Study Assessing Safety & Effectiveness of a Catheter Lock Solution in Dialysis Patients to Prevent Bloodstream Infection

Phase 3 Prospective, Multicenter, Double-blind, Randomized, Active Control Study to Demonstrate Safety & Effectiveness of Neutrolin in Preventing Catheter-related Bloodstream Infection in Subjects on Hemodialysis for End Stage Renal Disease

The purpose of this study is determine safety and effectiveness of Neutrolin, a catheter lock solution, for prevention of central venous catheter associated bloodstream infection in hemodialysis patients.

The objective of this study is to demonstrate the efficacy and safety of Neutrolin® as a catheter lock solution (CLS) on prevention of catheter-related bloodstream infection (CRBSI), and the incidence of treatment-emergent adverse events in subjects receiving hemodialysis (HD) for the treatment of End Stage Renal Disease (ESRD) when compared with heparin 4,000 USP Units/4mL (1,000 USP Units/mL).

This is a randomized, double-blind, active control, parallel-arm, multicenter study. Six hundred and thirty two subjects will be randomized in a 1:1 ratio to receive either Neutrolin® or the active control heparin (Heparin sodium USP 1,000 units/mL, Benzyl alcohol 9.45 mg/mL and Sodium chloride 9.0 mg/mL) as a CLS.

Approximately 632 randomized subjects are planned for this trial. In this study, one-half of the subjects (316 subjects) will receive Neutrolin as a study drug and the other half will receive heparin 4,000 USP Units/4mL (1,000 USP Units/mL) with benzyl alcohol preservative as a comparator. Subjects will be assigned in a 1:1 ratio using permuted blocks without additional stratification for both groups.

The primary objective of this study is to demonstrate the effectiveness of Neutrolin® as a CLS in ESRD subjects undergoing HD treatment using a permanent, cuffed, tunneled silicone or polyurethane HD catheter. The study will evaluate whether Neutrolin® is superior to the active control heparin by documenting the time to CRBSI and consequently delaying the time until the occurrence of CRBSI.

Inclusion Criteria:

1. Subject has ESRD and undergoes chronic HD at least two times per week
2. Subject has a HD catheter that has demonstrated the ability to achieve a minimum blood flow of at least 250 mL/min for at least two consecutive dialysis sessions blood flow to enable successful HD
3. The HD catheter is implanted with the tip in a jugular or subclavian vein
4. The subject is not expected to expire within 180 days
5. The subject is likely to require the use of a CVC for at least 90 days
6. The subject (or the legal guardian) understands the nature of the study and provides written informed consent prior to the study enrollment
7. The subject is willing to comply with specified follow-up evaluations and prescribed dialysis therapy and
8. If female and of childbearing potential, the subject must have a negative pregnancy test at the screening visit (i.e., subject is not pregnant); not be lactating; and use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or hormonal contraceptive (oral, implant, ring, patch) for the duration of the study. (NOTE: The subject must have used the chosen method of birth control for at least 1 month/cycle prior to enrollment into the study).

Exclusion Criteria:

1. Subjects who received antibiotics within the last 14 days

2. Visible evidence of compromised skin integrity is present at the catheter exit site or evidence of a catheter exit site infection

3. Subject has received any thrombolytic treatment (i.e., tPA) in their current catheter within 30 days of randomization

4. Fill volume of HD catheter is unknown or cannot be determined

5. Subjects using any type of antimicrobial-coated or heparin-coated catheter

6. Documented chronic bleeding diathesis, active or recurrent bleeding within 1 month prior to randomization

7. Documented history of an atrial thrombus or known hypercoagulable state

8. Subjects with open, non-healing skin ulcers

9. Current requirement for systemic immunosuppression that would increase risk of infection

10. Active malignancy requiring or anticipated to require chemotherapy likely to cause leukopenia and/or immunosuppression

11. Known allergy or absolute contraindication to citrate, taurolidine or heparin or a history of heparin-induced thrombocytopenia

12. Unstable malignancy

13. Cirrhosis with encephalopathy

14. Subject is currently taking another medication with known systemic drug interaction with citrate, taurolidine, or heparin

15. Subject is currently enrolled in another investigational device and/or drug trial or has participated in another investigational device and/or drug trial within 30 days prior to enrollment

16. Subject is anticipated to receive a renal transplant within 90 days (subjects can be on the transplant list, but a subject with a known or anticipated transplant date within the next 90 days should be excluded)

17. Any other medical condition which renders the subject unable to or unlikely to complete the study, or which would interfere with optimal participation in the study or produce significant risk to the subject.

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