FDA Advisory Committee Pushes for Robust Post-Approval Studies for Leadless Pacemakers

While leadless pacemakers could represent a new generation of devices that could improve the comfort and quality of life for some patients, the FDA is concerned about the long-term safety of the devices.

During a Feb. 18 meeting in Gaithersburg, Md., an FDA advisory committee examined some of these concerns, including potential adverse events. The panel ultimately recommended that long-term post-approval studies enroll a large number of patients for leadless pacemakers, which are delivered through a femoral catheter.

Among the adverse events named are perforation and complications through the femoral access, as well as the end of life of the device, once the battery dies. The devices have an estimated longevity of about seven to 12 years, depending on the programmed parameters.

Members of the Circulatory System Devices Panel agreed that studies of 1,741 patients should consider groin complications, perforations, infection, battery longevity and mortality. Due to attrition of the sample size, 500 patients would complete nine years of follow-up and the studies would observe roughly 200 cases of end of life of the device, the panel agreed.

There is limited information on device removal several years post implant. As a result, the panel recommended that the studies also should capture data on how often extraction is attempted, success rates and associated complications.

The panel also agreed that a robust training mechanism is necessary for implanting doctors so they are adequately aware of adverse events and appropriate patient selection methods.

The meeting came as the FDA is preparing to receive premarket approval applications from Medtronic and St. Jude for leadless pacemakers.

Panel Chair Richard Page called the leadless pacemaker a “masterpiece of engineering” and described the technology as “transformative” for patients.

“The purpose of the meeting was to address how to evaluate the devices in a postmarket environment, if or when they are approved by the FDA,” Page tells IDDM. “This was a meeting to describe how to manage the class of devices in the postapproval environment, as opposed to giving an opinion as to safety or efficacy of any single device.”

Race to U.S. Market

Two companies are in the race to the U.S. market with a leadless pacemaker: Medtronic’s Micra Transcatheter Pacing System and St. Jude’s Nanostim Leadless Pacemaker.

Both devices are commercially available in Europe. Medtronic’s Micra received CE Mark on April 14, 2015, based on clinical results from 60 patients implanted with the device over three months. St. Jude’s Nanostim obtained the CE Mark on Aug. 5, 2013, based on clinical results from 33 patients over three months. Late phase clinical trials are ongoing in the U.S. to generate data for premarket approval submissions to the FDA.

In addition, Boston Scientific is developing a leadless pacemaker to complement its subcutaneous-implantable cardioverter defibrillator.

David Steinhaus, Medtronic’s vice president and medical director for the cardiac rhythm and heart failure division, says the company is “committed to ensuring patient safety and device effectiveness over the long-term with ongoing monitoring of the Micra TPS through a thorough post-approval study, a proprietary post-market surveillance program and a rigorous implanter training program.”

Mark Carlson, vice president of global clinical affairs and chief medical officer at St. Jude, says the company appreciates the FDA’s proactive efforts to gain more insight and understanding around leadless pacing technology through “dialogue that will help ensure that leadless technology is adopted with patient safety in mind and with successful clinical outcomes as a top priority.”

Solution to Problems

Leadless pacemakers were among ECRI Institute’s 2016 list of the top 10 technological advances that are poised to affect care delivery over the next 12 to 18 months (IDDM, Jan. 8).

Leadless pacemakers were invented as a solution to some problems associated with leads on conventional pacemakers, says Diane Robertson, ECRI Institute’s director of health technology assessment information services.

“A few years ago, there was a lot of press about the problems with leads in pacemakers. There were big recalls of leads, and there were patient deaths from leads breaking,” she told reporters during a press briefing on Feb. 9 at the institute’s facility in Plymouth Meeting, Pa.

Adding to those concerns was the fact that “to operate on a patient to remove a faulty lead was as risky as leaving the lead in,” she added. — Jonathon Shacat