RECOVER IV Trial of Impella Heart Pump Halted

An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor Abiomed, Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.

Abiomed, Inc., which manufactures the Impella microaxial flow pump, said in a statement that the trial’s Data and Safety Monitoring Board recommended stopping RECOVER IV.

“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”

The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.

DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.

Loss of Clinical Equipoise

“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,'” said Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.

Kapur and O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.

Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said O’Neill. But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”

Getting Hearts Pumping

The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.

“Impella is the only heart pump that can be introduced percutaneously through the leg,” said O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.

DanGer Shock: A Leap Forward

Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.

“The DanGer trial is a huge advance,” said O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” O’Neill said this is one of the best outcomes he has seen during his long career.

Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.

“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.

“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”

New Cardiogenic Shock Trials

O’Neill and Kapur said the groundwork they laid for RECOVER IV can be used for new trials.

“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said O’Neill. The researchers are poised to begin new trials once protocols are developed.

What will the next trials investigate?

DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said O’Neill, and these could be tested in trials.

Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.

Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.

“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”