Baxter's ($BAX) suspension of a randomized clinical trial of adjustable ultrafiltration to treat heart failure has proven unpopular with study investigators and subject matter experts, who described the move as premature and unilateral in the Journal of the American College of Cardiology.
The goal was to determine whether fluid removal via procedural ultrafiltration prolonged the onset of the first heart failure event within 90 days of hospitalization as compared to standard diuretic drugs. Among the 224 patients (out of a planned 810), a heart failure event occurred in 25% of the ultrafiltration patients, compared to 35% in the control (or drug only) arm.
Also known as aquapheresis, ultrafiltration involves the use of a hemofilter to remove fluid from a patient's blood. Only small particles of the patients' blood fit through the filter's pores. The purified blood is then returned the patient's body.
Baxter told the investigators it suspended the study April 2014 because of slower than expected enrollment. "The Steering Committee disagreed with the Sponsor's decision. The termination of the trial was in no way related to signals of futility or safety concerns," wrote the study investigators in their paper in the JACC.
Principal investigator and study co-author Dr. Maria Rosa Costanzo described the tantalizing signs of promise from the still-unproven procedural approach, saying that "patients who derive the greatest benefit are those who have the greatest fluid overload--those with 10 or more pounds weight gain," in an interview with Medscape.
"I also found it very useful in patients who have right ventricular dysfunction, because the action of diuretics in those patients is unpredictable," Costanzo continued.
She added that by reducing central venous pressure and intra-abdominal pressure, sensitivity to diuretics is restored, enabling smaller dosages.
Meanwhile, Dr. Daniel Mark and Dr. Christopher O'Connor wrote in an accompanying editorial in the JACC that Baxter's decision was made for financial (not clinical) reasons, and said that the case raises broader ethical questions about the clash of business and science: "As soon as the sponsor makes the decision to prematurely terminate a study for business reasons, with no scientific or safety concerns, the ethical grounds used to justify enrollment of patients into the trial up to that point is erased: the patients already enrolled accepted the risks of the trial; the benefits may no longer be obtainable."
But the doctors stopped short of tearing into Baxter. "If we try to compel companies to satisfy abstract societal goals over their own motivations, what might be the unintended consequences?" they asked.
The doctors wrote that the cancelation of the trial is disappointing, but concluded that "the trial (AVOID-HF) does not offer a clear 'teachable moment' regarding sponsor ethical misconduct. In our current regulatory environment, with the very high cost of bringing new therapies to market, our best defense against more AVOID-HF cases is to only start trials that are designed efficiently, budgeted adequately, and clearly feasible in terms of enrollment targets. If we can achieve that, we will have done much to ensure that the contribution of patients enrolling in our trials is not wasted."
Baxter entered the investigational ultrafiltration arena with the purchase of dialysis competitor Gambro for $3.9 billion in 2013. The company did not respond to a request for comment by the publication deadline.
For the foreseeable future, it appears that the device industry's contribution to fluid buildup as it relates to heart failure will remain restricted patient monitoring, as exemplified by St. Jude's ($STJ) CardioMEMS implantable heart failure monitor. Israel's Kyma Medical Technologies was recently acquired by Zoll Medical for $35 million after it obtained a CE mark for a wearable remote monitoring device for the condition.
- read the study in the JACC (PDF) | here's the editorial (PDF)
- here's MedScape's take (reg. req.)
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