The U.S. Food and Drug Administration (FDA) told clinicians Monday, Feb. 4, 2019, that it is evaluating recent interim post-approval study results that suggest a higher mortality rate for patients treated with the Impella RP System (Abiomed, Danvers, Mass.) than the rate previously observed in the premarket clinical studies.
“The FDA wants to ensure you are aware of the mortality rate that has been observed in the ongoing (post-approval study),” the agency wrote in a “Dear Cardiologists” letter.
The letter adds that while the FDA is concerned about the high mortality rate from the post-approval study results, “we believe that when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP system continue to outweigh the risks.”
The FDA approved the Impella RP System on Sept. 20, 2017. The device is implanted centrally via peripheral access to help patients who require temporary emergency support of right ventricular function. Use of the device, which may be up to 14 days, requires patients to stay in the hospital.
In the premarket clinical studies, a total of 44 out of 60 patients (73.3%) survived to 30 days post-device explant or hospital discharge, or to the start of next longer-term therapy, including heart transplant or implantation of a surgical right ventricular assist device.
The FDA mandated that Abiomed conduct a post-approval study as a condition of approval for Impella RP. The study is following 60 newly treated patients for one year through a company registry. The primary endpoint is the same as in the premarket studies. Interim results from the most recent post-approval study report, which reflect device use in a broader patient population, indicate that only 4 out of the 23 enrolled PAS patients (17.4 percent) met the primary survival endpoint, the agency said.
The FDA required additional analyses from Abiomed, and data submitted by the company in January 2019 suggest that the high mortality rate observed in the post-approval study may be primarily related to differences in pre-implant characteristics of the study patients compared to the patients in the premarket clinical studies. Sixteen of the 23 patients enrolled in the post-approval study would not have met the enrollment criteria for the premarket clinical studies, the FDA said.
Specifically, before getting the Impella RP system implanted, patients in the post-approval study were more likely than the premarket clinical study patients to have been in cardiogenic shock for longer than 48 hours, experienced an in-hospital cardiac arrest, been treated with an intra-aortic balloon pump, or suffered a pre-implant hypoxic or ischemic neurologic event, according to the agency.
“It is important to note that the Impella RP (post-approval study) and FDA’s evaluation into this issue are ongoing,” the letter says. “We do not know the root cause for the high mortality rate, and the results are not adjusted for potential confounders.”