Two years after a 70-year-old retired construction worker became the first enrollee in the Fix Heart Failure 5 (FIX-HF-5) study by being implanted with the Optimizer III device from Impulse Dynamics (Orangeburg, New York), the company yesterday reported completion of patient enrollment in the trial.

The first patient was implanted with the device at St. Joseph’s Hospital (Atlanta) in April 2005 (Medical Device Daily, April 19, 2005).

The FIX-HF-5 study is the company’s largest randomized clinical trial to date and is intended to evaluate the safety and efficacy of the Optimizer, which is designed to deliver cardiac contractility modulation (CCM) non-excitatory impulses to treat patients with moderate to severe heart failure.

The Optimizer System is CE-marked and is an investigational device in the U.S.

The system consists of a pacemaker-like device and conventional pacing leads which are designed to sense electrical activity and deliver CCM therapy to the cardiac tissue. The device is implanted much like a pacemaker procedure, but compared to conventional pacing methods, the system uses the company’s CCM therapy in which electrical impulses are delivered to the heart after the heart has already initiated its contraction. And unlike conventional pacing signals, CCM is intended to increase the forcefulness of the heart’s pumping action rather than initiating a new contraction.

Daniel Burkhoff, MD, PhD, corporate VP and chief medical officer at Impulse Dynamics told Medical Device Daily that the FIX-HF-5 trial enrolled its last patient at the end of May, so the company has about a year of follow-up left before the study is complete.

“We’ll be focusing a lot of effort in ensuring the quality of data and data monitoring,” Burkhoff said.

After that is completed, Burkhoff said the company would spend another three to four months analyzing the data and then submitting it to the FDA for approval. Thus, it would be at least one year and nine months before the company is sitting in a panel meeting for the device.

Still, company officials emphasize that the enrollment of the last patient in the study is an important milestone.

Burkhoff said the study focused on patients who have been taking all the approved drugs to treat heart failure, but are still having symptoms of Class III or Class IV heart failure and who are not currently eligible for any other therapies. He said the trial excluded patients who have an indication for cardiac resynchronization therapy (CRT).

“In contrast to other device-based therapies for heart failure, such as [CRT], this study is focused on those patients without evidence of ventricular dyssynchrony. Patients with symptomatic heart failure without dyssynchrony currently have few treatment options,” said Yuval Mika, MD, chief operating officer of Impulse Dynamics.

More than 50 investigational sites across the U.S. are participating in the FIX-HF-5 study. These sites enrolled more than 760 patients and randomized nearly 430 patients in a two-year period.

“We have been very active in this trial and are committed to offering our patients the newest treatment options available,” said Steven Krueger, MD, director of the Heart Improvement Program, Bryan LGH Heart Institute (Lincoln, Nebraska) and a lead FIX-HF-5 enroller. “We believe that CCM therapy has an effect on the cellular level. This is a novel approach with the potential to help many patients without alternative treatments.”

According to the company, functional assessments made at baseline and throughout the follow-up period include cardiopulmonary treadmill exercise testing, six-minute walk test, NYHA classification, and quality-of-life scoring. An independent Data and Safety Monitoring Board are also monitoring safety variables such as the rate and cause of hospitalizations and deaths, the company noted.

“The Optimizer System with CCM Therapy is an exciting approach with the potential to treat those patients with Class III or Class IV heart failure, despite treatment with standard drug therapies, who presently have no other options,” said William Abraham, MD, chief of the Division of Cardiovascular Medicine, at Ohio State University (Columbus, Ohio) and FIX-HF-5 co-principal investigator. “The primary value here lies in the fact that the device is intended to improve the strength of the heart beat without adding to its overall workload. The combination of improved strength and increased efficiency of the heart makes us very optimistic about this particular therapy.”

The device received a boost last September with the report of positive clinical trial data at the 10th annual scientific meeting of the Heart Failure Society of America ’s (HFSA; St. Paul, Minnesota), in Seattle (MDD, Sept. 13, 2006). Those results, however, involved a separate European trial evaluating CCM called FIX-4. The FIX-4 data indicated that the Optimizer enhances exercise tolerance and improves quality-of-life.

“The completion of the FIX-HF-5 trial enrollment will substantially add to the growing body of evidence evaluating CCM therapy,” said Alan Kadish, MD, a professor in the Division of Cardiology at Northwestern University (Chicago) and FIX-HF-5 co-principal investigator. “Unlike other cardiac devices for heart failure like pacemakers and defibrillators, the Optimizer System is designed to modulate the strength of contraction of the heart muscle rather than its rhythm. It is always important to consider and evaluate new heart failure therapies in order to do everything possible to potentially improve the lives of patients with this debilitating disease.”

Heart failure is a disease caused by a weak or damaged heart muscle that is unable to pump enough blood throughout the body, the company noted, adding that nearly 5 million Americans are living with the disease, and 550,000 new cases are diagnosed each year. It is also one of the most common causes of hospitalization and a growing and costly burden to the healthcare system. According to Impulse, it is estimated that the U.S. healthcare system will spend more than $20 billion in related costs for the treatment of heart failure patients in 2007.

The company is focused on the development of electrical therapies for the treatment of heart failure. It says that its technology stems from a scientific discovery regarding the electrical control of tissue function.