May 22, 2007

Secret Test Gave Patients a Substitute for Blood: In Detroit, One of 9 Died; U.S. Agency is Investigating

By Steve Neavling, Detroit Free Press

May 22--You're in a car crash, unconscious and bleeding profusely.

Without your consent, you are injected with an experimental blood substitute being randomly tested on victims of car crashes, shootings and other trauma. That's exactly what happened to nine trauma patients -- one of whom died -- at two Detroit hospitals last year.

Nine other patients randomly selected to receive the standard treatment -- saline solution and real blood -- survived.

The blood substitute, Polyheme, was tested in 20 cities.

The U.S. Food and Drug Administration is investigating 46 deaths nationwide among the 349 subjects who received Polyheme in the clinical trial. By contrast, 35 of the 363 patients given the standard treatment died.

In most clinical studies, patients must volunteer, usually doing so with the hope of being cured through the experimental treatment.

But the Polyheme trial was one of 15 no-consent studies permitted by the FDA since 1996, when it began allowing researchers to enroll patients in clinical tests without their permission if the treatment showed enough potential to save lives.

Some medical ethicists are outraged at the Polyheme trial.

"This is completely unethical," said Dr. Sidney Wolfe, director of Public Citizen's Health Research Group. "They withheld blood -- the gold standard -- for a product that has proven in previous clinical circumstances to raise the death rate."

Inside the study

Northfield Laboratories of Evanston, Ill., Polyheme's manufacturer, contends there was no other way to test the product. Trauma patients are generally unconscious and cannot give consent.

"If I were injured, would I want Polyheme? Absolutely. I would prefer it," said Dr. Larry Diebel, who led the trials in Detroit and is a medical professor at Wayne State University. Detroit Receiving and Sinai Grace hospitals participated in the testing.Northfield maintains that there were violations of study protocols with nearly one-fifth of the participants. In some cases, it said, paramedics gave Polyheme to people who were going to die regardless of treatment.

The company plans to release a report as early as this month from a research organization it contracted with to review the data. In December, Northfield's data showed that if 122 questionable cases were excluded, the increase in the mortality rate for those who received Polyheme over those who received blood was just 18.7%. Without those cases being excluded, the rate was 49%.

To fill a critical need

Another no-consent study involving Hemopure, a similar blood substitute manufactured by Biopure of Cambridge, Mass., was halted in December by the FDA.. The agency raised concerns that the Navy personnel on whom the product was being tested were dying and suffering heart attacks.

The FDA declined to comment on the Polyheme study while it is reviewing it.

Advocates say Polyheme, which is made by extracting oxygen-carrying hemoglobin from human red blood cells, comes along at a time when the United States is facing a critical blood shortage.

Nationally, about 100,000 people die of bleeding injuries every year. Medical professionals say some deaths could be prevented if not for blood shortages.

The shortage of O-negative blood, the universal-donor blood type that can be administered to any patient, is especially acute. At southeastern Michigan hospitals, the demand for O-negative is so high that none is stockpiled, said Martha Kurz, spokeswoman for the American Red Cross of Southeastern Michigan.

A blood substitute such as Polyheme could be especially useful in combat because the product has a long shelf life and doesn't need to be refrigerated, researchers say.

Hemorrhaging remains a main cause of death on the battlefield, and the U.S. Army reports about 60% of those injured in Iraq suffered substantial blood loss.

Earlier problems

Northfield Laboratories was criticized in 2001 for a four-year Polyheme study on aneurysm-surgery patients.

Ten of 81 patients who were given the substitute suffered heart attacks, including two who died. None of the 71 patients on standard therapy had heart attacks.

The company blamed the heart attacks on an excess of total fluids given to Polyheme patients and halted the study.

The second trial was approved by the FDA, in part, because Northfield was testing Polyheme for a different purpose.

The Detroit Medical Center, which runs the two Detroit hospitals that participated in the second trial, said the lone fatality involved a man hit by an SUV. The DMC declined to comment further on the trial or give the names of the patients, citing privacy laws.

Diebel, the trials' leader in Detroit, said all of the Detroit hospitals' patients were victims of shootings or car crashes and were between the ages of 19 and 55.

He said he believes Polyheme is a breakthrough in emergency medicine. In addition to being compatible with all blood types and storing longer than blood, it is virtually free of viral transmission.

Northfield Laboratories saw its stock plummet 75% after the December disclosure of the death rate, prompting a class action by investors who claim they were never told about the number of heart attacks in the first study.

Contact STEVE NEAVLING at 586-469-4935 or [email protected]

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