AntiThrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia

Phase 3

Recruiting

• Conditions: Community-acquired Pneumonia
• Interventions: Drug: Heparin

• 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.

Study Timeline

• Study First Submitted: 2023-04-17
• Study First Submitted QC: 2023-04-28
• Study First Posted: 2023-05-08
• Study Start: 2023-10-10
• Status Verified: 2025-01
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-14
• Primary Completion: 2028-03-31
• Study Completion: 2029-03-31

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

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

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 (62)

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

Scroll for more (52 remaining)