It was a week of highlights for Direct Flow Medical (Santa Rosa, California), a transcatheter heart valve company. The company not only scored an investigational device exemption approval from the FDA for its transcatheter aortic valve system, but also reported what it said was strong data from the DISCOVER CE mark trial.
The company's transcatheter aortic valve system is designed to treat patients with severe aortic stenosis who are at extreme surgical risk, while reducing the risk of post-procedural aortic regurgitation, a strong predictor of long-term mortality. The system addresses this clinical concern by sealing the annulus and enabling complete assessment of hemodynamic performance with unlimited repositioning of the valve after full deployment. The system avoids rapid pacing of the heart during deployment and post-dilatation following placement, minimizing the risk of hemodynamic instability for patients.
The device incorporates a polymer frame, which is expanded using pressurized saline and contrast for placement, assessment and repositioning. The saline/contrast solution is easily exchanged for a quick-curing polymer that solidifies and secures the valve in place once optimal positioning is reached. The double-ring design of the valve creates a tight seal around the annulus. The system is fully repositionable and retrievable up until polymer exchange. The metal-free design enables a low-profile (18 French), fully sheathed delivery system for all valve sizes that minimizes vascular complications.
"Following some very strong data from the DISCOVER trial and the feasibility trial, and from the initial commercial experience which has mirrored clinical trials, we have recently received approval from the FDA to move forward with a pivotal trial for approval in the U.S.," Charles Davidson, MD, chief medical officer of the company, told Medical Device Daily.
The SALUS trial is a prospective, non-randomized, multi-center, core lab-adjudicated clinical trial evaluating the system at up to 30 sites. The primary endpoint of the trial is a composite of all-cause mortality and disabling stroke at 12 months. Principal investigators for the SALUS trial are Murat Tuzcu, MD, vice chairman of the department of cardiology at the Cleveland Clinic, and Patrick McCarthy, MD, director of the Bluhm Cardiovascular Institute and chief of cardiac surgery, Northwestern Memorial Hospital (Chicago).
"We're going to begin enrollment within the next few weeks," Davidson said. "We anticipate nearly a year of enrollment and then typically need a year of follow up. That brings us out to about two and a half years for potential approval in the U.S."
An earlier feasibility phase of the SALUS trial conducted in 2013 evaluated the system in 30 patients. The 30-day outcomes demonstrated a survival rate of 97%, low procedural complications, no incidence of stroke, a 3% rate of permanent pacing and 100% of patients with mild or less aortic regurgitation. The mean aortic gradient decreased from 44.5 mmHg to 12.7 mmHg at 30 days.
Although the Direct Flow system does not have approval in the U.S., it does have approval in Europe. The company said that the device received the CE mark in January 2013.
The company reported 12-month outcomes from the DISCOVER trial, which was used to gain CE mark approval in Europe. In the trial, a 90% survival rate was reported, continuing the initial positive trend of 99% survival after 30 days. Patients were treated with the Direct Flow system and experienced excellent overall hemodynamic results as well as a low rate of procedural complications. At 12 months, 100% of patients experienced mild or less aortic regurgitation (AR), with 77% having none or trace AR.
In the DISCOVER trial, the mean transthoracic echo gradient at 30 days was 12.5mmHg and remained low at 12 months (12.3mmHg). All hemodynamic outcomes were assessed and reported by an independent imaging core laboratory. The VARC-defined device success rate was 91%. At 30 days, 83% of patients had improved by more than one New York Heart Association (NYHA) functional class and this was maintained at 12 months, with 95% classified as NYHA Class I/II.
"The [DISCOVER] data will be used in support of the data that will be collected in a U.S. trial," Davidson said. "But it will not be used in lieu of the planned U.S. trial. The big part is that the one year data was very strong as far as freedom from death and freedom from stroke - near 90%."