Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.
The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.
The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.
The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.
Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19.
Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.
“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.
Patients who require full dose anticoagulants for another medical indication are not included in these trials.
The statement explains that 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,, and .
The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for( ) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 ( 4) Antithrombotics Inpatient; 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 anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.
In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.
The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).
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