Antithrombotic Therapy to Ameliorate Complications of COVID-19: The ATTACC Randomized Trial

Research title

Large scale randomised controlled trial to determine if daily treatment of anticoagulant heparin can improve the outcome of hospitalised COVID-19 patients

Summary

University Health Network in partnership with the University of Toronto, with funding from LifeArc, conducted a large, multicentre randomised control trial with 2,219  patients. The trial aimed to determine if the anticoagulant heparin, which is already on the market, may improve the outcome of COVID-19 patients. Small observational studies using heparin had shown it to be beneficial in treating COVID-19, however no controlled trials had been carried out on the drug.

Heparin had the potential to be beneficial due to its anti-coagulant properties, as severe infections of COVID-19 have been associated with the formation of blood clots in the lungs and other organs, also known as thrombosis.

Research organisation

University Health Network, University of Toronto

Researchers

Principal Investigators:

  • Professor Ewan Goligher, University Health Network, University of Toronto
  • Professor Patrick Lawler, University Health Network, University of Toronto
  • Professor Ryan Zarychanski, University of Manitoba

Potential of repurposed therapeutic for COVID-19 pandemic

Severe cases of COVID-19 are associated with the formation of blood clots in the lungs and other organs. This can affect both large and small blood vessels, blocking oxygen supply to the body and can result in death.

Heparin is widely used in hospitals as an anticoagulant, helping to prevent the formation of blood clots in at-risk patients. Several studies have also shown heparin to have anti-inflammatory properties which may help limit virus-induced inflammation. Whilst clinical benefits of heparin’s antiviral properties had not been determined, it had been shown to interfere with SARS-CoV-2 cell invasion in lab studies by interfering with viral attachment to cells.

LifeArc chose to focus funding on heparin because it is an inexpensive, highly accessible and widely-used generic drug that, if shown to work, could be available to patients much faster than any newly developed drug.

In evaluating the project for funding, LifeArc and the LifeArc COVID-19 Fund Scientific Advisory Board reviewed existing data from previous animal and safety studies. They also conducted due diligence and assessed the research plan. The successful researchers intended to conduct a multi-site adaptive clinical trial to determine if heparin could improve outcomes of hospitalised COVID-19 patients. The aim was to reduce the number who needed to be put on a ventilator or who die because of the infection. The clinical trial took place between April 2020 and January 2021 at multiple sites using the ATTACC Trial Network in Canada as well as sites in USA, Mexico, and Brazil.

Progress update

The findings of the ATTACC study, which formed part of a global multiplatform trial, highlighted some important points about treatment. Preliminary results, published in December 2020, showed that heparin was not effective in critically ill COVID-19 patients, and actually appeared to be harmful. However, in the same trial, full dose heparin in moderately ill Covid patients (i.e. not yet in intensive care) led to noticeably greater benefit compared to standard treatment.i In January 2021, results of the treatment among moderately ill patients (those not yet in intensive care) showed that full-dose heparin reduced the need for life support with improved survival compared to standard treatment.ii

Full results of the trial, which were published in August 2021 in the New England Journal of Medicine,iii,iv confirmed preliminary findings, and have changed clinical guidance for the treatment of COVID-19. This helped improve outcomes for patients admitted into hospital with the infection from around the world.