New
Service for TodaysSeniorsNetwork.com
readers...roll mouse over, click on
highlighted links in stories to review items
from Amazon
Now, keep up to date
with daily feeds of newly posted stories
about America's Seniors...click on the box
to the left
Use of blood
substitutes linked to increased risk of
death, heart attack
Newswise — An analysis of studies involving the use of
hemoglobin-based blood substitutes indicates
their use is associated with an increased
risk of death and heart attack, according to
a JAMA study being released early
online, and will appear in print in the May
21 issue of JAMA.
The development of a blood substitute—a liquid that has a
long shelf-life, does not need refrigeration
and does not cause infection—would provide a
potentially lifesaving option for surgical
and trauma patients with shock from loss of
blood, especially in rural areas and
military settings.
“To date, a large proportion of blood substitutes in
development have been hemoglobin-based
products [hemoglobin is the oxygen-carrying
protein in the red blood cells].
"Yet randomized controlled trials completed as early as 1996
have raised questions about the safety of
these products and have failed to
demonstrate clinical benefit. Nonetheless,
at least 1 of these products is approved for
use outside the United States and new
clinical trials are being conducted or
planned worldwide,” the authors write.
Charles Natanson, M.D., of the National Institutes of Health,
Bethesda, Md., and colleagues conducted an
analysis of previous studies to examine the
association between hemoglobin-based blood
substitutes (HBBSs) and the risk of heart
attack and death in trials using these
products in surgical, trauma and stroke
patients.
The authors searched databases and other sources for
randomized controlled trials that included
patients age 19 years and older who received
HBBSs therapeutically. Sixteen trials that
met the authors’ criteria were identified,
involving five different products and 3,711
patients.
There were a total of 164 deaths among HBBS-treated patients
and 123 deaths among patients in the control
groups.
Overall, the HBBS products were associated with a 30 percent
increased risk of death.
There were a total of 59 heart attacks among HBBS-treated
patients and 16 heart attacks among patients
in the control groups. For these studies
combined, there was a 2.7 times increased
risk of heart attack among patients
receiving HBBSs.
Subgroup analysis of these trials indicated the increased
risk was not restricted to a particular HBBS
or clinical indication.
“The pattern of increased risk demonstrated by a variety of
HBBSs across an array of clinical settings
argues for a policy whereby any new or
existing HBBSs should be subjected to
pre-clinical studies in animal models that
replicate the known toxicities of HBBSs
demonstrated in humans before further
clinical trials of this class of product are
allowed to proceed,” the authors write.
The researchers also discussed the regulatory process that
permitted repeated trials with these agents
despite persistent safety concerns.
“Sponsors are required by law to report their results to the
Food and Drug Administration (FDA) in a
timely fashion after studies are completed,
even if they do not publish their findings.
''However, the data reported by sponsors to the FDA are not
made public by the FDA unless the product is
approved or an advisory committee is
convened to discuss the product. The
cumulative mortality analysis … indicates
that prompt meta-analyses of the HBBS trials
by the FDA most likely would have
demonstrated significant risks by 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.
"However, such data were not available to
scientists, the public, institutional review
boards, or competing HBBS manufacturers,”
the authors write.
Five trials of HBBSs reportedly are ongoing in eight
different countries outside the United
States and at least one trial is being
planned for the U.S.
“The results of all trials of experimental agents conducted
in human beings—from phase 1 to phase
4—should be fully and expeditiously
disclosed to the scientific and medical
communities. The case study detailed here
underscores both the scientific inefficiency
and the real risks to patients of the
current failure to report data promptly.”
Editorial: The Future of Clinical Trials Evaluating Blood
Substitutes
In an accompanying editorial, Dean A. Fergusson, M.H.A.,
Ph.D., and Lauralyn McIntyre, M.D., M.Sc.,
of the Ottawa Health Research Institute and
the University of Ottawa Faculty of
Medicine, Ottawa, Canada, write that the
timely reporting of all evidence independent
of positive or negative findings is not only
essential but ethical.
“Natanson et al provide evidence that study results were made
public well after the trials had stopped
enrollment. Thus, it was not possible for
ethics boards to properly review proposed
studies because they did not have all
available information.
"Additionally, patients or proxy decision makers were not in a
position to make well-informed decisions at
the time of providing informed consent.
Regardless of whether studies are conducted
under the auspices of commercial or academic
entities, studies need to be centrally
registered and their findings duly reported.
Not doing so places patients at unnecessary
risk.”
“Based on the findings of Natanson et al and the consistency
of these results with pre-clinical evidence
of potential toxicity, further phase 3
trials of hemoglobin-based oxygen carriers (HBOCs)
should not be conducted. There has been a
tremendous amount of resources expended and
knowledge gained from the pursuit of HBOCs.
This vast body of knowledge should be
reviewed critically and systematically,
including theoretical constructs, animal
studies, mechanistic studies, and
early-phase clinical trials before further
phase 3 trials are undertaken,” they write.
“Until the mechanisms and potential
toxicities of HBOC products are better
understood, patients cannot be placed at
unacceptable risk.”
...
...
...