Ongoing trial assessing novel assay to determine response to cardiac regenerative therapy

Carl J. Pepine

The CardiAMP-HF trial will assess a novel cell potency assay to select patients with ischemic cardiomyopathy who may be the best responders to cardiac regenerative therapy, according to a paper published in Circulation Research.

“We designed a trial that brings personalized medicine to the regenerative medicine space in cardiovascular disease,” Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, professor in the division of cardiovascular medicine at University of Florida, Gainesville, said in an interview. “To the best of our knowledge, that has not been done before. Simply put, we have in prior studies identified certain characteristics of patient’s bone marrow cells and circulating progenitor cells that are associated with a beneficial response to cell-based therapy.”

Patient enrollment

Multiple centers around the U.S. will enroll 260 patients with ischemic cardiomyopathy and left ventricular ejection fraction between 20% and 40% over the next year. These centers include one led by Peter V. Johnston, MD, medical director of the cardiac catheterization laboratory at Howard County General Hospital and assistant professor at Johns Hopkins University School of Medicine.

“We and most of the people in the world who address this have chosen to attack the heart failure problem and heart failure with reduced ejection fraction mainly because these patients consume tremendous resources, they have repeated hospitalizations and they die early,” Pepine told Cardiology Today.

Patients will undergo screening with a mini-bone marrow aspiration (5 cc) that is sent to a core lab at Baylor University to measure properties and surface marker expression in a proprietary assay (BioCardia) developed to identify therapeutically potent bone marrow cells.

“Based on [bone marrow] characteristics, a ‘potency score’ has been created,” Pepine told Cardiology Today. “If the patient has a high enough potency score based on those characteristics, we then enroll them into the trial. They return to have a 60 cc bone marrow sample, their cells processed on-site (approximately 30 minutes) and then the cell preparation is injected into their heart muscle. The concept is a personalized approach based upon the individual patient’s bone marrow, progenitor cell characteristics. It’s our belief that this will yield a more robust response than has been observed in prior trials.”

Those who meet the potency assay requirement will be randomly assigned on a 3:2 basis to receive either transendocardial autologous bone marrow mononuclear cells or a sham procedure.

The primary outcome is change in 6-minute walk distance adjusted for major adverse CV events at 12 months.

“Roll-in cohort” results

Ten patients have been enrolled in the open-label roll-in cohort from three centers (University of Florida, University of Wisconsin and Johns Hopkins University). At 6 months, there were improvements in 6-minute walk distance (47.8 m; 20.5% relative improvement; P = .01) and NYHA class (P = .037). There was also a beneficial trend in Minnesota Living with Heart Failure Questionnaire score (–10.2; 31% relative improvement; P = .21).

The randomized phase of the study is currently enrolling patients and aims to enroll 260 patients from multiple sites across the U.S., according to Pepine, who is the co-primary investigator for the project.

Pepine said another patient population with HF with preserved ejection fraction may be another target for the cell potency score.

“As we speak, there’s no recommended treatment for this HFpEF group of patients,” Pepine told Cardiology Today. “We believe that the fundamental problem is an inability for the main pumping chambers of the heart to relax appropriately and fill appropriately. In other words, the pump doesn’t fill well. We believe that certain types of stem cells can change that.” – by Darlene Dobkowski

References:

Johnston PV, et al. Circ Res. 2018;doi:10.1161/CIRCRESAHA.118.313425.

Raval AN, et al. Am Heart J. 2018;doi:10.1016/j.ahj.2018.03.016.

For more information:

Carl J. Pepine, MD, MACC, can be reached at the Cardiology Today office, 6900 Grove Road, Thorofare, NJ 08086.

Disclosures: The CardiAMP-HF trial is funded by BioCardia and the Maryland Stem Cell Research Fund. Pepine and Johnston report they are members of the executive steering committee for CardiAMP-HF and receive consultant fees and/or grant support. Please see the study for all other authors’ relevant financial disclosures.