Pam Harrison

June 17, 2014

AMSTERDAM — A new antithrombotic dialyzer (Evodial, Gambro) is at least as effective as standard techniques for providing heparin-free dialysis, and is less labor intensive, an international study shows.

Dialysis delivered through a heparin-grafted membrane, which obviates the need for anticoagulation, was significantly noninferior to the current standard of care of saline flushes or online predilution, said Maurice Laville, MD, from Lyon-Sud Hospital in France.

The HepZero study is the first large randomized controlled trial to compare strategies that do not involve heparin.

"Heparin is used in most patients on maintenance hemodialysis to prevent clotting," he said. "But some patients need to be dialyzed without anticoagulation because of high bleeding risk, and the methods used have high failure rates and increase work load because nurses have to monitor circuits for clotting."

"We hypothesized that the use of a heparin-grafted membrane could replace, and might even be superior to, the usual no-heparin methods for high bleeding-risk patients. We found that success with the [anticoagulant] dialyzer was significantly greater than the standard of care," he reported.

Dr. Laville presented the study results here at the European Renal Association-European Dialysis and Transplant Association 51st Congress.

HepZero Study

In the HepZero study, 265 patients who required heparin-free dialysis were randomized to the heparin-grafted membrane dialyzer or to one of the standard-of-care modalities — either regular saline flushes or online predilution — for up to 3 hemodialysis sessions.

The dialyzer contains a heparin-grafted polyacrylonitrile membrane. Preclinical work has shown that the heparin molecules remain stably bound to the dialyzer under clinical conditions and remain active throughout the dialysis session.

The most common indication for heparin-free dialysis was perioperative bleeding risk, the prevalence of which was similar in the 2 treatment groups, Dr. Laville reported.

Dialysis session parameters were controlled for and priming was done without heparin. The blood flow rate was at least 250 mL/min, and the expected duration of each dialysis session was 240 minutes.

A semiquantitative visual scale was used to assess clotting, from grade 1 (no detectable clotting) to grade 4 (complete occlusion rendering dialysis impossible).

"The primary objective of the study was to measure the effectiveness of the heparin-grafted membrane dialyzer and the standard of care in terms of the success of the first heparin-free session," Dr. Laville noted.

The first hemodialysis session was considered to be successful if all 4 of the following criteria were met: there was no complete occlusion of air traps or dialyzer, rendering dialysis impossible; there were no additional saline flushes to prevent clotting; there was no change of dialyzer or blood lines because of clotting; and there was no premature termination (early rinse-back) because of clotting.

Success Rate

The success rate was significantly greater with the heparin-grafted membrane dialyzer than with the standard of care (65% vs 59%). This resulted in an 18.2% difference between the 2 treatment groups (P = .005).

After adjustment for differences in dialysis centers, the absolute risk reduction was 21% with the dialyzer, compared with the standard of care. "This means that to avoid 1 dialysis failure, we only need to treat 5 patients, which is a very low number-needed-to-treat for a clinical study, " Dr. Laville explained.

The duration of dialysis was slightly longer in the dialyzer group than in the standard-of-care group (3.65 vs 3.45 hours). However, in successful sessions, there was no difference in the clotting rate between the 2 groups, or in the adverse event rate.

The removal of urea during dialysis was similar in the dialyzer and standard-of-care groups (1.15 vs 1.19 Kt/V).

"This is the first international open-label randomized controlled trial of heparin-free dialysis options in maintenance hemodialysis patients," Dr. Laville said.

"The success rate increased when using a heparin-grafted membrane. This difference was significant, firmly establishing the noninferiority of the heparin-grafted membrane dialyzer to the standard of care," he explained.

Setting the Scene for Larger Studies

It is "gratifying" to see research aimed at helping to refine the dialysis procedure, said Lynda Anne Szczech, MD, from Durham Nephrology Associates in North Carolina.

"To boldly restate the obvious, heparin has many downsides," she told Medscape Medical News. However, "because it has been the only anticoagulant strategy used on a large scale since the inception of dialysis, we have no way to truly appreciate the magnitude of these downsides."

"A thorough evaluation of this technology could really provide significant benefit to patients," she added.

The HepZero study addresses an important topic — how to improve dialysis for individuals with a high bleeding risk or other contraindication to anticoagulation, said Donal O'Donoghue, MB, ChB, professor of renal medicine at the University of Manchester and consultant renal physician at the Salford Royal NHS Foundation Trust in the United Kingdom.

"The increasing longevity and consequent multimorbidity in both the end-stage renal failure dialysis population and the general population within which acute kidney injury is increasingly seen has resulted in a step change in the number of individuals requiring dialysis who are at high risk of anticoagulant-precipitated bleeding," he said.

Thus, advances in this therapeutic area are "welcome," Dr. O'Donoghue added.

He cautioned that HepZero was not a large study, that the differences between the 2 treatment groups were modest, and that the study did not control for standard-of-care processes.

Nevertheless, "the study does provide a real-world evaluation [of the dialyzer], and suggests that improvements in efficiencies in care, and maybe even outcomes, will be possible using such technology."

Dr. O'Donoghue added that the HepZero study sets the scene for larger studies in a range of settings to establish the role of this technology in current patient care.

The HepZero study was sponsored by Gambro Lundia AB (Baxter International has completed the acquisition of Gambro AB). Dr. Laville is a member of the steering committee for the HepZero study. Dr. Szczech and Dr. O'Donoghue have disclosed no relevant financial relationships.

European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 51st Congress: Abstract MO036. Presented June 2, 2014.


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