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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.

SUBMITTER: Aniort J

PROVIDER: S-EPMC6492371 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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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.

Aniort Julien J Piraud Aurélien A Adda Mireille M Perreira Bruno B Bouiller Marc M Fourcade Jacques J Guerraoui Abdallah A Kalbacher Emilie E Krumel Thierry T Moragues Hélène Leray HL Thibaudin Damien D Vela Carlos Gustavo CG Vernin Guillaume G Weclawiak Hugo H Bernard Lise L Heng Anne Elisabeth AE Souweine Bertrand B

BMC nephrology 20190430 1

<h4>Background</h4>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 prev ...[more]

PMID: 31039759

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Project description:Catheter-related bloodstream infection (CRBSI) results in significant attributable morbidity and mortality. In this randomized, double-blind, placebo-controlled trial, we studied the efficacy and safety of a daily ethanol lock for the prevention of CRBSI in patients with a tunnelled central venous catheter (CVC).From 2005 through 2008, each lumen of the CVC of adult hematology patients was locked for 15 minutes per day with either 70%-ethanol or placebo, where after the lock solution was flushed through. As a primary endpoint, the incidence rates of endoluminal CRBSI were compared.The intent-to-treat analysis was based on 376 patients, accounting for 448 CVCs and 27,745 catheter days. For ethanol locks, the incidence of endoluminal CRBSI per 1000 CVC-days was 0.70 (95%-CI, 0.4-1.3), compared to 1.19 (95% confidence interval, 0.7-1.9) for placebo (incidence rate-ratio, 0.59; 95% confidence interval, 0.27-1.30; P = .19). For endoluminal CRBSI according to the strictest definition (positive hub culture and identical bacterial strain in blood), a 3.6-fold, non-significant, reduction was observed for patients receiving ethanol (2 of 226 versus 7 of 222; P = .103). No life-threatening adverse events were observed. More patients receiving ethanol discontinued lock-therapy (11 of 226 versus 1 of 222; P = .006) or continued with decreased lock-frequency (10 of 226 versus 0 of 222; P = .002), due to non-severe adverse events.In this study, the reduction in the incidence of endoluminal CRBSI using preventive ethanol locks was non-significant, although the low incidence of endoluminal CRBSI precludes definite conclusions. Therefore, the lack of statistical significance may partially reflect a lack of power. Significantly more patients treated with ethanol locks discontinued their prophylactic treatment due to adverse effects, which were non-severe but reasonably ethanol related. Additional studies should be performed in populations with higher incidence of (endoluminal) CRBSI. Alternative sources of bacteremia, like exoluminal CRBSI or microbial translocation during chemotherapy-induced mucositis may have been more important in our patients.ClinicalTrials.gov NCT00122642.

Project description:BackgroundThere is no ideal lock solution that prevents hemodialysis (HD) catheter loss due to catheter-related thrombosis (CRT) and catheter-related bloodstream infection (CRBSI). Catheter loss is associated with increased hospitalization and high inpatient costs. Sodium bicarbonate (NaHCO3) demonstrates anti-infective and anticoagulation properties with a good safety profile, making it an ideal lock solution development target.The objective of this study was to determine the safety and efficacy of using sodium bicarbonate catheter lock solution (SBCLS) as a means of preventing HD catheter loss due to CRT and CRBSI.MethodsThe study took place in a community hospital in Brooklyn, NY, USA. All admitted patients ≥18 years of age who needed HD treatment through CVC were included in the study. 451 patients included in the study were provided SBCLS or NSCLS post-dialysis. Catheter loss due to CRT or CRBSI was evaluated over a period of 546 days.ResultsA total of 452 patients met the criteria; 1 outlier was excluded, 226 were in the NSCLS group and 225 were in the SBCLS group. There were no significant differences between groups in comorbidities at the outset. The NSCLS group had CRT and CRBSI rates of 4.1 and 2.6/1000 catheter days (CD), respectively, compared with 0.17/1000 CD for both outcomes in the SBCLS group. SBCLS patients had a significantly reduced catheter loss rate due to CRT (P < 0.0001) and CRBSI (P = 0.0004). NSCLS patients had higher odds of losing their catheter due to CRT {odds ratio [OR] 26.6 [95% confidence interval (CI) 3.57-198.52]} and CRBSI [OR 15.9 (95% CI 2.09-121.61)] during the study period.ConclusionThe novel approach of using SBCLS was found to be safe and was statistically superior to normal saline in preventing HD catheter loss due to CRT and CRBSI. NaHCO3 solution is inexpensive, readily available in various settings and holds the potential to decrease hospitalization, length of stay and dialysis-related costs.Trial registrationMaimonides Medical Center Investigational Review Board, Study IRB 2015-06-25-CIH. ClinicalTrials.gov identifier: NCT03627884.

Project description:Proper protection of vascular access after haemodialysis is one of the key measures for the prevention of catheter-related infections. Various substances with bactericidal and anticoagulant properties are used to fill catheters, but due to the unsatisfactory clinical effects and occurrence of adverse reactions, the search for new substances is still ongoing. In the present paper, we compared the in vitro antimicrobial activity of solutions used for tunnelled catheter locking (taurolidine, trisodium citrate) and solutions of substances that could potentially be used for this purpose (sodium bicarbonate, polyhexanide-betaine). The studies have been conducted on bacteria that most commonly cause catheter-related infections. The values of both minimum inhibitory concentration and minimum biofilm eradication concentration of the substances were determined. The ability of the tested substances to eradicate biofilm from the dialysis catheter surface was also evaluated. The results showed that polyhexanide-betaine inhibited the growth of all microbes comparably to taurolidine, even after ≥ 32-fold dilution. The activity of trisodium citrate and sodium bicarbonate was significantly lower. Polyhexanide exhibited the highest activity in the eradication of bacterial biofilm on polystyrene plates. The biofilm formed on a polyurethane dialysis catheter was resistant to complete eradication by the test substances. Polyhexanide-betaine and taurolidine showed the highest activity. Inhibition of bacterial growth regardless of species was observed not only at the highest concentration of these compounds but also after dilution 32-128x (taurolidine) and 32-1024x (polyhexanide-betaine). Therefore, it can be assumed that taurolidine application as a locking solution prevents catheter colonization and systemic infection development. Taurolidine displays high antimicrobial efficacy against Gram-positive cocci as well as Gram-negative bacilli. On the contrary, the lowest antibacterial effect displayed product contained sodium bicarbonate. The inhibitions of bacterial growth were not satisfactory to consider it as a substance for colonization prevention. Polyhexanidine-betaine possessed potent inhibitory and biofilm eradication properties comparing to all tested products. PHMB is applied as a wound irrigation solution worldwide. However, based on our results, we assume that the PHMB is a promising substance for catheter locking solutions thanks to its safety and high antimicrobial properties.

Project description:Background and objectivesInterdialytic weight gain in patients on hemodialysis is associated with adverse cardiovascular outcomes and increased mortality. The degree of interdialytic weight gain is influenced by sodium intake. We evaluated the effects of tenapanor (AZD1722 and RDX5791), a minimally systemically available inhibitor of the sodium/hydrogen exchanger isoform 3, on interdialytic weight gain in patients with CKD stage 5D treated with hemodialysis.Design, setting, participants, & measurementsThis phase 2, randomized, double-blind study (NCT01764854; conducted January to September of 2013) enrolled adults on maintenance hemodialysis with interdialytic weight gain ≥3.0% of postdialysis weight and ≥2 kg. Patients were randomly assigned (1:1) to receive tenapanor or placebo. The primary end point was change in mean interdialytic weight gain (percentage of baseline postdialysis weight) from baseline (mean across a 2-week run-in period) to week 4. In a subgroup of inpatients, 24-hour stool sodium and stool weight were assessed for 1 week.ResultsSixteen patients received 1 week of inpatient treatment (tenapanor, eight; placebo, eight), and 72 patients received 4 weeks of treatment in an outpatient setting (tenapanor, 37; placebo, 35; completers: tenapanor, 31; placebo, 33). In the outpatient cohort, no significant effect on interdialytic weight gain was detected; least squares mean changes in relative interdialytic weight gain from baseline to week 4 were tenapanor, -0.26% (95% confidence interval, -0.57% to 0.06%) and placebo, -0.23% (95% confidence interval, -0.54% to 0.07%; P=0.46). During week 1 (inpatient cohort only), compared with placebo, tenapanor treatment resulted in higher stool sodium content (mean [±SD]: tenapanor, 36.6 [±21.8] mmol/d; placebo, 2.8 [±2.7] mmol/d; P<0.001) and higher stool weight (tenapanor, 172.5 [±68.1] g/d; placebo, 86.3 [±30.0] g/d; P<0.01). A similar safety profile was observed across treatment groups with the exception of diarrhea, which occurred more frequently with tenapanor treatment.ConclusionsTenapanor treatment increased stool sodium and weight over placebo in patients undergoing hemodialysis. However, over 4 weeks of treatment, there was no difference in interdialytic weight gain between patients treated with tenapanor and those receiving placebo.

Project description:BACKGROUND AND OBJECTIVES:Interdialytic lock solutions should maintain catheter patency and prevent catheter infections. We aimed to determine in which conditions injectable anticoagulant agents (IAAs) combined with ethanol are compatible and to assess the antibiofilm activity of the selected combination and its effects on dialysis catheters (DC). METHODS:The solubility and compatibility of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), heparinoids and fondaparinux (50 to 2,500 U/mL) in 30 to 70% ethanol were determined by visual observation. The stability of enoxaparin in ethanol and the ethanol content were assessed by high performance liquid chromatography (HPLC) and titrimetric control, respectively. The bactericidal effect was determined on 24h-old biofilms embedded in silicone-DC. The integrity of polyurethane-DC immersed in anticoagulant-ethanol was assessed by gas chromatography-mass spectrometry (GC-MS) and compared with previously published results. RESULTS:The compatibility of IAAs and ethanol varied according to IAA type and concentration, and ethanol content. UFH in 40% ethanol was not compatible, whatever the UFH concentration used. Established limits of compatibility of enoxaparin, nadroparin, dalteparin and tinzaparin in 40% ethanol were 1350, 575, 307 and 207 U/ml, respectively, and up to 300 U/ml for danaparoid and 1 mg/mL for fondaparinux. Enoxaparin 400 U/mL in 40% ethanol (Enox/Eth) eradicated biofilm after 4 hours of exposure for Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans and after 24 hours for Klebsiella pneumoniae and S. aureus. Aliphatic carbonate and alcohol compounds were released by polyurethane-DC after Enox/Eth exposure, as after 40% ethanol or saline exposure. There was no significant difference between the amounts released after 30 minutes of exposure to Enox/Eth and 15 days to saline. CONCLUSIONS:A 40% ethanol solution can be combined with all IAAs but UFH. Enox/Eth was effective as an anti-biofilm agent with minor impacts on DC integrity and could be a useful interdialytic lock solution.

Project description:Hypertension is common in hemodialysis patients; however, the relationship between interdialytic weight gain (IDWG) and blood pressure (BP) is incompletely characterized. This study seeks to define the relationship between IDWG and BP in prevalent hemodialysis subjects.This study used data from 32,295 dialysis sessions in 442 subjects followed up for 6 months in the Crit-Line Intradialytic Monitoring Benefit (CLIMB) Study.Mixed linear regression was used to analyze the relationship between percentage of IDWG (IDWG [%] = [current predialysis weight - previous postdialysis weight]/dry weight * 100) as the independent variable and systolic BP (SBP) and predialysis - postdialysis SBP (deltaSBP) as dependent variables.In unadjusted analyses, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% confidence interval [CI], +/-0.24) increase in predialysis SBP (P < 0.0001), 0.65 mm Hg (95% CI, +/-0.24) decrease in postdialysis SBP (P < 0.0001), and 1.66 mm Hg (95% CI, +/-0.25) increase in deltaSBP (P < 0.0001). After controlling for other significant predictors of SBP, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% CI, +/-0.24) increase in predialysis SBP (P < 0.0001) and a 1.08 mm Hg (95% CI, +/-0.22) increase in deltaSBP with hemodialysis (P < 0.0001). However, in subjects with diabetes as the cause of end-stage renal disease, subjects with lower creatinine levels, and older subjects, the magnitude of the association between percentage of IDWG and predialysis SBP was less pronounced. The magnitude of percentage of IDWG on deltaSBP was less pronounced in younger subjects and subjects with lower dry weights. Results were similar with diastolic BP.Hemodialysis BP measurements are imprecise estimates of BP and true hemodynamic burden in dialysis subjects.In prevalent hemodialysis subjects, increasing percentage of IDWG is associated with increases in predialysis BP and BP changes with hemodialysis; however, the magnitude of the relationship is modest and modified by other clinical factors. Thus, although overall volume status may impact on BP to a greater extent, day-to-day variations in weight gain have a modest role in BP increases in prevalent subjects with end-stage renal disease.

Project description:BACKGROUND:Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. METHODS:In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. RESULTS:Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. CONCLUSIONS:In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

Dataset Information

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.

Publications

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.

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