Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC)

Completed · Phase 2/Phase 3

Conditions studied: COVID-19, Pneumonia

In brief

Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host inflammatory response and activation of coagulation pathways. Macro- and micro-vascular thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic, anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive randomized controlled trial will determine whether therapeutic anticoagulation with heparin (subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus usual care reduces the need for intubation or death in hospitalized patients with COVID-19. The trial uses an adaptive design which was chosen to overcome limitations in available data to inform a priori estimation of event rates and possible effect sizes. The adaptive design also includes response-adaptive randomization based on baseline D-dimer level, probing for differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian adaptive randomized trial will stop at a conclusion 1) when the posterior probability that the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when the posterior probability that the proportional odds ratio is greater than 1.2 is less than 10% (definition of futility) or; 3) when the posterior probability that the proportional odds ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a maximum of 3,000 patients, although in many simulations the trial may require fewer patients. The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to accelerate evidence generation.

Key facts

Study ID

NCT04372589

Run by

University of Manitoba

People needed

1200

Starts

2020-05-20

Expected to finish

2021-05-17

Last updated by the study team

2021-07-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients ≥18 years of age providing (possibly through a substitute decision maker) informed consent who require hospitalization anticipated to last ≥72 hours, for microbiologically-confirmed COVID-19, enrolled < 72 hours of hospital admission or of COVID-19 confirmation
• If the patient is already hospitalized and the COVID-19 diagnosis is due to an outbreak or an incidental finding, then enrollment can occur within 72 hours of a clinical syndrome attributable to COVID-19 that requires continued hospitalization (e.g. new or worsening oxygen requirements or acute kidney injury) which is further anticipated to extend the hospital admission by an additional 72 hours from randomization.

You may not qualify if…

• Patients admitted to an ICU AND receiving organ support (i.e. high flow nasal oxygen, receiving non-invasive or invasive mechanical ventilation, or are requiring vasopressor/inotrope)
• Patients for whom the intent is to not use pharmacologic thromboprophylaxis
• Active bleeding
• Risk factors for bleeding, including:
• intracranial surgery or stroke within 3 months;
• history of intracerebral arteriovenous malformation;
• cerebral aneurysm or mass lesions of the central nervous system;
• intracranial malignancy
• history of intracranial bleeding
• history of bleeding diatheses (e.g., hemophilia)
• history of gastrointestinal bleeding within previous 3 months
• thrombolysis within the previous 7 days
• presence of an epidural or spinal catheter
• recent major surgery <14 days
• uncontrolled hypertension (sBP >200 mmHg, dBP >120 mmHg)
• other physician-perceived contraindications to anticoagulation
• Platelet count <50 x10\^9/L, INR >2.0, or baseline aPTT >50 (if available per SOC testing)
• Hemoglobin <80 g/L (to minimize the likelihood of requiring red blood cell transfusion if potential bleeding were to occur)
• Acute or subacute bacterial endocarditis
• History of heparin induced thrombocytopenia (HIT) or other heparin allergy including hypersensitivity
• Current use of dual antiplatelet therapy
• Patients with an independent indication for therapeutic anticoagulation
• Patients in whom imminent demise is anticipated and there is no commitment to active ongoing intervention
• Anticipated transfer to another hospital that is not a study site within 72 hours
• Enrollment in other trials related to anticoagulation or antiplatelet therapy

Where it is running

• University of Chicago — Chicago, Illinois, United States
• Ochsner Clinic — Jefferson, Louisiana, United States
• Maine Medical Center — Portland, Maine, United States
• Henry Ford University — Dearborn, Michigan, United States
• Beaumont Hospital — Royal Oak, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Saint Louis University School of Medicine/Saint Louis Veterans Affairs Medical Center — St Louis, Missouri, United States
• Cooper University Health Care — Camden, New Jersey, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Saint Barnabas Medical Center — Livingston, New Jersey, United States
• Montefiore-Einstein Center for Heart and Vascular Care — New York, New York, United States
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• Hospital Unimed do Cariri — Juazeiro do Norte, Ceará, Brazil
• Santa Casa de Misericordia de Itabuna — Itabuna, Estado de Bahia, Brazil
• Instituto Goiano de Oncologia e Hematologia - INGOH — Goiânia, Goiás, Brazil
• Centro de Pesquisas Clínicas Humap - UFMS — Campo Grande, Mato Grosso do Sul, Brazil
• Clinica de Campo Grande S/A — Campo Grande, Mato Grosso do Sul, Brazil
• Unimed Campo Grande — Campo Grande, Mato Grosso do Sul, Brazil
• Hospital Felício Rocho — Belo Horizonte, Minas Gerais, Brazil
• Hospital das Clinicas da UFPR — Curitiba, Paraná, Brazil
• Pontifícia Universidade Católica do Paraná — Curitiba, Paraná, Brazil
• Parana Medical Research Center — Maringá, Paraná, Brazil
• Hospital Agamenon Magalhaes — Recife, Pernanbuco, Brazil
• Hospital Universitario Pedro Ernesto — Rio de Janeiro, Rio de Janeiro, Brazil
• Emory University Hospital Midtown — Atlanta, Georgia, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.