Despite clear data shortcomings, an FDA advisory committee half-heartedly recommended approval in an 11 to 5 vote for St. Jude Medical’s heart closure device Amplatzer to treat stroke.
The panel homed in on the problems and limitations of the RESPECT trials, stating the eight year study was statistically underpowered and therefore clinically invalid. Specifically, the studies failed to show a reduced rate of strokes for patients implanted with the Amplatzer compared to antiplatelet therapy.
Panelists also highlighted the change in clinical trial design between 2000 and 2016, noting that the methods and procedures used underpowered the trial, and a new study with tighter parameters should be conducted.
But Bram Zuckerman, director of the Division of Cardiovascular Devices said the FDA was not going to “throw the baby out with the bath water,” and nullify all the work done in the RESPECT trials. Instead, the agency would coax out what was learned from the trial about individualized risk-factors, he said.
“There is no single standard of care anti-thrombotic medical therapy to reduce the risk of recurrent stroke in patients with cryptogenic stroke,” the FDA said in briefing documents.
The agency added that the use of multiple combinations of anti-thrombotic agents also presented challenges in “defining the probable benefits of the device versus medical therapy.”
The patent foramen ovale (PFO) occluder is intended to put a stopper on blood shunting across the PFO, which can potentially lead to recurrent ischemic strokes.
In spite of heated debate over the indication and patient population, the committee ultimately agreed that the Amplatzer should be restricted to percutaneous, transcatheter closure of a PFO to prevent recurrent ischemic stroke in patients who have had a cryptogenic stroke due to presumed paradoxical embolism.
Members of the agency’s Circulatory Systems Devices Panel of the Medical Devices Advisory Committee also voted on the safety, effectiveness and risk to benefit ratio for the device. The panel voted 15 to 1 on the safety, 9 to 7 on the effectiveness and 11 to 5 stating the benefits outweighed the risks.
The FDA identified several major problems with the Amplatzer study, stating “missing data is more influential than the data presented.”
The panel said its approval should be contingent upon the FDA and sponsors conducting additional work to identify the selective group of patients who would benefit most. The group also recommended adding rigorous criteria on the proposed label as well as further postmarket analysis.
Earlier this month, panel chair Richard Page was granted a waiver to participate in the advisory committee meeting as a non-voting participant (). Page said he would have voted in favor of the safety of the device, but would have voted no for effectiveness and risk versus benefits.
The RESPECT study began in 2003, enrolling 980 patients who were randomized to either PFO closure or medical therapy alone. The patients were followed up for 2.5 years, and showed a 51 percent reduced risk of recurrent stroke in the device group.
St. Jude inherited the device when it acquired AGA Medical in 2010. There is little doubt the news will be greeted by Abbott, which agreed to acquire St. Jude Medical for $25 billion in a cardiovascular device market megamerger earlier this month (). — Joya Patel