PMID- 31039759 OWN - NLM STAT- MEDLINE DCOM- 20200605 LR - 20231011 IS - 1471-2369 (Electronic) IS - 1471-2369 (Linking) VI - 20 IP - 1 DP - 2019 Apr 30 TI - 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. PG - 149 LID - 10.1186/s12882-019-1338-6 [doi] LID - 149 AB - 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. FAU - Aniort, Julien AU - Aniort J AUID- ORCID: 0000-0001-9541-1264 AD - Nephrology, Dialysis and Transplantation Department, Gabriel Montpied University Hospital, 54 rue Montalembert, BP69, 63003, Clermont-Ferrand, Cedex 1, France. janiort@chu-clermontferrand.fr. FAU - Piraud, Aurelien AU - Piraud A AD - Nephrology, Dialysis and Transplantation Department, Gabriel Montpied University Hospital, 54 rue Montalembert, BP69, 63003, Clermont-Ferrand, Cedex 1, France. FAU - Adda, Mireille AU - Adda M AD - Medical Intensive Care Unit, Gabriel Montpied University Hospital, Clermont-Ferrand, France. FAU - Perreira, Bruno AU - Perreira B AD - Biostatistics Unit (DRCI), University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. FAU - Bouiller, Marc AU - Bouiller M AD - Nephrology and Dialysis Department, Emile Roux Hospital, Le Puy en Velay, France. FAU - Fourcade, Jacques AU - Fourcade J AD - Nephrology and Dialysis Department, Metropole-Savoie Hospital, Chambery, France. FAU - Guerraoui, Abdallah AU - Guerraoui A AD - Calydial Viennes, Vienne, France. FAU - Kalbacher, Emilie AU - Kalbacher E AD - Nephrology and Dialysis Department, Edouard Herriot University Hospital, Lyon, France. FAU - Krumel, Thierry AU - Krumel T AD - Nephrology and Dialysis Department, University Hospital, Strasbourg, France. FAU - Moragues, Helene Leray AU - Moragues HL AD - AIDER, Montpellier, France. FAU - Thibaudin, Damien AU - Thibaudin D AD - Nephrology and Dialysis Department, University Hospital, Saint Etienne, France. FAU - Vela, Carlos Gustavo AU - Vela CG AD - Nephrology and Dialysis Department, Hospital, Perpignan, France. FAU - Vernin, Guillaume AU - Vernin G AD - AGDUC, La Tronche, France. FAU - Weclawiak, Hugo AU - Weclawiak H AD - Nephrology and Dialysis Department, Medipole Saint-Roch Clinic, Cabestany, France. FAU - Bernard, Lise AU - Bernard L AD - Pharmacy department, Gabriel Montpied University Hospital, Clermont-Ferrand, France. FAU - Heng, Anne Elisabeth AU - Heng AE AD - Nephrology, Dialysis and Transplantation Department, Gabriel Montpied University Hospital, 54 rue Montalembert, BP69, 63003, Clermont-Ferrand, Cedex 1, France. FAU - Souweine, Bertrand AU - Souweine B AD - Medical Intensive Care Unit, Gabriel Montpied University Hospital, Clermont-Ferrand, France. AD - CNRS UMR 6023, Laboratoire Microorganismes: Genome et Environnement, Universite Clermont-Auvergne, Clermont-Ferrand, France. LA - eng SI - ClinicalTrials.gov/NCT03083184 SI - EudraCT/EudraCT 2016-A00180-51 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190430 PL - England TA - BMC Nephrol JT - BMC nephrology JID - 100967793 RN - 0 (Anti-Infective Agents, Local) RN - 0 (Drug Combinations) RN - 0 (Enoxaparin) RN - 0 (Fibrinolytic Agents) RN - 3K9958V90M (Ethanol) SB - IM MH - Adult MH - Anti-Infective Agents, Local/*administration & dosage MH - Catheter-Related Infections/*prevention & control MH - Catheters, Indwelling/adverse effects MH - Clinical Trials, Phase III as Topic MH - Disease-Free Survival MH - Drug Combinations MH - Enoxaparin/*administration & dosage MH - Ethanol/*administration & dosage MH - Fibrinolytic Agents/*administration & dosage MH - France MH - Humans MH - Intention to Treat Analysis MH - Jugular Veins MH - Kidney Failure, Chronic/therapy MH - Multicenter Studies as Topic MH - Proportional Hazards Models MH - Prospective Studies MH - *Randomized Controlled Trials as Topic MH - Renal Dialysis/*instrumentation/methods MH - Single-Blind Method PMC - PMC6492371 OTO - NOTNLM OT - Catheter OT - Ethanol OT - Hemodialysis OT - Infection OT - Lock OT - Low molecular weight heparin OT - Tunnelled COIS- 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 Securite du Medicament et des produits de sante (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. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/05/02 06:00 MHDA- 2020/06/06 06:00 PMCR- 2019/04/30 CRDT- 2019/05/02 06:00 PHST- 2018/10/22 00:00 [received] PHST- 2019/04/15 00:00 [accepted] PHST- 2019/05/02 06:00 [entrez] PHST- 2019/05/02 06:00 [pubmed] PHST- 2020/06/06 06:00 [medline] PHST- 2019/04/30 00:00 [pmc-release] AID - 10.1186/s12882-019-1338-6 [pii] AID - 1338 [pii] AID - 10.1186/s12882-019-1338-6 [doi] PST - epublish SO - BMC Nephrol. 2019 Apr 30;20(1):149. doi: 10.1186/s12882-019-1338-6.