title: Rationale and design of the HepZero study: a prospective, multicenter, international, open, randomized, controlled clinical study with parallel groups comparing heparin-free dialysis with heparin-coated dialysis membrane (Evodial) versus standard care: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Anticoagulation for chronic dialysis patients with contraindications to heparin administration is challenging. Current guidelines state that in patients with increased bleeding risks, strategies that can induce systemic anticoagulation should be avoided. Heparin-free dialysis using intermittent saline flushes is widely adopted as the method of choice for patients at risk of bleeding, although on-line blood predilution may also be used. A new dialyzer, Evodial (Gambro, Lund, Sweden), is grafted with unfractionated heparin during the manufacturing process and may allow safe and efficient heparin-free hemodialysis sessions. In the present trial, Evodial was compared to standard care with either saline flushes or blood predilution.
  
  
  METHODS
  The HepZero study is the first international (seven countries), multicenter (10 centers), randomized, controlled, open-label, non-inferiority (and if applicable subsequently, superiority) trial with two parallel groups, comprising 252 end-stage renal disease patients treated by maintenance hemodialysis for at least 3 months and requiring heparin-free dialysis treatments. Patients will be treated during a maximum of three heparin-free dialysis treatments with either saline flushes or blood predilution (control group), or Evodial. The first heparin-free dialysis treatment will be considered successful when there is: no complete occlusion of air traps or dialyzer rendering dialysis impossible; no additional saline flushes to prevent clotting; no change of dialyzer or blood lines because of clotting; and no premature termination (early rinse-back) because of clotting.The primary objectives of the study are to determine the effectiveness of the Evodial dialyzer, compared with standard care in terms of successful treatments during the first heparin-free dialysis. If the non-inferiority of Evodial is demonstrated then the superiority of Evodial over standard care will be tested. The HepZero study results may have major clinical implications for patient care.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01318486.
authors.affiliation: INSERM, Centre d'Investigations Cliniques 9501, Institut lorrain du Cœur et des Vaisseaux Louis Mathieu, Vandoeuvre lès Nancy, France. p.rossignol@chu-nancy.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Marc
authors.initials: M
authors.lastname: Dorval
authors.forename: Renaud
authors.initials: R
authors.lastname: Fay
authors.forename: Joan Fort
authors.initials: JF
authors.lastname: Ros
authors.forename: Nathalie
authors.initials: N
authors.lastname: Loughraieb
authors.forename: Frédérique
authors.initials: F
authors.lastname: Moureau
authors.forename: Maurice
authors.initials: M
authors.lastname: Laville
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects; D002985:Clinical Protocols; D020099:Coated Materials, Biocompatible; D004867:Equipment Design; D004868:Equipment Failure; D005060:Europe; D006438:Hemodilution; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D008567:Membranes, Artificial; D011446:Prospective Studies; D006435:Renal Dialysis / Q000295:instrumentation*; D012107:Research Design; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D020099:Coated Materials, Biocompatible; D008567:Membranes, Artificial; D012965:Sodium Chloride; D006493:Heparin