicago

Chicago, Illinois 60637

United States

Ochsner Clinic

Jefferson, Louisiana 70121

United States

Maine Medical Centre

Portland, Maine 04102

United States

Henry Ford Health System

Dearborn, Michigan 48128

United States

Cooper University Health Care

Camden, New Jersey 08103

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Hospital Estadual Dr. Jayme Santos Neves

Serra, Espírito Santo 29166-828

Brazil

Hospital Evangelico de Vila Velha

Vila Velha, Espírito Santo

Brazil

Hospital Universitário Cassiano Antonio Moraes

Vitória, Espírito Santo

Brazil

Santa Casa de Misericordia de Itabuna

Itabuna, Estado de Bahia

Brazil

Hospital Brasilia

Brasília, Federal District

Brazil

Hospital Sao Brasilia

Brasília, Federal District

Brazil

Instituto de Cardiologia e Transplantes do Distrito Federal

Brasília, Federal District

Brazil

Hospital de Messejana Dr. Carlos Alberto Studart Gomes

Goiânia, Goiás

Brazil

Hospital Ruy Azeredo

Goiânia, Goiás

Brazil

Instituto Goiano de Oncologia e Hematologia - INGOH

Goiânia, Goiás

Brazil

Hospital Felicio Rocho

Belo Horizonte, Minas Gerais

Brazil

NUPEC-Orizonti

Belo Horizonte, Minas Gerais

Brazil

Hospital do Rocio

Campo Largo, Paraná 83606-177

Brazil

Hospital Santa Cruz

Curitiba, Paraná

Brazil

PUCPR

Curitiba, Paraná

Brazil

Hospital Bruno Born

Lajeado, Rio Grande do Sul

Brazil

Hospital Sao Vicente de Paulo

Passo Fundo, Rio Grande do Sul

Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul

Brazil

Hospital Universitario de Santa Maria

Santa Maria, Rio Grande do Sul

Brazil

Hospital Sao Jose

Criciúma, Santa Catarina

Brazil

Hospital Regional Homero Miranda Gomes

São José, South Carolina

Brazil

Hospital de Reabilitacao de Anomalias Craniofaciais

Bauru, São Paulo

Brazil

UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu

Botucatu, São Paulo

Brazil

Hospital Universitario Sao Francisco na Providencia na Deus

Bragança Paulista, São Paulo

Brazil

Fundação Centro Médico de Campinas

Campinas, São Paulo 13083-190

Brazil

IPECC

Campinas, São Paulo

Brazil

CiTen - Centro Hospital Municipal Antonio Giglio

Osasco, São Paulo

Brazil

Hospital Regional de Presidente Prudente

Presidente Prudente, São Paulo

Brazil

Hospital Estadual de Serrana

Ribeirão Preto, São Paulo

Brazil

Hospital Nipo-Brasileiro

São Paulo, São Paulo 02189-010

Brazil

HCFMUSP

São Paulo, São Paulo 05403-010

Brazil

Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo

Brazil

Santa Casa de Misericordia de Sao Paulo

São Paulo, São Paulo

Brazil

Foothills Medical Centre

Calgary, Alberta T2N 2T9

Canada

Grand Prairie Regional Hospital

Grande Prairie, Alberta T8V 4B1

Canada

Nanaimo Regional General Hospital

Nanaimo, British Columbia

Canada

Vancouver General Hospital

Vancouver, British Columbia V5Z 1M9

Canada

Health Sciences Center Winnipeg

Winnipeg, Manitoba R3A 1R9

Canada

Grace General Hospital

Winnipeg, Manitoba

Canada

St. Boniface General Hospital

Winnipeg, Manitoba

Canada

Memorial University

St. John's, Newfoundland and Labrador A1C 5S7

Canada

Health Sciences North Research Institute

Greater Sudbury, Ontario P3E 2H3

Canada

Hamilton Health Sciences - Juravinski

Hamilton, Ontario

Canada

Hamilton Health Sciences

Hamilton, Ontario

Canada

Markham Stouffville Hospital

Markham, Ontario L3P 7P3

Canada

Hôpital Montfort

Ottawa, Ontario

Canada

The Ottawa Hospital

Ottawa, Ontario

Canada

Niagara Health System - St Catharines Site

Saint Catherines, Ontario L2S 0A9

Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario M4N 3M5

Canada

University Health Network

Toronto, Ontario M5G2C4

Canada

Centre Hospitalier de Quebec - Hotel-Dieu de Levis

Lévis, Quebec G6V 3Z1

Canada

McGill University Health Centre

Montreal, Quebec H4A3J1

Canada

Centre Hospitalier de l'université de Montréal (CHUM)

Montreal, Quebec

Canada

Jewish General Hospital

Montreal, 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 S4P 0W5

Canada