Scientists Test New Drug to Control Blood Loss in Trauma Patients

Synthetic estrogen molecule may have a profound effect on the ability to survive major blood loss.

A drug made from estrogen may help control severe bleeding in trauma patients.

The University of Alabama at Birmingham (UAB) is set to launch the first phase 1 human trials for the drug, which may help patients with severe bleeding survive long enough to get appropriate medical care.

A 3-year, $10 million US Department of Defense contract will fund studies of a synthetic estrogen molecule that may have a profound effect on the ability to survive major blood loss.

Irshad H. Chaudry, PhD, professor in the Department of Surgery at UAB and co-principal investigator on the contract performed the initial observations and subsequent research in animal models.

The researchers discovered that following severe bleeding, a single injection increased survival times even in the absence of any fluid resuscitation. Patients experiencing blood loss of approximately 40% or more who do not receive fluid or blood product resuscitation within a few hours usually die.

“The work of Dr. Chaudry and colleagues showed that EE-3-SO4 is extremely effective in improving cardiovascular functions and boosting survival rates following injuries with extreme hemorrhage,” said principal investigator Mansoor Saleh, MD. “This drug could have major implications for treating trauma, from battlefield injuries to life threatening hemorrhage following any injury. We are excited to be launching the first-in-human studies of this drug that was developed by one of our own here at UAB. This is a classic example of bench-to-bedside translational research.”

More than 80% of potentially survivable US battlefield deaths from 2001 to 2011 were due to severe blood loss, according to the Department of Defense. Saleh notes that the drug does not cease a person’s bleeding, but rather helps the body respond to extreme blood loss by mobilizing a variety of physiologic mechanisms.

“Part of our challenges is to identify how EE-3-SO4 works its magic,” Saleh said. “We envision a single dose, injectable medication — administered in the field – which would buy time for a patient to be transported to a medical facility or advanced medical care. The key is to maintain blood flow to the brain and other important organs even while a patient is hemorrhaging.”

The drug works in 3 ways. First, it helps the heart beat more efficiently, enabling it to fully expand and contract while pumping to maximize blood flow.

Next, it lowers blood flow resistance to vital organs, and then gradually elevates blood pressure and promotes sufficient blood flow throughout the body. Finally, it recruits fluid surrounding tissue, increasing blood volume to compensate for blood loss from the wound or injury. The average person has about 10 liters of this interstitial fluid in tissue and about 5 liters of blood.

The DOD contract will allow UAB to begin the first human studies of the medication. The initial studies aim to test the safety and tolerability of the drug in healthy humans who do not exhibit signs of blood loss. Researchers will also use these studies to determine optimal dosing information and study the mechanism of action of this novel agent.

Secondary endpoints include determining the pharmacokinetics of the drug to see if its effect on the heart, blood vessels, and blood volume mimics results seen in non-human studies.

“There are certain relevant clinical and biologic surrogate markers that we look for, as well as predefined cardiac and vascular parameters that should give a good indication of how the drug behaves in humans,” Saleh said.

Subsequent trials will involve administering the drug to healthy patients who have had 1 to 2 units of blood removed in a controlled setting. Researchers will continue to search for physiological responses that indicate whether the drug is having the intended effect on the heart and blood vessels.

Saleh urges patience in those awaiting the treatment, as testing will be a lengthy process with no guarantee that it will prove beneficial for humans. If the drug does meet its endpoints, it could dramatically change how trauma care is delivered.

“A drug such as this would have tremendous utility,” said Jeffrey Kerby, MD, director of the UAB Division of Trauma, Burns and Surgical Critical Care and a former US Air Force trauma surgeon. “Not only is there a need for drugs that could save lives on a battlefield, a drug of this nature would be an important tool in the hands of emergency medical providers responding to traumatic injuries of any kind.”