Taurolidine/Heparin Lock Solution and Catheter-Related Bloodstream Infection in Hemodialysis: A Randomized, Double-Blind, Active-Control, Phase 3 Study.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are one of the most prevalent, fatal, and costly complications of hemodialysis with a central venous catheter (CVC). The LOCK IT-100 trial compared the efficacy and safety of a taurolidine/heparin catheter lock solution that combines taurolidine 13.5 mg/ml and heparin (1000 units/ml) versus heparin in preventing CRBSIs in participants receiving hemodialysis via CVC. METHODS: LOCK IT-100 was a randomized, double-blind, active-control, multicenter, phase 3 study that enrolled adults with kidney failure undergoing maintenance hemodialysis via CVC from 70 US sites. Participants were randomized 1:1 to taurolidine/heparin catheter lock solution or heparin control catheter lock solution (1000 units/ml). The primary end point was time to CRBSI as assessed by a blinded Clinical Adjudication Committee. Secondary end points were catheter removal for any reason and loss of catheter patency. On the basis of a prespecified interim analysis, the Data and Safety Monitoring Board recommended terminating the trial early for efficacy with no safety concerns. RESULTS: In the full analysis population ( N =795), nine participants in the taurolidine/heparin arm ( n =397; 2%) and 32 participants in the heparin arm ( n =398; 8%) had a CRBSI. Event rates per 1000 catheter days were 0.13 and 0.46, respectively, with the difference in time to CRBSI being statistically significant, favoring taurolidine/heparin ( P < 0.001). The hazard ratio was 0.29 (95% confidence interval, 0.14 to 0.62), corresponding to a 71% reduction in risk of CRBSIs with taurolidine/heparin versus heparin. There were no significant differences between study arms in time to catheter removal for any reason or loss of catheter patency. The safety of taurolidine/heparin was comparable with that of heparin, and most treatment-emergent adverse events were mild or moderate. CONCLUSIONS: Taurolidine/heparin reduced the risk of developing a CRBSI in study participants receiving hemodialysis via CVC compared with heparin with a comparable safety profile. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Study Assessing Safety & Effectiveness of a Catheter Lock Solution in Dialysis Patients to Prevent Bloodstream Infection, NCT02651428 .

Agalsidase beta treatment slows estimated glomerular filtration rate loss in classic Fabry disease patients: results from an individual patient data meta-analysis.

BACKGROUND: Fabry disease is a rare, X-linked genetic disorder that, if untreated in patients with the Classic phenotype, often progresses to end-stage kidney disease. This meta-analysis determined the effect of agalsidase beta on loss of estimated glomerular filtration rate (eGFR) in the Classic phenotype using an expansive evidence base of individual patient-level data. METHODS: The evidence base included four Sanofi-Genzyme studies and six studies from a systematic literature review. These were restricted to Classic Fabry patients meeting the eligibility criteria from Phases III and IV agalsidase beta trials, including 315 patients (161 treated). Linear regression was first used to model annual change in eGFR for each patient and the resulting annualized eGFR slopes were modelled with treatment and covariates using quantile regression. These results were then used to estimate median annualized eGFR change in agalsidase beta treated versus untreated groups. RESULTS: Imbalances across treatment groups were found in baseline age, sex and proteinuria, but not in the use of renin-angiotensin system blockers. The adjusted model suggests that treated (agalsidase beta) patients experienced a slower median eGFR decrease [2.46 mL/min/1.73 m2/year slower; 95% confidence interval (CI) 0.63-4.29; P = 0.0087] than comparable untreated patients. The median eGFR decrease was 2.64 mL/min/1.73 m2/year slower (95% CI 0.53-4.78; P = 0.0141) in treated Classic males. CONCLUSIONS: Using an expansive evidence base and robust modelling approach, these data indicate that agalsidase beta-treated patients with the Classic phenotype conserve their renal function better than untreated patients.