Health Canada, U.S. FDA and European Medical Agency cite findings from AcT Trial for regulatory approval of new use for a known drug
It was the largest acute stroke clinical trial ever run in Canada, and now findings have changed drug-treatment guidelines for ischemic stroke worldwide.
"In 30 years, this is the first time we’re having an acute stroke drug approved by the FDA," says Dr. Bijoy Menon, MSc’15, MD, a professor at the University of Calgary, neurologist at the Foothills Medical Centre (FMC), and principal investigator on the AcT Trial. "This is a first for the university. And the effort to change practice for the better is the Calgary Stroke Program ’s way of delivering on what our patients want."
Findings published in The Lancet in 2022 demonstrated that Tenecteplase (TNK) - a safe, well-tolerated drug commonly used as a clot buster for heart attacks - was an effective treatment for acute ischemic stroke. Ischemic stroke is caused by a sudden blockage of an artery to the brain that deprives it of critical nutrients, such as glucose and oxygen.
"Tenecteplase is known to be an effective clot-dissolving drug. It is very easy to administer, which makes it a game changer when seconds count to save brain cells," says Menon.
The other drug tested in the trial, Alteplase, was more complex to administer. It took up to an hour to administer and required an infusion pump, which was cumbersome when transporting patients.
After the AcT Trial was published, many centres started using TNK as a stroke treatment before regulatory approval, a process known as using a drug "off label." But, to permanently shift global practice and ensure broad access to this life-altering treatment, formal regulatory approval was essential.
The U.S. Food and Drug Administration (FDA), regarded as a highly-rigorous regulator, was not content with just reviewing the paper. It sent representatives to confirm the impressive research done at UCalgary.
"They want to see the data for themselves," says Menon.
Calgary Stroke Program AcT Trial data scrutinized
A team from the FDA visited Calgary for a week on two separate occasions, and a team of inspectors put the stroke team under the microscope. They commandeered an office in the Department of Clinical Neurosciences at the FMC and started poring over the trial’s results.
It was not a relaxing week, says Carol Kenney, RN, clinical trials co-ordinator for the Calgary Stroke Program. "I didn’t sleep all week."
During the first visit, Kenney says, the inspectors focused on patient safety and serious adverse events collected during the study. The second visit was to scrutinize the stroke team’s work as a sponsor of the trial.
The inspectors needed to be close to the stroke team, so they set up shop on the 11th floor of Foothills Hospital.
"They needed their own office," Kenney says. "If they had to leave, they had to lock up their equipment."
Members of the stroke team, including data manager Qiao Zhang, and Stroke Trials Operations group lead Craig Doram, BSc (Eng)’08, were individually interviewed about the trial, and requests for supporting data arrived each morning.
"Basically, it was our job to sit with them and answer questions," says Kenney
The European Medical Agency had followed a similar process a year before and approved the drug’s new use. The FDA and Health Canada have now both followed suit.
"They go through everything. They check everything. (The success in the audit) is a testament to the quality of our team and the focus on patient safety the Calgary Stroke Program has," says Menon.
With each 25-mg vial of Tenecteplase for acute ischemic stroke, the monograph worldwide now includes numerous references to the AcT Trial and pages of data from the stroke team’s research. A little bit of Calgary in every box that will be used to treat stroke patients everywhere.
