A new study promises to provide much more accurate data concerning complication rates for replacements and system upgrades of implantable pacemakers and defibrillators.

Biotronik (Lake Oswego, Oregon/Berlin) in late July reported that it has enrolled the first patient in the landmark REPLACE Registry, which it dubbed the “first and largest prospective trial” focusing on the complications associated with these types of devices independent of the manufacturer.

The first U.S generator change procedure performed under this protocol was done at Caritas St. Elizabeth Medical Center (Boston) by principal investigator Charles Haffajee, MD. Haffajee replaced a dual-chamber ICD that had reached its Elective Replacement Indication (ERI).

Haffajee indicated that this registry is long overdue and said that “the actual complication rates, the type of complications, some of which are life-threatening, are often unreported and have never been collected in a prospective fashion in an unbiased registry.”

According to Biotronik, primary sponsor of the effort, the 1,750-patient registry will utilize only devices approved by the FDA and will include all device models, whatever the manufacturer. This obviously could provide some interesting, perhaps eye-opening results for the various companies when the registry reaches completion in 18 months.

According to Kevin Mitchell, VP of clinical studies for Biotronik, impetus for the registry came from numerous product recalls that the industry has experienced over the last two years. And he also cited the rather significant disparity between a Canadian study that revealed a complication rate of 8.1% associated with replacement of these systems and the experience of a retrospective analysis by Mayo Clinic (Rochester, Minnesota) reporting a 2% complication rate.

Mitchell — who developed the idea to start the study — told CDU, “We did a literature search to see if there had been any prospective studies on device complications with generator changes, and there weren’t any, so we saw this as an opportunity to present something back to the medical community from a scientific point of view that they’re very interested in.”

Jeanne Poole, MD, director of electrophysiology at the University of Washington Medical Center (Seattle) and national principal investigator for the REPLACE Registry, called the study “a very important prospective study for physicians who implant these devices. It is well designed to collect important data currently lacking on risks associated with device generator replacements. With the growing volume of defibrillators implanted for primary prevention purposes the study will provide a better understanding of the risks that can be anticipated for elective generator replacements or system upgrades.”

In an industry with a growing number of device implants specifically for primary prevention applications, as noted by Poole, coupled with sporadic device advisories notifying clinicians of the potential for adverse device performance, there is a critical need to characterize complication rates. A key benefit is expected to be in aiding electrophysiologists and cardiologists in making decisions concerning the risk/benefit equation of elective replacement surgeries.

The registry will be conducted in 75 to 100 centers across the U.S. and will be monitored independently by a Clinical Events Committee chaired by Marye Gleva, MD, an electrophysiologist at Washington University School of Medicine (St. Louis). Several key co-morbidity variables will be evaluated to further reveal the relative risks inherent in these.

Mitchell said that there are two groups of patients being enrolled in this study.

The first is made up of those requiring “straightforward” device changes in which a generator is replaced when a battery in a unit becomes depleted.

The second group, he said, includes patients that have an existing generator but “need to be upgraded” to a different type of device because their condition has worsened. This group usually requires lead replacement in edition to generator changes, so these are more complex cases, Mitchell said.

Mitchell said the expected average complication rate for the generator-only replacement group, which will enroll 1,000 patients, is 1.5%. For the upgrade replacement group, enrolling the remaining 750 patients, the average complication rate is projected to be about 5%

The company said that the registry was designed by a steering committee composed of both academic and private practice electrophysiologists to capture the information of greatest benefit to implanting physicians. The database, study statistician, clinical research organization, and clinical events committee are all operationally independent of Biotronik, Biotronik said.

In other company-related news, Biotronik said that it has enrolled the 1,000th patient in the TRUST (Lumos-T Safely RedUceS RouTine Office Device Follow Up) study. This enrollment, performed at the Cleveland Clinic (Cleveland), completes the initial target enrollment of 1,000 patients three months ahead of projected study completion timeframe, the company said.

TRUST is a randomized, prospective, multi-center trial designed by a steering committee comprised of eight electrophysiologists and sponsored by Biotronik. It is evaluating whether outcomes in patients with Lumos and Lumax VR-T/DR-T defibrillators followed by Home Monitoring technology and IEGM Online are at least equivalent if not better than with those followed by the current standard of care of in-person follow-up.

Secondary endpoints include the assessment of Home Monitoring and IEGM Online for early notification of asymptomatic events and to triage patient-initiated device inquiries.

Recently, the study was amended to formally evaluate the trial’s pre-specified secondary endpoint. The focus of this amendment will be on the assessment of early detection of cardiac events such as VT, VF and AF.

To obtain appropriate statistical power, the enrollment level has been increased to 1,515 patients. However, the evaluation of the primary endpoint will still occur when the 1,000th patient has completed the study follow-up period, the company said.

The Home Monitoring and IEGM Online system is designed to provide notification of critical alterations of the heart rhythm, as well as any potential technical malfunction of the device. Additionally, the company’s Lumos and Lumax ICDs are the sole devices of their kind worldwide that can include an IEGM (cardiac electrogram) immediately and automatically with a cardiac event notification, the company says.