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Blood Substitutes Linked to Deaths

Patients treated with experimental blood substitutes were
30% more likely to die and more than twice as likely to have heart attacks as
patients who did not get the blood substitute products, a pooled analysis of
the research reveals.

Combined results from 13 published and three unpublished industry-sponsored
trials showed the increase in risk for all the hemoglobin-based blood
substitute products tested and for all populations studied, including trauma
patients and those having heart, vascular, or elective surgery.

The study, conducted by researchers from the National Institutes of Health
(NIH) and the consumer advocacy group Public Citizen, is scheduled for
publication in the May 21 issue of The Journal of the American Medical
Association
.

But the findings were made public online Monday, the day before a planned
two-day FDA-sponsored workshop examining the safety of the blood
substitutes.

NIH researcher Charles Natanson, MD, says the analysis makes it clear that
the products are too dangerous for use in human clinical trials.

One of the blood substitutes, Biopure Corp.'s Hemopure, is approved for use
in humans in South Africa. None is approved for human use in the U.S., but
there are five ongoing clinical trials involving the blood substitutes,
Natanson says.

"I don't believe this research should go forward in humans until these
products have been reformulated and animal studies show them to be less
toxic," he tells WebMD.

The Hope for Blood Substitutes

Blood substitutes that need no refrigeration, have a long shelf life, and
don't require blood type matching hold the promise of saving lives in remote
and battlefield settings and easing blood shortages everywhere.

Fears of a tainted blood supply in the early days of the HIV pandemic created great
interest in developing safe and effective blood substitutes. Much of that
research has involved the protein hemoglobin, which gives red blood cells their
ability to carry oxygen.

In the newly published analysis, Natanson and colleagues examined data from
industry-sponsored studies of five hemoglobin-based products involving 3,711
patients.

"It makes sense to examine these products as a class because they all
bind oxygen and have a common mechanism of toxicity," he says. "When we
did this we found the risk of death and (heart
attack ) to be consistent across the products."

But in a statement released Monday, a spokesman for Biopure calls the
analysis "significantly flawed."

"There are vast differences among these products that make any pooling
of data flawed, especially across different clinical experiences,"
Biopure's Vice President of Medical Affairs A. Gerson Greenburg, MD, PhD, says
in the statement.

FDA Failed, Researchers Say

Natanson and colleagues criticized the FDA for failing to do its own
analysis of safety data from the clinical trials years ago.

They write that such an analysis would have demonstrated significant risks
associated with the products as early as 2000.

"Had the agency placed a moratorium on trials at that point,
product-related deaths and [heart attacks] in subsequent trials most likely
would have been prevented," they write. "Such data were not available
to scientists, the public, institutional review boards, or competing [blood
substitute] manufacturers."

Ottawa Health Research Institute senior scientist Dan Fergusson, PhD, agrees
that more timely dissemination of the safety data probably would have saved
lives.

Fergusson co-wrote an editorial accompanying the newly published
analysis.

"A lot of the safety data was not made public, and it matters," he
tells WebMD. "If I am someone designing and enrolling patients for the next
trial, I need that information."

Fergusson says a registry of blood substitute trials is badly needed to
address the issue of safety, along with regulaory changes to require prompt
reporting of both negative and positive study findings.

In his editorial, he called for a critical and systematic review of all the
hemoglobin-based blood substitute research before further human trials are
considered.

But he tells WebMD that the blood substitute research should not be
abandoned.

"A lot of good has come out of this research," he says. "We have
a better understanding of the basic physiology of how oxygen is delivered to
the tissues. But I think it is fair to say that many of the companies that did
this research were not forthcoming with their safety data."

By Salynn Boyles
Reviewed by Louise Chang
©2005-2008 WebMD, LLC. All rights reserved

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