AntiThrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia (ATTACC-CAP)

February 15, 2024 updated by: University of Manitoba
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

4000

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • BA
      • Itabuna, BA, Brazil
        • Recruiting
        • Santa Casa de Misericordia de Itabuna
        • Contact:
          • Eduardo Kowalski, MD
        • Principal Investigator:
          • Eduardo Kowalski, MD
    • DF
      • Brasília, DF, Brazil
        • Not yet recruiting
        • Hospital Brasilia
        • Contact:
          • Marina da Silva, MD
        • Principal Investigator:
          • Marina da Silva, MD
      • Brasília, DF, Brazil
        • Not yet recruiting
        • Hospital Sao Brasilia
        • Contact:
          • Mauricio Pompilio, MD
        • Principal Investigator:
          • Mauricio Pompilio, MD
      • Brasília, DF, Brazil
        • Active, not recruiting
        • Instituto de Cardiologia e Transplantes do Distrito Federal
    • ES
      • Vila Velha, ES, Brazil
        • Recruiting
        • Hospital Evangélico de Vila Velha
        • Contact:
          • Joao Moraes Junior, MD
        • Principal Investigator:
          • Joao Moraes Junior, MD
      • Vitória, ES, Brazil
        • Not yet recruiting
        • Hospital Universitario Cassiano Antonio Moraes
        • Contact:
          • Felipe Vieira, MD
        • Principal Investigator:
          • Felipe Vieira, MD
    • GO
      • Goiania, GO, Brazil
        • Recruiting
        • Instituto Goiano de Oncologia e Hematologia - INGOH
        • Contact:
          • Mayler Santos, MD
        • Principal Investigator:
          • Mayler Santos, MD
      • Goiânia, GO, Brazil
        • Not yet recruiting
        • Hospital de Messejana Dr. Carlos Alberto Studart Gomes
        • Contact:
          • Sandra Nivea dos Reis Saraiva, MD
        • Principal Investigator:
          • Sandra Navea do Reis Saraiva, MD
      • Goiânia, GO, Brazil
        • Not yet recruiting
        • Hospital Ruy Azeredo
        • Contact:
          • Rafael Bastos, MD
        • Principal Investigator:
          • Rafael Bastos, MD
    • MG
      • Belo Horizonte, MG, Brazil
        • Recruiting
        • Hospital Felício Rocho
        • Contact:
          • Ana Carolina Procopio
        • Principal Investigator:
          • Ana Carolina Procopio, MD
      • Belo Horizonte, MG, Brazil
        • Not yet recruiting
        • NUPEC-Orizonti
        • Contact:
          • Fernando Neuenschwander, MD
        • Principal Investigator:
          • Fernando Neuenschwander, MD
    • MS
      • Campo Grande, MS, Brazil
        • Recruiting
        • Hospital do Coração - MS
        • Contact:
          • Mauricio Pompilio, MD
        • Principal Investigator:
          • Mauricio Pompilio, MD
    • PR
      • Curitiba, PR, Brazil
        • Recruiting
        • Hospital Santa Cruz
        • Contact:
          • Marcelo Carneiro, MD
        • Principal Investigator:
          • Marcelo Carneiro, MD
      • Curitiba, PR, Brazil
        • Recruiting
        • PUCPR
        • Contact:
          • Jose Ribas Fortes, MD
        • Principal Investigator:
          • Jose Ribas Forte, MD
    • RS
      • Lajeado, RS, Brazil
        • Not yet recruiting
        • Hospital Bruno Born
        • Contact:
          • Lucas Mallmann, MD
        • Principal Investigator:
          • Lucas Mallmann, MD
      • Passo Fundo, RS, Brazil
        • Recruiting
        • Hospital São Vicente de Paulo
        • Contact:
          • Alexandre Tognon, MD
        • Principal Investigator:
          • Alexandre Tognon
      • Porto Alegre, RS, Brazil
        • Not yet recruiting
        • Hospital de Clínicas de Porto Alegre
        • Contact:
          • Paulo Dalcin, MD
        • Principal Investigator:
          • Paulo Dalcin, MD
      • Santa Maria, RS, Brazil
        • Not yet recruiting
        • Hospital Universitário de Santa Maria
        • Contact:
          • Ariovaldo Fagudes, MD
        • Principal Investigator:
          • Ariovaldo Fagudes, MD
    • SC
      • Criciúma, SC, Brazil
        • Recruiting
        • Hospital Sao Jose
        • Contact:
          • Felipe Pizzol, MD
        • Principal Investigator:
          • Felipe Pizzol, MD
      • São José, SC, Brazil
        • Recruiting
        • Hospital Regional Homero Miranda Gomes
        • Contact:
          • Bruno Kroeff Bergesch, MD
        • Principal Investigator:
          • Bruno Kroeff Bergesch, MD
    • SP
      • Bauru, SP, Brazil
        • Not yet recruiting
        • Hospital de Reabilitacao de Anomalias Craniofaciais
        • Contact:
          • Lucas Soler, MD
        • Principal Investigator:
          • Lucas Soler, MD
      • Botucatu, SP, Brazil
        • Recruiting
        • UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu
        • Contact:
          • Suzana Erico Tanni, MD
        • Principal Investigator:
          • Suzana Erico Tanni, MD
      • Campinas, SP, Brazil
        • Recruiting
        • IPECC
        • Contact:
          • Jose Francisco Kerr Saraiva, MD
        • Principal Investigator:
          • Jose Francisco Kerr Saraiva, MD
      • Presidente Prudente, SP, Brazil
        • Not yet recruiting
        • Hospital Regional de Presidente Prudente
        • Contact:
          • Luis Felipe Pires, MD
        • Principal Investigator:
          • Luis Felipe Pires, MD
      • Ribeirão Preto, SP, Brazil
        • Not yet recruiting
        • Hospital Estadual de Serrana
        • Contact:
          • Marcos Borges, MD
        • Principal Investigator:
          • Marcos Borges, MD
      • São Paulo, SP, Brazil
        • Not yet recruiting
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
        • Contact:
          • Julio Alencar, MD
        • Principal Investigator:
          • Julio Alencar, MD
      • São Paulo, SP, Brazil
        • Not yet recruiting
        • Santa Casa de Misericordia de Sao Paulo
        • Contact:
          • Ricardo Chinarelli, MD
        • Principal Investigator:
          • Ricardo Chinarelli, MD
    • Sao Paulo
      • Bragança Paulista, Sao Paulo, Brazil
        • Recruiting
        • Hospital Universitario Sao Francisco na Providencia na Deus
        • Contact:
          • Gustavo Mamprin, MD
        • Principal Investigator:
          • Gustavo Mamprin, MD
      • Osasco, Sao Paulo, Brazil
        • Recruiting
        • CiTen - Centro Hospital Municipal Antonio Giglio
        • Contact:
          • Enrico Fortunato, MD
        • Principal Investigator:
          • Enrico Fortunato, MD
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Not yet recruiting
        • Foothills Medical Centre
        • Contact:
        • Principal Investigator:
          • Deepa Suryanarayan, MD
    • British Columbia
      • Nanaimo, British Columbia, Canada
        • Not yet recruiting
        • Nanaimo Regional General Hospital
        • Contact:
          • Alistair Teale, MD
        • Principal Investigator:
          • Alistair Teale, MD
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Not yet recruiting
        • Vancouver General Hospital
        • Principal Investigator:
          • Ted Steiner, MD
        • Contact:
          • Ted Steiner, MD
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Recruiting
        • St. Boniface General Hospital
        • Contact:
          • Vi Dao, MD
        • Principal Investigator:
          • Terry Wuerz, MD
        • Principal Investigator:
          • Vi Dao, MD
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Recruiting
        • Health Sciences Center Winnipeg
        • Contact:
          • Brett Houstin, MD
      • Winnipeg, Manitoba, Canada
        • Recruiting
        • Grace General Hospital
        • Contact:
        • Principal Investigator:
          • Sylvain Lother, MD
    • Newfoundland and Labrador
      • Saint John's, Newfoundland and Labrador, Canada, A1C 5S7
        • Not yet recruiting
        • Memorial University
        • Contact:
          • Peter Daley, MD
        • Principal Investigator:
          • Peter Daley, MD
    • Ontario
      • Hamilton, Ontario, Canada
        • Not yet recruiting
        • Hamilton Health Sciences
        • Contact:
          • Alison Fox-Robichaud, MD
        • Principal Investigator:
          • Alison Fox-Robichaud, MD
      • Hamilton, Ontario, Canada
        • Not yet recruiting
        • Hamilton Health Sciences - Juravinski
        • Principal Investigator:
          • Dominik Mertz, MD
        • Principal Investigator:
          • Bram Rochwerg, MD
        • Contact:
          • Bram Rochwerg, MD
      • Kingston, Ontario, Canada, K7L 2V7
        • Not yet recruiting
        • Kingston General Hospital
        • Contact:
          • Barbara Antuna-Puente
        • Principal Investigator:
          • Santiago Perez-Patrigeon, MD
      • Markham, Ontario, Canada, L3P 7P3
        • Not yet recruiting
        • Markham Stouffville Hospital
        • Principal Investigator:
          • Paul Lee, MD
        • Contact:
          • Paul Lee, MD
        • Principal Investigator:
          • Janet Nguyen, MD
      • Ottawa, Ontario, Canada
        • Not yet recruiting
        • The Ottawa Hospital
        • Contact:
          • Lana Castellucci, MD
      • Ottawa, Ontario, Canada
        • Not yet recruiting
        • Hôpital Montfort
        • Contact:
          • Marc Carrier, MD
      • St. Catherines, Ontario, Canada, L2S 0A9
      • Toronto, Ontario, Canada, M4N 3M5
        • Not yet recruiting
        • Sunnybrook Health Sciences Centre
        • Contact:
          • Jonathan Zipursky, MD
        • Principal Investigator:
          • Jonathan Zipursky, MD
      • Toronto, Ontario, Canada, M5G2C4
        • Not yet recruiting
        • University Health Network
        • Principal Investigator:
          • Jameel Abdulrehman, MD
        • Contact:
          • Jameel Abdulrehman, MD
    • Quebec
      • Montréal, Quebec, Canada
        • Not yet recruiting
        • Jewish General Hospital
        • Contact:
          • Susan Khan, MD
        • Contact:
          • Vicky Tagalakis, MD
      • Montréal, Quebec, Canada, H4A3J1
        • Not yet recruiting
        • McGill University Health Centre
        • Contact:
          • Emily Gibson McDonald, MD, MSc
      • Montréal, Quebec, Canada
        • Not yet recruiting
        • Centre Hospitalier de l'Université de Montréal (CHUM)
        • Contact:
          • Emmanuelle Duceppe, MD
      • Québec, Quebec, Canada
        • Recruiting
        • Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ)
        • Contact:
          • Francois Lallouche, MD
      • Québec, Quebec, Canada
        • Recruiting
        • CHU de Quebec-University Laval
        • Contact:
          • Alexis Turgeon, MD, MSc
      • Sherbrooke, Quebec, Canada
        • Not yet recruiting
        • Centre Hospitalier Universitaire de Sherbrooke
        • Principal Investigator:
          • Francois Lamontagne, MD
        • Contact:
          • Francois Lamontagne, MD
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Not yet recruiting
        • University of Chicago
        • Contact:
          • Jonathan Paul, MD
    • Louisiana
      • Jefferson, Louisiana, United States, 70121
        • Not yet recruiting
        • Ochsner Clinic
        • Contact:
          • Mark Effron, MD
    • Maine
      • Portland, Maine, United States, 04102
        • Not yet recruiting
        • Maine Medical Center
        • Contact:
          • Daniel Meyer, MD
      • Portland, Maine, United States, 04102
        • Not yet recruiting
        • Maine Medical Centre
        • Contact:
          • Daniel Meyer, MD
        • Principal Investigator:
          • Daniel Meyer, MD
    • Michigan
      • Dearborn, Michigan, United States, 48128
        • Recruiting
        • Henry Ford University
        • Contact:
          • Scott Kaatz, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Therapeutic-Dose 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.
Drug: Heparin

Preference is for LMWH given ease of administration and possibility of a more favorable safety profile, if no contraindication is present. Enoxaparin, dalteparin, or tinzaparin are acceptable LMWHs to be used for patients in the investigational arm and dose should be based on measured or estimated weight of the patient.

Alternatively, intravenous UFH may be used and may be preferred in the presence of significant renal compromise. Intravenous UFH is typically dosed according to total body weight and pragmatically adjusted according to local institutional policy to achieve an activated partial thromboplastin time (aPTT) of 1.5-2.5x the reference value, or a corresponding UFH anti-Xa level. If UFH is used, the availability of a local site policy that specifies an aPTT target in this range or a corresponding anti-Xa value is a requirement.
No Intervention: Usual Care
Participants randomized to the control arm will receive usual care thromboprophylactic dose anticoagulation according to local practice. To ensure adequate separation between the study groups, the dose of heparin/LMWH used in the usual care arm should not equal more than half of the approved therapeutic dose for that agent according to local VTE treatment protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ordinal endpoint reflecting survival
Time Frame: 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.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bleeding events
Time Frame: 14 days
Number of participants with major bleeds as defined by the ISTH definition.
14 days
HIT events
Time Frame: 14 days
Number of participants with laboratory confirmed heparin induced thrombocytopenia (HIT)
14 days
Thrombotic events
Time Frame: 30 days and 90 days
Number of participants with deep vein thrombosis, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke
30 days and 90 days
Invasive mechanical ventilation
Time Frame: 30 days
Ordered categorical endpoint with three possible outcomes based on the worst status of each patient through day 30 following randomization
30 days
All cause mortality
Time Frame: 30 days, 90 days, and 180 days
30 days, 90 days, and 180 days
Hospital-free days
Time Frame: 30 days, 90 days, and 180 days
Days alive outside hospital
30 days, 90 days, and 180 days
Health related quality of life
Time Frame: 30 days, 90 days, and 180 days
Using the EQ-5D-5L instrument
30 days, 90 days, and 180 days
Health related quality of life
Time Frame: 30 days, 90 days, and 180 days
Using the Clinical Frailty Scale instrument
30 days, 90 days, and 180 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Collaborators

Canadian Institutes of Health Research (CIHR)
Ozmosis Research Inc.
Canadian Critical Care Trials Group
Research Manitoba
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

Investigators

  • Principal Investigator: Patrick Lawler, MD, University Health Network and McGill University
  • Principal Investigator: Sylvain Lother, MD, University of Manitoba
  • Principal Investigator: Alexis Turgeon, MD, L'Universite Laval
  • Principal Investigator: Ryan Zarychanski, MD, University of Manitoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2023

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

April 17, 2023

First Submitted That Met QC Criteria

April 28, 2023

First Posted (Actual)

May 8, 2023

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 15, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATTACC-CAP
  • OZM-129 (Other Identifier: Ozmosis Research Inc.)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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