FDA Approves Abiomed’s RECOVER IV RCT With Exception From Informed Consent

September 16, 2022—Abiomed announced two FDA approvals related to clinical research of the company’s Impella heart pump in acute myocardial infarction (AMI) cardiogenic shock patients.

The FDA has approved the on-label RECOVER IV randomized controlled trial (RCT) for AMI cardiogenic shock patients. The company advised that the study protocol received FDA approval to use the Exception from Informed Consent (EFIC) pathway for enrollment.

Also, the FDA has approved and closed RECOVER III, Impella’s prospective AMI cardiogenic shock postapproval study (PAS).

According to Abiomed, the two-arm RECOVER IV RCT will assess whether percutaneous coronary intervention (PCI) with Impella support initiated before the procedure is superior to PCI without Impella support. Abiomed’s goal in conducting the trial is to achieve a global AMI cardiogenic shock Class I guideline recommendation for Impella and related best practice protocols, including Impella implantation pre-PCI.

As summarized by Abiomed, the primary endpoint of RECOVER IV is all-cause mortality at 30 days. Secondary endpoints include major adverse cardiovascular and cerebrovascular events at 30 days; days alive out of the hospital at 6 months; recovery of left ventricular function; need for durable ventricular assist device or heart transplant; and health-related quality of life as measured by responses to the Kansas City Cardiomyopathy Questionnaire at 1 year.

William O’Neill, MD, who is Medical Director of the Center for Structural Heart Disease at Henry Ford Health in Detroit, Michigan, serves as a RECOVER IV national coprincipal investigator.

Dr. O’Neill commented in Abiomed’s press release, “This landmark trial will be the culmination of over 20 years of research in the interventional therapy of AMI and will apply all the clinical advancements we have made to improve survival and heart recovery for AMI patients with cardiogenic shock as demonstrated in multiple prospective studies.”

Navin K. Kapur, MD, added, “I am optimistic that RECOVER IV will further demonstrate the benefits of hemodynamic support and best practice protocols. These benefits include ventricular unloading using Impella pre-PCI, reduced left ventricular wall stress, reduced pulmonary congestion, increased collateral coronary blood flow, and enhanced cardioprotection so that more AMI cardiogenic shock patients can survive and achieve native heart recovery. The heart team and field have evolved and understand how important myocardial recovery is for both AMI and AMI cardiogenic shock to reduce the growing epidemic of heart failure.” Dr. Kapur is Executive Director of the Cardiovascular Center for Research and Innovation at Tufts Medical Center in Boston, Massachusetts, and a national coprincipal investigator for RECOVER IV.

Regarding the regulatory changes for informed consent in enrollment, the company noted that the FDA created the EFIC pathway in 1996 for emergency clinical research because of the challenges of randomizing patients in AMI cardiogenic shock. These patients require emergent care and are too sick to provide traditional informed consent to enroll in a trial.

The EFIC pathway allows investigators to broadly educate a community about a trial, then enroll patients without consent from patients, their families, or their legally authorized representatives.

In 2022, after engaging with the FDA on the RECOVER IV RCT study design, the company received FDA approval for the RECOVER IV RCT study protocol, which includes the use of EFIC.

Abiomed stated that this community awareness process is rare and only used when the patients being studied are experiencing a life-threatening medical condition causing serious deficiency of mental function. This is a significant milestone for the field and physician leaders. The next steps include local hospital Institutional Review Board approvals and a commitment from physicians to randomize, advised the company.

Gregg W. Stone, MD, who served as study chair for RECOVER IV, remarked in the company’s press release, “This pivotal randomized trial is historic as the first to use EFIC community consent to enroll cardiogenic shock patients. I applaud the FDA for its partnership to help solve the consent challenges in cardiogenic shock RCTs and call on the physician community to enroll and randomize patients in RECOVER IV.” Dr. Stone is professor of medicine and Director of Academic Affairs for the Mount Sinai Heart Health System in New York, New York.

More information on the RECOVER IV RCT study is available on the trial’s website: https://www.heartrecovery.com/recover-iv-rct.

Regarding the RECOVER III PAS, Abiomed stated that the study gathered real-world evidence on AMI cardiogenic shock patients treated with Impella between 2017-2019. The detailed data included stages of cardiogenic shock, cardiac output, and timing of implantation.

RECOVER III fulfills Abiomed’s PAS requirement. The FDA’s approval and closure of RECOVER III further validates Impella as a safe and effective therapy for AMI cardiogenic shock, advised Abiomed.

The company further noted that the Impella mechanical circulatory support device has received the FDA’s highest level of premarket approval and PAS regulatory approval for AMI cardiogenic shock. Based on RECOVER III, Impella’s label for AMI cardiogenic shock will be updated to reflect data for up to 1-year postprocedure.

With the fulfillment of RECOVER III PAS and approval of the RECOVER IV RCT, Abiomed is pursuing an on-label study to strengthen the global guidelines and improve patient outcomes.