Medtronic Kicks Off the New Year With Major Clinical Studies

U.S. Enrollment in Drug-Eluting Balloon Trial Completed.

Minneapolis, Minn.-based medical device giant Medtronic Inc. has completed enrollment in the U.S. arm of its clinical study for the IN.PACT Admiral drug-eluting balloon. The balloons are intended as a treatment for peripheral artery disease in the superficial femoral and proximal popliteal arteries (SFA, the branch of the femoral artery closer to the skin and PPA, the extension of the SFA after passing through the lower third of the thigh and past the knee).

The study, IN.PACT SFA II, is a prospective, multi-center, randomized controlled trial that enrolled 181 patients at more than 40 sites in the United States, randomizing them 2:1 to treatment with either the IN.PACT Admiral drug-eluting balloon (study arm) or a traditional, non-coated angioplasty balloon (control arm). Its primary efficacy endpoint is primary patency, a measure of blood flow through the treated arterial segment, at 12 months.

The principal investigators of the trial are interventional cardiologist John Laird, M.D., professor of medicine at the University of California-Davis and medical director of the UC Davis Vascular Center; and vascular surgeon Peter Schneider, M.D., chief of the vascular therapy division at Kaiser Foundation Hospital and Hawaii Permanente Medical Group in Honolulu, Hawaii.

Results of IN.PACT SFA II will be combined with those from IN.PACT SFA I—which previously completed enrollment of 150 patients in Europe—to support a premarket approval application to the U.S. Food and Drug Administration (FDA).

“The European experience with IN.PACT drug-eluting balloons shows a promising interventional treatment for peripheral artery disease in the lower extremities,” said Prakash Krishnan, M.D., assistant professor of medicine and director of endovascular intervention at Mount Sinai Heart in New York, N.Y., and reportedly the highest enroller of patients in IN.PACT SFA II.

Results of European IN.PACT trials continue to be reported. For instance, the December 2012 issue of Circulation: Cardiovascular Interventions featured findings from the IN.PACT PACIFER (paclitaxel-coated balloons in femoral indication to defeat restenosis) trial.

According to published findings, the study met its primary endpoint by showing a statistically significant difference in reduction of late lumen loss (reduction in size of a blood vessel’s interior canal) at six months for the cases that used a drug-eluting balloon as compared to those that used a non-coated balloon. The PACIFIER trial defined major adverse events as death, amputation or target lesion revascularization. At 12 months, there were significantly fewer major adverse events in the study arm as compared to the control arm (7.1 percent versus 34.9 percent). All three of the major adverse events in the study arm were target lesion revascularizations (further percutaneous intervention at the lesion site); the control arm included 15 target lesion revascularizations and three deaths. None of the patients in the study had an amputation.

“With seven femoropopliteal trials featuring IN.PACT drug-eluting balloons presented at medical meetings and five of them already published in peer-reviewed journals, Medtronic is on track to deliver this technology to U.S. physicians in a timely manner with an unprecedented volume of high-quality clinical data to support its adoption,” said Tony Semedo, senior vice president of Medtronic and president of the company’s endovascular therapies business.

The ongoing global IN.PACT clinical program includes 29 studies involving more than 4,600 patients at approximately 230 sites worldwide. Through these company-sponsored and physician-initiated studies, Medtronic’s portfolio of IN.PACT drug-eluting balloons will be investigated thoroughly for the treatment of arterial disease in a variety of vessel beds. As part of this program, Medtronic currently is enrolling patients in the IN.PACT Global study, a “real-world” evaluation of the company’s IN.PACT drug-eluting balloons involving 1,500 patients with femoropopliteal lesions of any length at up to 80 sites worldwide.

IN.PACT drug-eluting balloons feature a coating called FreePac that is a formulation of paclitaxel and urea, an inactive vehicle that facilitates absorption of the drug into the vessel wall. These balloons received the CE mark in 2008 and 2009 and are available in many countries around the world, but not yet in the United States.

In the United States, the IN.PACT Admiral drug-eluting balloon is limited to investigational use under an investigational device exemption granted by the FDA and is not yet commercially available.

Other Medtronic Studies
Medtronic Inc. also kicked off two additional device trials in January. The first is Miracle EF, a global clinical trial that is evaluating the effectiveness of cardiac resynchronization therapy pacemakers (CRT-Ps) in delaying the progression of heart failure in symptomatic patients with mildly reduced heart pumping function. The second is Reveal AF, which through continuous cardiac monitoring will evaluate the incidence of atrial fibrillation (AF) among patients suspected to be at a high-risk for the disease, and is aimed at identifying key patient predictors for detection of AF.

In January, Medtronic enrolled its first patient in Miracle EF. This large study will be the first to evaluate CRT-P in a widely underserved patient group—those who have a slightly reduced left ventricular ejection fraction (LVEF) in the range of 36 to 50 percent, which means that their hearts work somewhat more efficiently than heart failure patients who currently are indicated for implanted device therapy because of their lower LVEF.

The CRT-P devices used in Miracle EF are not approved by the FDA for the patient population being studied. Edward Schloss, M.D., performed the first implant at The Christ Hospital’s Lindner Research Center in Cincinnati, Ohio. The primary investigator for the site is Greg Egnaczyk, M.D., Ph.D.

“Previous studies have proven the real-world therapeutic benefits of CRT in treating mildly to severely symptomatic heart failure patients with moderately to severely reduced cardiac pumping capacity and electrical dyssynchrony,” said Professor Cecilia Linde, M.D., Ph.D., of Karolinska University Hospital in Stockholm, Sweden, and worldwide principal investigator in the trial. “Through this large global study we hope to further our research on the overall effectiveness of CRT-P by showing its benefit in treating patients with mild-to-moderate heart failure symptoms, but with milder impairment of heart pumping capacity than previously studied.”

The trial will take place at approximately 275 centers throughout the world in regions including the United States, Canada, Europe, Japan and developing markets. The centers will enroll up to 2,300 patients who each will receive a Medtronic Consulta CRT-P in this prospective, double-blind, randomized controlled trial. The intention is that patients will be followed for at least two years or until the end of the study, which Medtronic estimates will take four to five years to complete. The effectiveness of the CRT-P in this patient population will be assessed using a composite endpoint of time to first event, defined as all-cause mortality or heart failure hospitalization.

“We are hopeful that, when completed, Miracle EF will influence clinical practice guidelines regarding the use of advanced cardiac resynchronization devices and potentially lead to another expanded indication for Medtronic CRT devices,” said David Steinhaus, M.D., vice president and general manager of heart failure, and medical director for the cardiac rhythm disease management business at Medtronic. “We look forward to the positive implications these findings could have on heart failure patients whose disease is less pronounced, yet who still experience symptoms and need advanced therapeutic solutions.”

Also in January, the first Reveal insertable cardiac monitor (ICM) was implanted in a Reveal AF trial participant. The ICM is a thin device implanted just beneath the skin that continuously records heart activity. The trial will assess how often patients experience atrial fibrillation that lasts six minutes or more, a key measure in determining the incidence of AF in the trial. The trial also will evaluate how physicians manage these patients once atrial fibrillation has been diagnosed, and will identify how the disease can be detected in patients earlier in the continuum of care.

“As a cardiologist I am quite concerned about the risks and complications of atrial arrhythmias, especially thromboembolic complications of atrial fibrillation,” said Eugene Parent, M.D., attending cardiologist and director of echocardiography at the Bradenton Cardiology Center and Manatee Memorial Hospital in Bradenton, Fla. “Frequently these rhythm changes are difficult to detect. The Reveal AF study will use the Reveal ICM to detect undiagnosed atrial fibrillation in patients at high risk for thromboembolic complications and allow more effective and prompt treatment of these patients.”

In the study, 400 patients from approximately 60 centers in the United States and Europe will be implanted with a Reveal ICM. The Reveal device is hoped to transmit information from the patient’s heart via Medtronic’s CareLink network, thereby allowing physicians to review patient data remotely. Each patient will be followed for a minimum of 18 months to monitor for atrial fibrillation and have in-office visits every six months.

“Atrial fibrillation is the most common arrhythmia, and with a five-fold increase in the risk of stroke, the condition carries significant burdens for patients, as well as on the healthcare system,” said Pat Mackin, president of the cardiac rhythm disease management business and senior vice president at Medtronic. “Through this study, Medtronic intends to show the clinical value of ICMs in detecting atrial fibrillation so that early-stage therapeutic decisions can be made to improve each patient’s quality of life.”

Atrial fibrillation is the most common heart arrhythmia, affecting more than 3 million Americans and 7 million people worldwide. The disorder can be difficult to diagnose, as it can occur infrequently and patients may not experience symptoms during an episode. Reveal’s around-the-clock monitoring, in contrast with intermittent, external monitoring, can result in earlier and more reliable diagnoses, which can lead to faster treatment, claims Medtronic.

Medtronic provides medical devices in a range of market segments including cardiovascular. The company is headquartered in Minneapolis, Minn.