As the recipient of a $1 million grant from the DoD’s Medical Technology Enterprise Consortium (MTEC), tissue-engineering firm Humacyte, Inc. selected the Coalition for National Trauma Research (CNTR) to manage its multi-site study of vascular trauma using the PROOVIT (PROspective Observational Vascular Injury Treatment) registry. Seeking FDA approval for use of its Human Acellular Vessel (HAV) in traumatic vascular injury, Humacyte’s partnership with CNTR draws on the coalition’s experience managing multicenter studies and previous involvement in PROOVIT.
The PROOVIT registry, a multicenter study sponsored by the American Association for the Surgery of Trauma, contains datapoints from more than 4,000 vascular trauma patients. This registry is the ideal real-world datasource from which to extract and evaluate outcomes related to vascular graft patency at least six-months after reconstruction. With management and oversight by CNTR, investigators will review the medical records of patients who suffered life- or limb-threatening vascular trauma requiring surgical repair and evaluate for evidence of infection, thrombosis, re-intervention, or limb loss. The study, thus, will assess the utility of PROOVIT as a means to compare two approaches to traumatic vascular injury repair—arterial reconstruction with autologous vein and, conversely, with Humacyte’s Human Acellular Vessel (HAV).
In addition to supporting Humacyte’s bid for FDA approval, a byproduct of the effort will be an expansion of PROOVIT registry data elements and data validation, as any gaps that exist will be filled when investigators reach out to recovered patients to learn about their outcomes.
Jeffrey H. Lawson, MD, PhD, CEO, and Vascular Surgeon commented on how approval of a product like the HAV would change the practice of medicine. “In clinical practice, having an immediately available, off-the-shelf vascular conduit that is resistant to infection and durable would be a remarkable addition to vascular surgery,” he said. “Having these types of biotherapies readily available could make many of our vascular repair procedures easier, safer and better for the patients we care for.” As trauma is nearly impossible to study following traditional clinical study designs, Dr. Lawson added, “The collaboration between MTEC, CNTR, and the DOD brings together the ideal team to leverage FDA’s increasing acceptance of RWE study designs to support regulatory decision making.”
“Vascular injuries are a significant contributor to loss of life and limb following acute trauma in both military and civilian scenarios, and amputation rates following traumatic injury are reported to be as high as eight percent,” explained Todd Costantini, MD, the primary investigator on the project. “So, there’s an urgent need for novel vascular repair options to achieve improved clinical outcomes and enhance quality of life for patients.”
While the current standard of care for vascular injuries requiring open repair is the use of autologous vein grafts, several scenarios can preclude this intervention, including concomitant injury to the vein, insufficiency of vein present, or absence of vein due to previous medical procedures. In instances when vein is available, the process of harvesting can demand increased time and resources and can negatively influence clinical outcomes. When autologous vein is not available, synthetic graft materials (including ePTFE and Dacron) are typically used. However, synthetic materials are known to have inferior clinical outcomes and are prone to infection, leading to contraindication for use in potentially contaminated fields. As such, the optimal vascular conduit would provide clinical outcomes similar to autologous vein, without requiring vein harvest and being readily available like synthetic products.
Joseph Dubose, MD, co-PI on the project, said, “In prior and ongoing preclinical and clinical studies, the HAV has been shown to integrate with host physiology and exhibit resistance to infection compared to synthetic alternatives, and it is currently being investigated in a Phase II/III study for trauma.” In light of the significant potential for this product, the U.S. Department of Defense has supported development of the HAV, designating it a Priority Product.
Humacyte is currently looking to expand to up to 30 clinical sites, many of which also contribute to PROOVIT, including The University of Texas Health Science Center Houston, LAC/University of Southern California, University of Florida Health Jacksonville, Loma Linda University of Medical Center, University of Tennessee Memphis, University of Maryland – Shock Trauma Center, Emory University, and University of California San Diego.
This effort is sponsored by the Government under Other Transactions Number W81XWH-15-9-0001.
Humacyte, Inc. is a privately held regenerative medicine company based in Durham, North Carolina that develops engineered human blood vessels known as HAVs (human acellular vessels). These HAVs, if approved, would benefit people with traumatic vascular injuries, End-Stage Renal Disease (ESRD), peripheral arterial disease (PAD), and in the future could potentially help patients needing vascular reconstruction and Coronary Artery Bypass Grafting (CABG). Humacyte was co-founded in 2004 by Laura Niklason, M.D., Ph.D., a world leader in cellular therapies/regenerative medicine and Nicholas Greene Professor of anesthesiology and biomedical engineering at Yale University; Dr. Shannon Dahl; and molecular biologist Dr. Juliana Blum. Visit humacyte.com for more information.
MTEC is a biomedical technology consortium led by the U.S. Army Medical Research and Development Command (USAMRDC) with members from industry, academia and the nonprofit sector. MTEC aims to accelerate the development of medical solutions that prevent and treat injuries affecting America’s military members and veterans. Learn more about MTEC.
A member of MTEC, the Coalition for National Trauma Research works to enhance trauma research by advocating for sustainable research funding commensurate with the burden of disease, coordinating research efforts across professional organizations spanning the continuum of injury care, and strengthening the infrastructure for multicenter investigation. Find CNTR online at NatTrauma.org and on Twitter at @NatTrauma.