Pharmaceutical

The events leading up to the sudden death warning with GranuFlo dialysis product

Fresenius sign The events leading up to the sudden death warning with GranuFlo dialysis productWhat occurred within Fresenius Medical Care (FMC), the world’s largest provider of dialysis products and services?

RenalWEB sought to find the answer to that question in the second part of a two-part series looking into the high number of cardiovascular-related deaths in dialysis patients allegedly tied to GranuFlo, a product made by Fresenius and used during hemodialysis treatments. The first story in the series explained the problem.

GranuFlo, a dry acid concentrate, contains an ingredient that converts to bicarbonate in the body. Elevated levels of bicarbonate have been linked to cardiovascular events, including sudden cardiac death. GranuFlo contains more of this ingredient than competitor products.

In November 2011 Fresenius warned doctors in its clinics to be aware of this when they prescribe the product to patients, as this may be contributing to patient deaths. The company failed to warn doctors at non-Fresenius clinics where GranuFlo is used, nor did they warn patients of this grave risk, until four months later — after someone anonymously sent the Food and Drug Administration (FDA) a copy of the internal memo.

Part 2 of RenalWEB’s series on Fresenius focuses on what led the company to identify GranuFlo as the culprit. According to the report: “In April 2009, a 4-day conference titled ‘ESRD: State of the Art and Charting the Challenges for the Future’ was held in Boston. The main purpose of the conference was to address the lack of improvement in dialysis patient survival over the last twenty years. At that meeting, sudden cardiac death was identified as the No.1 cause of death for dialysis patients, accounting for 59 percent of cardiovascular-related deaths.”As a result of the conference, several leading nephrologists reduced sodium levels in dialysate and made other adjustments in the fluids given to dialysis patients.

One of the steering members of the conference was Raymond Hakim, MD, PhD, who was Chief Medical Officer of Fresenius Medical Care North America (FMC) at the time. The conference discussions on sudden cardiac death seem to have prompted the company to investigate cases of cardiopulmonary arrest in patients at its own dialysis facilities between Jan. 1, 2010, and Dec.31, 2010.

What they found was 941 patients in 667 FMC facilities had cardiopulmonary arrests while being treated at FMC dialysis clinics. They found that patients who had elevated pre-dialysis bicarbonate levels were 4.7 to 6.3 times higher risk of cardiac arrest. This report led FMC to warn doctors of the possibility of dosing errors with its dialysate product GranuFlo.

Though the memo was not signed by Hakim, then chief medical director of FMC, RenalWEB speculates that “he was likely responsible for the FMS internal memo released on that date. As Chief Medical Officer, it would seem logical that Dr. Hakim would also notify his non-physician superiors at FMC, Ben Lipps and (Mau)Rice Powell, of his decision to release the Nov 4, 2011, internal FMC memo. He would likely also have recommended that the medical products division of FMC notify their other customers, the non-FMC clinics, of the FMS findings so these non-FMC clinics could make the best decisions for their patients regarding the use of Granuflo.”

Six days after the FMC sent the internal memo warning, Hakim attended the annual meeting of the American Society of Nephrology (ASN), during which a study was presented that indicated elevated bicarbonate levels in dialysis patients increased the risk of patient death.

“It appears that Dr. Hakim left Philadelphia more convinced than ever that non-FMC clinics needed to be notified of his finding concerning Granuflo, alkalosis, and (cardiopulmonary) arrests. It would seem logical that Dr. Hakim would become more adamant in his requests that the product division of FMC do this as soon as possible,” the RenalWEB story speculates.

However, a week later, Fresenius issued a press release stating that Hakim was stepping down as Chief Medical Officer. It would take another four months for others to be warned of the sudden death risks with GranuFlo, and then only after the internal memo was leaked to the FDA.

According to RenalWEB, “Currently there are over 5700 dialysis centers and approximately 400,000 dialysis patients in the United States. It is estimated that 3300 of these clinics use Granuflo formulations and that approximately 260,000 patients are using the product. It is estimated that slightly less than half these patients, or approximately 125,000 patients, are using Granuflo in non-FMC clinics. Total revenues from Granuflo sales per year in the U.S. are estimated at a minimum of $80 million.”

Source: RenalWEB