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 (ETERNITY)

In France, a central venous catheter is used in 20 to 30% of chronic hemodialysis patients as the vascular access device. In this patient population the recommended device is a tunnelled dialysis catheter (TC). TC-related infections (TCI) and TC dysfunctions are two major complications and are associated with increased antibiotic consumption, hospital stays, health costs and mortality. Strategies to prevent TCI should target endoluminal biofilm formation, which is the major cause of long-term catheter colonization.

Unfractionated heparin (UFH), 5000 U/mL, is the standard interdialytic lock solution for the prevention of TC thrombosis. A lower-UFH concentration (1000U/mL) is associated with similar catheter patency. However, UFH has no antibiofilm properties. Antibiotic locks decrease the rate of TCI including TC- related bloodstream infections (TCBSI) and exit-site infection (ESI). The widespread use of antibiotic lock solutions raises concerns, however, because of side effects and the risk for the development of antimicrobial-resistant microorganisms.

Ethanol is an inexpensive antiseptic agent with activity against a broad range of bacteria and fungi commonly involved in TCI. It acts by non-specific protein denaturation and thus is less likely to promote antimicrobial resistance. Ethanol concentration of 40% v/v is highly effective in eradicating biofilm and has no significant impact on the integrity of silicone and polyurethane TCs or on their mechanical properties. A small randomized controlled trial performed in chronic hemodialysis patients with TC suggests that once-weekly instillation of an interdialytic ethanol lock is effective in preventing TCBSI. However, ethanol has no anticoagulant properties and may induce TC dysfunctions when used alone.

Experimental data provide evidence that a combined solution of ethanol and injectable anticoagulant is a promising lock solution for preventing both TC infections and dysfunctions. UFH, at whatever concentration, cannot be mixed with ethanol 40% v/v because of precipitation. ERA-EDTA recommends using low molecular weight heparins (LMWHs) for blood circuit anticoagulation during dialysis sessions. Like UFH, LMWHs have no antibiofilm properties. In contrast, LMWHs can be mixed in ethanol 40% v/v with enoxaparin having the highest solubility, up to 1300 U/mL. Our group demonstrated that ethanol 40% v/v - enoxaparin 400 U/mL is stable, compatible with TC materials and exhibits antibiofilm and anticoagulant properties in vitro (patent). No clinical studies have previously assessed the efficacy of a combined solution of ethanol and LMWH in preventing TCI in chronic hemodialysis patients.

Screening Patients eligible to participate in the study will be identified by a clinical research assistant in each study centre at the beginning of the study and then weekly. Data recorded in the medical records will be used.