Results of Blood Substitute Study

Lehigh Valley Health Network (LVHN) reported results of a trauma research study with the blood substitute PolyHeme. The study was conducted under a federal regulation that allows research in certain emergent, life-threatening situations using an exception from the requirement for informed consent. This trial enrolled patients who were at risk of dying from severe trauma and blood loss, and was conducted at 32 Level I trauma centers in 19 states, including Lehigh Valley Hospital-Cedar Crest (LVH).

Before the study began , LVHN completed a process of community notification and consultation in connection with this study, as is mandated by federal regulation. Now that the study has been completed and the results have been analyzed and presented to the American College of Surgeons, LVHN is providing the results of the study to the community as is required by the regulation.

Study Design

In this clinical study, adult patients meeting the eligibility criteria were randomly assigned to initially receive infusions of either PolyHeme or the current standard of care ("Control") in order to compare survival. Patients who sustained severe injuries and blood loss were enrolled at the scene of injury. Patients who were pregnant, who had serious head injuries, required CPR, or who had a known objection to blood transfusion were not included in the study.

Treatment began before arrival at the hospital, either at the scene of the injury or in the ambulance, and continued in the early post-injury period in the hospital. Patients in the PolyHeme group received PolyHeme as their first fluid, to a maximum dose of up to 6 units of PolyHeme or 12 hours after injury. Patients who continued to bleed received donated blood thereafter. Patients in the Control group received IV salt water at the scene and during transport and were given donated blood transfusions as needed upon arrival at the hospital.

Study Results

There were 714 total trauma patients treated in this study, at all the study sites. Eighty-two patients died, 46 (13%) of the 349 patients who received PolyHeme and 36 (10%) of the 365 patients who received Control. At LVHN, 24 patients were enrolled in the study; nine patients received PolyHeme and 15 received Control. One patient died in the PolyHeme group and the cause of death was blunt chest trauma. This death was not related to the PolyHeme transfusion. There were no deaths in the Control group at LVHN.

Nationally, the difference in deaths between the groups fell outside the boundary to meet the primary efficacy endpoint agreed upon with FDA. However, the difference in the number of deaths was not statistically significant, meaning the outcomes were similar, regardless of the treatment the patient received. Of the 714 patients in the study, 124 had “protocol violations.” Some patients should not have been enrolled, and some did not receive the assigned treatment. Of the 590 patients where the protocol was correctly followed, 60 patients died, 31 in the PolyHeme group (11%) and 29 (9%) in the control group. At LVH, each protocol violation was investigated and it was determined that no patient had any adverse outcome or safety issue related to the violations.

The physician-investigators reported any complications they observed. As is expected in any study of severely injured and bleeding patients, most of the patients in this study had “adverse events (AEs).” FDA defines what constitutes an adverse event to include any physical or laboratory abnormality that happens to a patient in a clinical trial. An AE is not necessarily caused by the test product; control patients also have them. In the PolyHeme group, 324 of 349 (93%) patients had AEs, as did 322 of 365 (88%) Control patients. The most common adverse events reported in this study in both groups of patients were: anemia (35% PolyHeme, 32% Control); low calcium/potassium (32% PolyHeme, 34% Control); and fever (29% and 27% respectively).

The FDA defines “Serious Adverse Event” (SAE) to include any AE that results in death, is life-threatening, keeps the patient in the hospital longer, or causes lasting disability. An SAE is not necessarily caused by the test product; control patients also have them. The most common serious adverse events reported in this study were: pneumonia (8% PolyHeme, 6% Control); multiple organ failure (7%, 6%); and respiratory failure (6%, 5%). In addition, a greater number of heart attacks were reported by the investigators in the PolyHeme group (11) than in the Control (3). None of the heart attacks was considered “possibly” or “probably” related to the study treatment. One patient in each group required intervention (cardiac catheterization). The combined incidence of other cardiovascular events reported in the patients in this study was: heart failure events (5% PolyHeme, 5% Control); serious rhythm disturbances (4% PolyHeme, 2% Control) and stroke syndromes (1% PolyHeme, 1% Control). All AEs and SAEs which occurred at LVH were unrelated to Polyheme or study procedures.

PolyHeme was studied for use in bleeding patients without early access to blood, not for use in place of blood when blood is available. This study was conducted in largely urban areas, where transit times were short. There are many aspects to the evaluation of a potential new therapy before approving it for general use, including what the benefit-to-risk profile of the product is. The patients who would qualify to be given the blood substitute would be at risk of dying from blood loss. Without blood, the risk of dying is even greater. At this time, there is no adequate alternative to blood that can be given to bleeding patients when blood is not available. Based on the results of this study as well as earlier published results, PolyHeme may provide a survival benefit to bleeding patients who do not have access to blood.

About Trauma

According to the Centers for Disease Control, trauma is the leading cause of death in Americans under the age of 45, claiming more than 140,000 lives and permanently disabling 80,000 people each year. Forty seven million Americans live more than an hour away from a trauma center, and only one in four lives in an area served by a coordinated trauma care system. Sixty percent of trauma deaths occur in rural settings, even though those areas account for only 20% of the U.S. population.

* For any questions regarding this information or if you are interested in additional information, please contact Michael Pasquale, M.D., at (610) 402-1350.

This page last updated 1/28/10 11:13 AM