News Release

Tuesday, December 22, 2020

NIH ACTIV Trial of blood thinners pauses enrollment of critically ill COVID-19 patients

Three clinical trial platforms working together to test the effects of full doses of anticoagulants (blood thinners) in COVID-19 patients have pausedÌýenrollmentÌýfor one group of patients. Among critically ill COVID-19 patients requiring intensive care unit (ICU) support, therapeutic anticoagulation drugs did not reduce the need for organ support.ÌýEnrollmentÌýcontinuesÌýfor moderately ill hospitalized COVID-19 patientsÌýin the trials.Ìý

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.ÌýInformed by the deliberations of these oversight boards, all the trial sitesÌýhave paused enrollment of the most critically ill hospitalized patients with COVID-19.ÌýA potential for harm in this sub-group could not be excluded. Increased bleeding is a known complication of full-dose anticoagulation.ÌýThe trials are working urgently to undertake additional analyses which will be made available as soon as possible.ÌýÌýÌý

At the recommendation of the oversight boards,Ìýpatients who do not require ICU care at the time of enrollment will continue to be enrolled in the trial. Whether the use of full-dose compared to low-dose blood thinners leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very importantÌýquestion. Patients who require full-dose blood thinners for another medical indication are not included in these trials.

COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, heart attack, and stroke.Ìý

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 () Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4)ÌýAntithromboticsÌýInpatient;Ìý and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (). 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.ÌýIn the United States, the ACTIV-4 trial is being led by a collaborative effort with several universities, including the University of Pittsburgh and New York University, New York City.ÌýÌýÌý

The trials are supported by multiple international funding organizations including the Canadian Institutes of Health Research, the National Institute for Health Research (U.K.), the National Health and Medical Research Council (Australia), the ľ¹ÏÖ±²¥ (U.S.), and the PREPARE and RECOVER consortia (EU).Ìý

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit .Ìý

About the ľ¹ÏÖ±²¥ (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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