- The National Institutes of Health has begun two of three planned Phase 3 trials meant to definitively test whether blood-thinning drugs can help improve health outcomes in patients with COVID-19.
- The program, known as ACTIV-4 Antithrombotics, will test whether heparin and other blood thinners can help severely ill COVID-19 patients as well as those with more mild disease or who have been discharged from the hospital. Bristol Myers Squibb and Pfizer will donate Eliquis and Aspirin to the effort, but other medications could eventually be tested as well.
- As its name suggests, ACTIV-4 is the fourth large trial program launched by the Accelerating COVID-19 Therapeutic Interventions and Vaccines, or ACTIV, initiative, a partnership between the NIH and 16 drugmakers. Other studies are testing the use of engineered antibodies and immune-modulating drugs in COVID-19, though they have yet to produce results.
In the early stages of the coronavirus pandemic, biopharma companies and regulators formed unusual collaborations in an effort to pick the best possible drugs to test against COVID-19 and speed them forward.
The Bill & Melinda Gates Foundation and Wellcome joined with others to form the COVID-19 Therapeutics Accelerator. Pharmaceutical companies, biotechs and venture firms created the "COVID R&D" consortium. Sanofi and GlaxoSmithKline, two rivals, teamed up to develop a coronavirus vaccine that is now in early testing. Each partnership was established to cut down on duplicative work and move treatments through testing faster than otherwise would be possible.
The ACTIV partnership, formed in April, is the most sprawling example, combining the efforts of 16 drugmakers, two regulatory agencies, the NIH and other government offices. It's forming "master protocols" for trials that evaluate multiple drugs simultaneously and adapt their design, so investigators can weed out treatments that aren't working and focus on ones that appear beneficial.
Before Thursday, three programs had emerged from the initiative. The first is testing various immuno-modulating drugs, like Eli Lilly's Olumiant, on top of Gilead's antiviral Veklury, one of the only treatments the Food and Drug Administration has cleared for emergency use against COVID-19. The second and third programs, started in August, each evaluate the use of engineered antibody drugs in patients with mild, moderate or severe COVID-19. None of them have produced results yet.
ACTIV-4, meanwhile, has been launched in response to findings from researchers that many patients who have died from COVID-19 have had blood clots form throughout their bodies, even in the tiniest blood vessels. These cases have been seen even among younger patients, and the clots have led to strokes, heart attacks and other potentially fatal complications.
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.
ACTIV-4 aims to solve that problem. It consists of three trials — one in hospitalized COVID-19 patients, a second in patients who don't need to be hospitalized and a third in people who have been discharged. More than 100 trial sites across the globe will be involved.
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.
Investigators may stop the use of some of those drugs, however, or combine different treatments as the study progresses. They will also collect blood samples to try to find clues as to who might be at risk of complications from the disease.
"There is currently no standard of care for anticoagulation in hospitalized COVID-19 patients, and there is a desperate need for clinical evidence to guide practice," NIH Director Francis Collins said in a statement.
The trial in COVID-19 patients who have been discharged is the only one that hasn't started yet. The NIH said that study would begin "later," but wasn't specific.