MedPath

AntiThrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia

Phase 3
Recruiting
Conditions
Community-acquired Pneumonia
Interventions
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
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

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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

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Therapeutic-Dose HeparinHeparinParticipants 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
NameTimeMethod
Ordinal endpoint reflecting survival30 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
NameTimeMethod
Hospital-free days30 days, 90 days, and 180 days

Days alive outside hospital

Health related quality of life30 days, 90 days, and 180 days

Using the Clinical Frailty Scale instrument

Bleeding events14 days

Number of participants with major bleeds as defined by the ISTH definition.

HIT events14 days

Number of participants with laboratory confirmed heparin induced thrombocytopenia (HIT)

Thrombotic events30 days and 90 days

Number of participants with deep vein thrombosis, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke

Invasive mechanical ventilation30 days

Ordered categorical endpoint with three possible outcomes based on the worst status of each patient through day 30 following randomization

All cause mortality30 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

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