Taurolidine and Heparin Lock Product Lowers CRBSI Risk

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A newly approved taurolidine and heparin lock solution reduces the risk of catheter-related bloodstream infection (CRBSI) in patients undergoing hemodialysis with a central venous catheter (CVC), as demonstrated by a pivotal trial in CJASN.

The phase 3 “LOCK-IT-100” (Study Assessing Safety & Effectiveness of a Catheter Lock Solution in Dialysis Patients to Prevent Bloodstream Infection) trial included 795 adults receiving maintenance hemodialysis with a permanent CVC enrolled at 70 US centers. Patients were randomly assigned to receive a taurolidine (13.5 mg/mL) and heparin (1000 U/mL) solution or heparin only. Study solutions were instilled at the end of each hemodialysis session. Baseline characteristics were similar between groups. The primary outcome was the occurrence of CRBSI, assessed by blinded clinical adjudication. Catheter removal and loss of patency were evaluated as secondary outcomes.

Of 41 CRBSI events, 32 occurred in the heparin-only group: 2% of patients assigned to taurolidine and heparin versus 8% with heparin only. Event rates were 0.3 for heparin only versus 0.46 for taurolidine and heparin per 1000 catheter days. The hazard ratio for CRBSI was 0.28 in the taurolidine and heparin group. Based on this “highly statistically significant” result and the absence of safety issues, the study was terminated after a planned interim analysis.

Secondary outcomes were similar between groups. Most patients in both groups experienced treatment-emergent adverse events, mainly mild to moderate. In both groups, 5% of patients died, most commonly due to cardiac causes.

The LOCK-IT-100 results led to US Food and Drug Administration (FDA) approval of the proprietary taurolidine and heparin catheter lock solution, marketed as DefenCath. It is the third drug to be approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs and received both a fast-track and Qualified Infectious Disease Product designation, according to an FDA announcement.

By lowering the risk of CRBSIs, the new product is likely to reduce morbidity and mortality in the vulnerable group of in patients undergoing hemodialysis with CVCs. The investigators conclude: “Reducing CRBSIs in hemodialysis patients will likely increase the efficiency of care and reduce the number and duration of hospitalizations and overall costs” [Agarwal AK, et al. Taurolidine/heparin lock solution and catheter-related bloodstream infection in hemodialysis: A randomized, double-blind, active-control, phase 3 study. Clin J Am Soc Nephrol 2023; 18:1446–1455. doi: 10.2215/CJN.0000000000000278].