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Clinical Trial
. 2023 Nov 1;18(11):1446-1455.
doi: 10.2215/CJN.0000000000000278. Epub 2023 Sep 6.

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

Anil K Agarwal  1 , Prabir Roy-Chaudhury  2   3 , Phoebe Mounts  4 , Elizabeth Hurlburt  4 , Antony Pfaffle  4 , Eugene C Poggio  5
Affiliations
Clinical Trial

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

Anil K Agarwal et al. Clin J Am Soc Nephrol. .

Abstract

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 .

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Conflict of interest statement

A.K. Agarwal reports employment with VA Central California Health Care System; consultancy for Akebia; honoraria from Amgen; advisory or leadership roles for ASDIN, Clinical Nephrology, Frontiers in Nephrology, International Journal of Nephrology, ISN, Journal of Vascular Access, KSAP, NKF, and The Open Urology & Nephrology Journal (all unpaid); advisor role to AstraZeneca and Otsuka; research support from Akebia Pharmaceuticals; and other interests or relationships with ASDIN, ASN, ISN, and NKF. E. Hurlburt reports employment with CorMedix, Inc. P. Mounts reports employment with, ownership interest in, and advisory or leadership role for CorMedix Inc. A. Pfaffle reports employment with, ownership interest in, and advisory or leadership roles for CorMedix Inc. A. Pfaffle has served as the Chief Scientific Officer and Head of Patient Advocacy and Special Projects at CorMedix. E.C. Poggio is the founder and owner of Biostatistical Consulting Inc. (BCI), which provided statistical design and analysis services to CorMedix Inc. BCI provides biostatistical consulting to numerous pharmaceutical, biotech, and medical device companies for which it is paid. E.C. Poggio reports ownership interest in AstraZeneca, Acurx, and Biostatistical Consulting Inc. E.C. Poggio's wife reports employment with AstraZeneca. P. Roy-Chaudhury reports employment with VAMC Salisbury, NC; consultancy for Akebia, Alexion (AstraZeneca Rare Diseases), AstraZeneca, Bayer, Becton Dickinson, CorMedix, Humacyte, Medtronic, Target RWE, and WL Gore; ownership interest as Chief Scientific Officer and Founder of Inovasc LLC; NIH Small Business Grants as MPI or site PI with Adgero, Cylerus, Eko, and Inovasc; honoraria from Akebia, Alexion (AstraZeneca Rare Diseases), AstraZeneca, Bayer, Becton Dickinson, Cormedix, Humacyte, Medtronic, N9, and WL Gore; research funding from Bayer; and advisory or leadership roles for Akebia, Alexion (AstraZeneca Rare Diseases), ASN, AstraZeneca, Bayer, Becton Dickinson, BioMed Innovations, Cormedix, Editorial Board of Journal of Vascular Access, Humacyte, Medtronic, N9, Vascular Access Society of the Americas, and WL Gore.

Figures

None
Graphical abstract
Figure 1
Figure 1
Study flow diagram. aTwo participants with laboratory values at screening not meeting eligibility criteria were mistakenly dosed without being randomized (one in each study arm) and were subsequently withdrawn. These two participants were included in the safety population but not the full analysis population.
Figure 2
Figure 2
Kaplan–Meier survival curve for time to CRBSI through 24 months (primary outcome, full analysis population). CRBSI, catheter‐related bloodstream infection.
Figure 3
Figure 3
HR (95% CI) of incidence of CRBSI by subgroups (primary outcome, full analysis population). CI, confidence interval; CVC, central venous catheter; HR, hazard ratio.
See this image and copyright information in PMC

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