Evaluation of the efficacy of an interdialytic "ethanol 40% v/v - enoxaparin 1000 U/mL" lock solution to prevent tunnelled catheter infections in chronic hemodialysis patients: a multi-centre, randomized, single blind, parallel group study

Abstract

Background: Tunnelled dialysis catheter (TC) infections are a major health complication and are associated with increased antibiotic consumption, hospital stays, health costs and mortality. Experimental data provide evidence that Ethenox, a mixture of enoxaparine 1000 U/mL in 40% v/v ethanol, could be a promising lock solution. The aim of the study is to compare an interdialytic lock solution of Ethenox with reference lock solutions, unfractionated heparin (UFH) or citrate 4% for the prevention of TCI in hemodialysis patients.

Method: This study will monitor a multicentre, prospective, single blind, randomized, controlled, parallel group trial. The main inclusion criteria are patients > 18 years old with end-stage renal disease, treated with chronic hemodialysis/hemodiafiltration three times a week, with incident or prevalent non-impregnated internal jugular TCs inserted for at least 2 weeks and able to give informed consent. Exclusion criteria are TCI in the previous 4 weeks and anti-infective treatment for TCI in the previous 2 weeks. Patients will be randomized to receive either study treatment Ethenox in the intervention group or reference solutions in the control group, unfractionated heparin (UFH) or citrate 4% w/v according to usual practice. The primary outcome measure will be time to first TCIs assessed by an endpoint adjudication committee blinded to the study arm according to predefined criteria. Patients will receive the study treatment for up to 12 months. Intention-to-treat analysis of the primary endpoint will be performed with a marginal Cox proportional hazard model. Prospective power calculations indicate that the study will have 90% statistical power to detect a clinical significant two-fold increase in median infection-free survival if 200 patients are recruited into each arm over a period of 24 months.

Discussion: Firm evidence of the efficacy of the Ethenox lock in preventing TCI could be of major clinical benefit for patients. The results of this study will allow the development of new guidelines based on a high level of evidence.

Trial registration: ClinicalTrials.gov Identifier: NCT03083184 , date of registration March 17 2017 and European Clinical Trials Database Identifier: EudraCT 2016-A00180-51), date of registration July 11 2016.

Keywords: Catheter; Ethanol; Hemodialysis; Infection; Lock; Low molecular weight heparin; Tunnelled.

Conflict of interest statement

Ethics approval and consent to participate

The protocol, the information and consent forms, and the investigator’s brochure on Ethenox have received authorization from the “cpp-sudest6” (AU 1269) ethics committee and the Agence National de Sécurité du Médicament et des produits de santé (ANSM) (2016-A00180-51). The investigator explain the study to the patient and give him/her the information form. The patients willing to participate in the study sign a written consent form.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Schema for the Eternity trial. Enrolled patients will be randomly assigned in a 1:1 ratio either to the intervention group (Ethenox) or to the control group (reference solution: UFH 5000 U/mL or citrate 4% w/v depending on which solution is generally used). Random allocation will be performed by minimization using a computer algorithm. The study will be performed single blind for the patients and the analysts. The primary outcome will be time to first TCIs assessed by an endpoint adjudication committee blinded from study arm according to predefined criteria

Fig. 2

Scheme of participation in the study for a patient. TC is the statististical unit and several consecutive TC will be analysed in a same patient from the time the inclusion criteria are fullfilled