Death halts "abortion pill" trial: fatality may be used to block drug's approval in Canada

Abstract

In its statement, the Population Council noted the combination of mifepristone and misoprostol has been used to perform more than 500,000 medical abortions in Europe, has been widely studied, and has been available for a year in the U.S.--yet there has been no previous occurrence of this type.

TORONTO - A multicentre Canadian clinical trial of mifepristone, or "the abortion pill," has been suspended following the death of a study participant.

The New York-based Population Council, which sponsored the study, released a statement Sept. 10 that announced the fatality and said enrolment for the trial would be stopped while the death was investigated.

The Population Council said initial reports suggested the death was caused by septic shock relating to a rare clostridium infection.

"We really believe the death was not caused by the drug," council spokeswoman Christina Horzepa told the Medical Post. "However, we have suspended enrolment in the trial while we investigate."

After years of false starts, the controversial drug, also known as RU-486, was approved for use in medical abortions by the U.S. Food and Drug Administration (FDA) last fall. It is not yet approved in Canada.

Health Canada spokeswoman Roslyn Tremblay said the agency was investigating the circumstances of the woman's death. "This will be done as expediently as possible," said Tremblay.

The FDA also has launched an investigation, which they said could take weeks to complete.

"The FDA is looking into all aspects of the situation. It is premature to speculate on what caused the woman's death, as much more information is needed before any conclusion is drawn. It may be weeks before definitive information is available," said an FDA spokeswoman.

Meanwhile, the death has caused no change in the status or availability of mifepristone in the U.S., according to the FDA.

The death is being subjected to unusual scrutiny because although the research is taking place in Canada, the study's sponsor, and the drug's manufacturer and distributor (Danco Laboratories) are based in the U.S.

Mifepristone is used in concert with misoprostol (Cytotec) to provide abortions early in pregnancy. It was being studied at centres in Vancouver, Toronto, Quebec City and Sherbrooke, Que. The Population Council would not say at which of the Canadian sites the death occurred.

The trial's principal investigator, Dr. Ellen Wiebe, said the patient received a dose of mifepristone Aug. 23, followed by misoprostol two days later.

When the patient returned to the clinic for followup on Aug. 28, an ultrasound showed the abortion was complete. The patient then developed signs of infection, and went into hospital on Aug. 29. She deteriorated rapidly, and died Sept. 1. The trial was suspended five days later.

"I did a careful investigation myself, and I am convinced the drugs had nothing to do with the death," said Dr. Wiebe, in an interview from Vancouver. She said the woman's autopsy results indicated the death was caused by Clostridium sordellii.

Dr. Wiebe acknowledged the death would probably be used as a political tool to block approval of the drug in Canada. "The anti-choice people use what they use," she said. "Basically, we are very confident the drug is safe."

The purpose of the trial was to compare three different doses of misoprostol to determine which is most effective in combination with mifepristone. The study had been under way since February, and researchers had already recruited 900 women toward an expected sample size of 1,500.

The location of the fatality is not being released to keep private the fact that the woman had an abortion.

The first study by Dr. Wiebe and the Canadian team has already been completed, and is in the hands of a publisher. It compared the efficacy of the cancer and arthritis drug methotrexate--which is used off label as an abortifacient--and mifepristone.

"And yes, mifepristone is better than methotrexate," said Dr. Wiebe, a clinical professor of family medicine at the University of British Columbia.

Mifepristone, a synthetic steroid, works early in the pregnancy by blocking progesterone and making it difficult for a fertilized egg to attach to the lining of the uterus. It is used in combination with the prostaglandin misoprostol, which triggers uterine contractions.

Dr. Wiebe said she still hopes mifepristone will be approved here. "Canadian women certainly have the right to the best drug available--and this is it, so we just have to keep going."

In its statement, the Population Council noted the combination of mifepristone and misoprostol has been used to perform more than 500,000 medical abortions in Europe, has been widely studied, and has been available for a year in the U.S.--yet there has been no previous occurrence of this type.