Study highlights failure of another experimental stroke drug

Tuesday, December 4th 2001, 12:00 am
By: News On 6

CHICAGO (AP) _ Yet another experimental stroke drug that showed great promise in animals has failed in humans, with the study cut short because patients were dying or showing no improvement.

The study involved aptiganel, or Cerestat, which is part of a once-promising class of experimental drugs known as neuroprotective medicines. Neuroprotective medicines have been a disappointment so far, but the study's author said researchers have not abandoned hope for the drugs.

In the latest study, researchers looked at 628 stroke patients at 156 medical centers in the United States and five other countries.

Three months after treatment, 26.3 percent of those given a high dose of aptiganel had died, compared with 22.5 percent of those who received low doses and 19.2 percent of those who got dummy medication. Patients given aptiganel also had more side effects and showed no improvement compared with the placebo group.

Neuroprotective medicines are designed to block the destructive chemical chain reaction that occurs in the brain hours after an ischemic stroke, the most common type of stroke.

The only approved drug for stroke, TPA, works differently, by dissolving the blood clot that is causing the stroke.

One of TPA's drawbacks is that it must be used within three hours of the onset of stroke. Aptiganel was given in the study within six hours.

The results, published in Wednesday's Journal of the American Medical Association, are not news to stroke researchers already disappointed by a string of failures with other neuroprotective medicines.

The study may signal the demise of hope that neuroprotectors could be used alone to treat strokes, said Dr. James Grotta, director of the University of Texas in Houston's stroke program.

In newer studies, researchers are using neuroprotective drugs earlier, along with TPA, said Dr. Gregory Albers of Stanford Stroke Center, the lead researcher in the JAMA study.

Aptiganel's failure underscores the risks of large-scale, multi-center studies involving potentially harmful new drugs, a JAMA editorial said.

Researchers continued to enroll patients in the study while data showing poor results were being analyzed. Enrollment should have been stopped sooner for safety's sake, Drs. Kyra Becker and David Tirschwell of the University of Washington said in the editorial.

Albers said one of the reasons for publishing the negative results was to highlight some of those same concerns.

``We really need these negative trials to be published to try to figure out what went wrong and to try to do better,'' he said. ``There is a huge unmet need for the treatment of stroke.''

During an ischemic stroke, brain cells deprived of oxygen release large amounts of chemicals that allow calcium to enter and kill nerve cells.

Aptiganel and other neuroprotective drugs aim to inhibit that process. In rat studies, aptiganel reduced brain damage by up to 70 percent when given up to an hour after the onset of a stroke.

Albers' study was funded by Boehringer Ingelheim Pharmaceutical Inc., maker of aptiganel. Other countries involved in the research were Canada, Australia, South Africa, England and Scotland.