PARIS – In the face of an expanded scope of scrutiny by French health authorities triggered by the death of the first patient in the pivotal trial for its artificial heart, Paris-based Carmat SA reported the suspension of the clinical study.

The company revealed the patient's death "was due to an interruption in the power supply system, following an incorrect battery handling by the patient, as a result of which the prosthesis stopped functioning."

Carmat confirmed that the prosthesis functioned correctly, which is consistent with the announcement in November 2016 that "analyses undertaken have not shown the prosthesis to be involved in the patient's death."

Though the company had said it would not reveal details from the pivotal trial until all data had been collected and analyzed, it was prompted to release this detail, "in order to rectify certain information published in today's press."

Following reports across the French media that the company was considering moving the pivotal trial to the U.S., Carmat's stock price on the Euronext Paris exchange tumbled more than 6 percent.

The report was based on an interview with Carmat CEO Stéphane Piat where he expressed frustration with the slowness of the National Agency for Safety of Medications and Health Products (ANSM) to authorize a continuation of the trial.

The company declined any comment beyond the statements in its press release.

Results from the PIVOT clinical study are critical for the company as the data combined with the company's technical file will be submitted for a CE mark approval that will authorize commercialization in Europe. (See Medical Device Daily, Feb. 29, 2016.)

In its announcement, Carmat said its support teams are actively working on the issue of battery handling "relating to post-operative monitoring in order to increase safety for the next patients."

The first PIVOT patient was implanted with the Carmat artificial heart at the end of August 2016, and his death was announced after only three months at the end of November 2016.

The company plans to enroll from 15 to 20 patients in the trial. Nine heart centers in France, Germany and Slovenia have completed training for the open-chest surgical procedure.

The company told Medical Device Daily that no other patients have been implanted with Carmat hearts as part of the PIVOT trial at centers outside of France, and only the one patient received the heart in France.

The endpoint for the PIVOT trial is six months and includes broader patient inclusion criteria than the four-patient safety-and-feasibility trial where only terminal stage patients could be recipients. Significantly the PIVOT inclusion criteria will enable patients who are eligible for a human heart transplant to participate.

The Carmat heart is a destination therapy and not a bridge to transplant, as the entire natural heart is removed and replaced with the 900 gram (2 pound) device.

Once the heart is implanted, only two wires exit the body at the abdomen, one to supply power to the self-regulating pump and the other to provide data on the device performance. The device is expected to give the same life expectancy as a transplanted human heart.

A unique feature of the Carmat heart, among other heart pumps, is a capability for self-regulating blood flow according to the patient's activity level, rather than a constant flow.

While this function was not used during the feasibility trial, Piat reported in the company announcement that during the three months the PIVOT patient survived, "the results provided by the self-regulating system used during the last implant have been very encouraging."

Explaining the suspension of the trial, the company said in its statement that discussion with ANSM showed the safety agency had expanded the scope of its analysis beyond what the company had anticipated.

"Given the nature of the remaining issues, Carmat was not in a position to meet the requirements within the stated time frame," it said in the announcement.

HOPING FOR A TRIAL RESTART

The company withdrew its request with ANSM to resume the PIVOT trial to allow more time to provide elements requested. The company added it intends to submit a new request for continuing the trial at a later date, a submission that will include the additional elements requested by the agency.

In the Carmat announcement, CEO Piat noted, "The prosthesis functioned normally during the last three implants, thus strengthening our incentive to provide a suitable response for patients facing total therapeutic stalemate."

Five men have received the Carmat heart, four with end-stage heart failure in the feasibility trial.

The inventor of the heart and co-founder of Carmat, Alain Carpentier, confirmed in The Lancet in July 2015 that the first patient died after 74 days as the result of a device failure. The second patient survived nine months, spending the last four at home until a malfunction in the heart ended his life.

The third patient also lived nine months and also was discharged from the hospital, but died of acute respiratory failure and chronic kidney failure. The fourth patient died from medical complications associated with his critical pre- and post-operative state, according to the company.

The primary unmet medical need for the Carmat heart is among the 90 percent of men with heart failure who are eligible for a human heart transplant but will not receive a heart as there is only one available for every 10 candidates. A second opportunity is for the half of all patients on ventricle assist devices who develop complications.