NATIONAL HARBOR, MD. – The trial designed to definitively test the safety and efficacy of ultrafiltration as an alternative to intravenous diuretics for patients hospitalized with acute decompensated heart failure got cut to about a quarter of its planned enrollment by the company that recently acquired the ultrafiltration technology. This outcomes means that ultrafiltration’s role in acute heart failure remains uncertain and will stay that way for the foreseeable future.
As a consequence, ultrafiltration (also known as aquapheresis), approved for use in the United States by the Food and Drug Administration in 2002, will be used by believers in the treatment on some of the estimated 200,000 or more U.S. heart failure patients who become hospitalized each year with acute, severe congestion that is unresponsive to diuretic treatment. Other clinicians who remain skeptical of ultrafiltration’s safety and efficacy will not use it, and currently no prospect remains to resolve this uncertainty. Also limiting ultrafiltration’s use is its designation as investigational by U.S. health insurers.
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“Early termination off the AVOID-HF [Aquapheresis Vs. Intravenous Diuretics and Hospitalization for Heart Failure] trial was a tragedy because it is unlikely we will ever see a trial of its size again,” commented Dr. G. Michael Felker during a discussion of treatment for acute heart failure at the at the annual meeting of the Heart Failure Society of America. “We still have no definitive answer” about ultrafiltration,” said Dr. Felker, professor of medicine and a cardiologist specializing in acute heart failure at Duke University in Durham, N.C.
Opinions about ultrafiltration and its role in treating patients with acute decompensated heart failure remain sharply split, although at this point, even proponents of the treatment concede that its use is limited to severely congested decompensated heart failure patients who prove unresponsive to intravenous diuretic therapy.
Mitchel L. Zoler/Frontline Medical News
Dr. G. Michael Felker
Ultrafiltration is for patients with “recurrent decompensation (not the first episode) and a large amount of fluid overload (more than 10 pounds) who also have elevated central venous pressure and elevated abdominal pressure that reduces blood flow to the kidneys,” Dr. Maria Rosa Costanzo said in a video interview. Used in these patients at a low rate of 20-50 cc/hour to “gently remove fluid,” the treatment reduces central venous and intra-abdominal pressures, leading to increased urine output and restoration of diuretic sensitivity, said Dr. Costanzo, lead investigator for the AVOID-HF trial and medical director of the heart failure and pulmonary hypertension program at the Advocate Heart Institute in Naperville, Ill.
A dramatically opposing view of ultrafiltration came from Dr. Christopher M. O’Connor, a heart failure cardiologist and CEO of the Inova Heart and Vascular Institute in Falls Church, Va.
“Even in diuretic-resistant, patients I would not use ultrafiltration. It does not anymore fit into management” of acute decompensated heart failure patients, Dr. O’Connor said in an interview. The CARRESS-HF [Cardiorenal Rescue Study in Acute Decompensated Heart Failure] trial targeted patients with diuretic resistance, the very population we would need to treat, and we did not see an advantage to ultrafiltration,” said Dr. O’Connor, a coinvestigator on CARRESS-HF, an earlier trial that compared the two treatment methods (N Engl J Med. 2012 Dec 13;367[24]:2296-304).
“We need to understand who is the right patient” for ultrafiltration. “We need to continue to investigate [ultrafiltration] to know where it best fits,” commented Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago.
Mitchel L. Zoler/Frontline Medical News
Dr. Clyde W. Yancy
AVOID-HF enrolled and randomized 224 patients with acute decompensated heart failure out of an anticipated enrollment of 810 patients. Analysis of the study’s primary endpoint, time to first heart failure event within the first 90 days following hospital discharge, occurred after an average of 34 days in 108 loop-diuretic treated patients and after an average 62 days in 105 ultrafiltration-treated patients, a difference that did not achieve statistical significance. A heart failure event within the first 90 days occurred in 25% of the ultrafiltration patients and in 35% of those on diuretic treatment, also a nonsignificant difference, Dr. Costanzo reported. Concurrent with her report at the meeting an article appeared online with the results (JACC Heart Fail. 2015;doi: 10.1016/j.jchf.2015.08.005).
Increases in serum creatinine were modest following ultrafiltration and similar to changes seen in the patients who received loop diuretic treatment. The biggest rise in average serum creatinine level occurred at 30 days after randomization, with an average 0.37 mg/dL rise among the ultrafiltration patients.
The abrupt shutdown in the AVOID-HF trial occurred following a change in ownership of the ultrafiltration technology used in the study. Ultrafiltration had been initially developed by CHF Solutions of Brooklyn Park, Minn. In 2010, Gambro, a Swedish company, acquired CHF Solutions and rights to the ultrafiltration system, and Gambro initiated the AVOID-HF trial. Baxter, in Deerfield, Ill., acquired Gambro in September 2013, and in April 2014, Baxter stopped the AVOID-HF trial because of slow projected enrollment, said Dr. Costanzo. But she strongly disagreed with this projection, and said that the trial showed no signs of futility or safety concerns when it came to a stop. Getting the data from Baxter to allow her and her associates to write their report and deliver their findings at the meeting took a lot of persuasion, Dr. Costanzo added.