NIH ACTIV initiative launches adaptive clinical trials of blood-clotting treatments for COVID-19.- BMS + Pfizer

The National Institutes of Health has launched two of three adaptive Phase III clinical trials evaluating the safety and effectiveness of varying types of blood thinners to treat adults diagnosed with COVID-19. Part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, these trials will be conducted at more than 100 sites around the world and will involve patients in various clinical settings — those who have not been hospitalized, those currently hospitalized and those discharged after hospitalization for moderate to severe disease. Collectively known as ACTIV-4 Antithrombotics, the trials will provide critical insights that could help guide the care of patients with COVID-19, particularly those who suffer from life-threatening blood clots. The trial for hospitalized COVID-19 patients and the trial for patients with COVID-19 who have not been hospitalized are now underway. A third trial to start later will focus on patients discharged after hospitalization for moderate to severe COVID-19 disease. All three clinical trials will be coordinated and overseen by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, and funded through Operation Warp Speed. Researchers have noted that many patients who have died from COVID-19 — the deadly disease caused by SARS-CoV-2 — had formed blood clots throughout their bodies, including in their smallest blood vessels. This unusual clotting, one of many life-threatening effects of the disease, has caused multiple health complications, from organ damage to heart attack, stroke and pulmonary embolism. ACTIV-4 Antithrombotics will be recruiting at sites with significant COVID-19 burden and are interested in enrolling patients in studies testing potential treatments to prevent or reduce the formation of blood clots. The adaptive design of the protocol allows different blood thinners to be started, stopped or combined during the study in response to emerging trial data. This approach accelerates the timeline for testing different agents without compromising safety. An observational, 2,773-patient study researchers from the Icahn School of Medicine at Mount Sinai published in the Journal of the American College of Cardiology in July suggested anticoagulant drugs might help, at least in people who are hospitalized with the disease. But no definitive evidence exists to support their use. It's also unclear which types of patients would benefit most, when they should be treated, which drug they should get or how high of a dose. Hospitalized patients will receive either a low or high dose of the generic drug heparin, with the goal of preventing or reducing the formation of clots. Non-hospitalized patients will get a placebo, Aspirin or a low dose of the Bristol Myers and Pfizer blood thinner Eliquis. Researchers will assess whether such treatment can reduce the instance of life-threatening heart or lung problems. Discharged patients will get an unspecified blood thinner with the hope of lowering the risk of a heart attack, stroke, or other complication within 45 days of leaving the hospital. See- Journal of the American College of Cardiology.Volume 76, Issue 1, July 2020. DOI: 10.1016/j.jacc.2020.05.001 "Association of Treatment Dose Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19"--Ishan Paranjpe, Valentin Fuster, Anuradha Lala, Adam J. Russak, Benjamin S. Glicksberg, Matthew A. Levin, Alexander W. Charney, Jagat Narula, Zahi A. Fayad, Emilia Bagiella, Shan Zhao and Girish N. Nadkarni.