Full-dose blood thinners decreased need for life support for some covid 19 patients

Full dose anti-coagulation (blood thinner) treatments given to moderately ill patients hospitalized for COVID-19 reduced the requirement of vital organ support in a large clinical trial conducted worldwide. A trend in possible reduction of mortality was also observed and is being further studied. With large numbers of COVID-19 patients requiring hospitalization, these outcomes could also help reduce the overload on intensive care units around the world.

Three clinical trial platforms spanning five continents in more than 300 hospitals have been working together to test whether there is a greater benefit of full doses of heparin (blood thinners) to treat moderately ill hospitalized adults with COVID-19 compared to the lower heparin dose typically administered to prevent blood clots in hospitalized patients. Moderately ill patients are those not in intensive care and who did not receive organ support such as mechanical ventilation at trial enrollment.

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Based on the interim results of more than 1000 moderately ill patients admitted to hospital, findings showed that full doses of blood thinners, in addition to being safe, were superior to the doses normally given to prevent blood clots in hospitalized patients. The trial investigators are now working as fast as possible to make the full results of the study available so clinicians can make informed decisions about treating their COVID-19 patients.

As is normal for clinical trials, these trials are overseen by independent boards that routinely review the data and are composed of experts in ethics, biostatistics, clinical trials, and blood clotting disorders. Informed by the deliberations of these oversight boards, all the trial sites have stopped enrollment. 

However, research questions remain about how to further improve the clinical care of COVID-19 patients.  This adaptive protocol has been designed to allow different drugs to be started, stopped or combined during the study in response to emerging scientific data. This approach enables the rapid testing of additional agents without compromising safety and the study will evolve accordingly.  

The trial results reported today complement the group’s findings announced in December that routine use of full-dose anti-coagulation when started in the ICU in critically ill COVID-19 patients was not beneficial and may have been  harmful in some patients.  

“In a disease with a limited number of effective therapies, our results represent a game-changer that will impact practice for moderately ill hospitalized COVID-19 patients around the world,” said Ryan Zarychanski, MD, M.Sc., associate professor, hematologist and critical care physician at the University of Manitoba and CancerCare Manitoba, Canada, and chair of the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) platform and of the therapeutic anticoagulation domain of the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

Early in the pandemic, physicians around the world observed increased rates of blood clots and inflammation among COVID-19 patients which affected multiple organs and led to complications such as lung failure, heart attack and stroke. Whether providing increased doses of blood thinners routinely administered to hospitalized patients would be safe and effective was unknown at that time.

“These results are very exciting and lead us to better understand the impact of applying the right therapies at the right time in the course of this challenging disease,” said Judith Hochman, MD, chair of Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4a) platform, the Harold Snyder Family Professor & Associate Director of Cardiology, Senior Associate Dean for Clinical Sciences and Co-Director, NYU-HHC Clinical and Translational Science Institute, NYU Grossman School of Medicine. 

“These are the first multi-platform international clinical trials ever undertaken and given the rapid discovery of Heparin’s positive impact on  patient outcomes  during the middle of the deadly COVID-19 pandemic, I don’t think it will be the last time researchers, clinicians and patients join forces across continents to test potential treatments against any number of diseases,” said Patrick Lawler, MD, MPH cardiologist at the University of Toronto and Peter Munk Cardiac Centre at University Health Network, who was co-principal investigator of ATTACC and a member of the international trial steering committee for REMAP-CAP.

“Early on in the pandemic we observed substantial prevalence of clotting in hospitalized Covid19 patients, that caused severe complications,” said Jeffrey Berger MD, ACTIV-4a co-PI, associate Professor of Medicine and Surgery, and Director of the Center for the Prevention of Cardiovascular Diseases at NYU Grossman School of Medicine. “It is remarkable to lead a clinical trial that proves early intervention targeted clotting can improve outcomes and avoid many complications associated with Covid19.”

Three international partners have come together in an unprecedented collaboration resulting in a multiple platform randomized controlled trial. The three international trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAPexternal link) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4a (ACTIV-4a) Antithrombotics Inpatient;  and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACCexternal link). The trials which span four continents have the common goal of assessing the benefit of full doses of blood thinners to treat moderately ill or critically ill adults hospitalized for COVID-19, compared to a lower dose often used to prevent blood clots in hospitalized patients. To meet the challenge of this pandemic, investigators worldwide joined forces to answer this question as rapidly as possible. In the United States, the ACTIV-4a trial is being led by a collaborative effort with several universities, including the University of Pittsburgh and New York University Grossman School of Medicine, New York City. 

The trials are supported by multiple international funding organizations including Canadian Institutes of Health Research (CAN), the LifeArc Foundation, the NIH National Heart, Lung & Blood Institute (US), National Institutes of Health Research (UK), National Health and Medical Research Council (AUS) and the PREPARE and RECOVER consortia (EU).