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 .

Regulatory strategies to facilitate surgical innovation.

Phoebe Mounts, PhD, Esq, is a partner in the Food and Drug Administration Practice Group in the Washington, DC, office of Morgan Lewis & Bockius LLP. She counsels clients on regulatory issues for medical devices, drugs, and biologics. Prior to joining Morgan Lewis, she was on the faculty of the Johns Hopkins University School of Public Health in the Department of Molecular Microbiology, Immunology, and Infectious Diseases. Although she is a partner in the FDA Practice Group at Morgan Lewis, the views expressed in this article are hers and should not be attributed to the Firm.