Comparison of Effectiveness and Safety of Three Lock Solutions for Long-Term Central Venous Catheter for Hemodialysis (CLOCK)

Background: Poor flow (PF) and catheter-related blood stream infections (CRBSI) are highly prevalent among CKD 5D patients with long-term central venous catheters. Heparin (H) catheter lock solutions are commonly used to maintain catheter patency, however PF and CRBSI incidence remains high. The purpose of this study was to evaluate two lock solutions on reduction of PF and CRBSI: one, a lock solution combining of the tetracycline antibiotic minocycline with the anticoagulant/chelation agent EDTA (M-EDTA) versus H; and other, trisodium citrate (C) versus H. M-EDTA and C were also evaluated as to their safety versus H.

Methods:As regards the pilot project, thirty CKD 5D patients on high-efficiency hemodialysis (blood flow rate = 350 ml/min) at the Integrated Centre of Nephrology (Guarulhos, Brazil) were randomized 1:1:1 to receive M-EDTA, C or H locks for 15 weeks. Lock solutions concentrations were M-EDTA 30 mg/ml/3 mg/ml, C 30% (C) and H 1,000 U/ml and both investigators and patients were blinded to treatment allocation. The primary end-point was a 10% reduction in HD blood flow rates (35ml). The frequency of CRBSI was recorded. Bleeding and lock solution-related adverse events were the primary safety end points. Logistic Regression was performed to evaluate differences in PF rates among the treatments (SPSS version 13.0, IBM, USA).

Based upon the pilot-study data, the clinical trials has being executed in order to verify whether the three lock solutions have the same performance or not.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Heparin Lock Solution; Drug: Trissodium Citrate 30%; Drug: Minocycline-EDTA 30 mg/ml - 3 mg/ml

Detailed Description

Methods: 75 CKD 5D patients on high-efficiency hemodialysis (blood flow rate = 350 ml/min) at the Integrated Centre of Nephrology (Guarulhos, Brazil) will be randomized 1:1:1 to receive M-EDTA, C or H locks for 15 weeks. Lock solutions concentrations are M-EDTA 30 mg/ml/3 mg/ml, C 30% (C) and H 1,000 U/ml and both investigators and patients are blinded to treatment allocation. The primary end-point is a 10% reduction in HD blood flow rates (35ml). The frequency of CRBSI will be recorded. Poor Flow Rate (event/1,000 catheter-day) and CRBSI Rate (event/1,000 catheter-day) will be calculated in each arm. Bleeding and lock solution-related adverse events are also the primary safety end points and their rates (events/1,000 catheter-day) will be calculated. Logistic Regression will be performed to evaluate differences in PF, CRBSI, Bleeding and lock solution-related adverse events rates among the treatments (SPSS version 13.0, IBM, USA).

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Guarulhos, Sao Paulo, Brazil, 07013-142
      • Integrated Centre of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male and female patients;
• patients with subclavian long term central venous catheter;
• patients on on high-efficiency hemodialysis (BFR= 350 ml; dialisate flow = 500 ml; 3 times; 4-hour sessions).

Exclusion Criteria:

• pregnant; patients on oral coagulants; patients aged less than 18 years;
• patients aged more than 75 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Heparin Lock Solution; Patients on Heparin 1,000 U/ml locking solution, administered at the end of each dialysis session during a 15-week period .	Drug: Heparin Lock Solution; Just after the insertion (since first the hemodialysis session), long-term Central Venous Catheter of CKD 5D patients on high-efficiency hemodialysis have been locked during 15 weeks (100 days) with appropriate lock solution.; Other Names: Hemofol (Traade Mark)
Experimental: Trissodium Citrate 30%; Patients on trissodium citrate 30% locking solution, administered at the end of each dialysis session during a 15-week period .	Drug: Trissodium Citrate 30%; ust after the insertion (since first the hemodialysis session), long-term Central Venous Catheter of CKD 5D patients on high-efficiency hemodialysis have been locked during 15 weeks (100 days) with appropriate lock solution.; Other Names: CitraLock(Trade Mark)
Experimental: Minocycline-EDTA 30 mg/ml - 3 mg/ml; Patients on Minocycline 30 mg/ml/EDTA 3 mg/ml locking solution, administered at the end of each dialysis session during a 15-week period.	Drug: Minocycline-EDTA 30 mg/ml - 3 mg/ml; ust after the insertion (since first the hemodialysis session), long-term Central Venous Catheter of CKD 5D patients on high-efficiency hemodialysis have been locked during 15 weeks (100 days) with appropriate lock solution.; Other Names: Cath-Safe (Trade Mark)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Poor Blood Flow Rate(BFR)	Reduction of 35 ml in the BFR of 2350 ml on hemodialysis is considered a primary endpoint for this trial	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Drug Reactions Related to lock solutions (ADR)	ADR is considered secondary endpoint for this trial	100 days
Cather-Related Blood Stream Infection (CRBSI)	CRBSI is considered secondary endpoint for this trials	100 days

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Marcus Luiz, MSc, PharmD, PhD student

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 18, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): December 1, 2015

Study Record Updates

• Last Update Posted (Estimate): December 2, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: renal dialysis
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Anti-Bacterial Agents; Anticoagulants; Heparin; Minocycline
• Other Study ID Numbers: USaoPaulo CLOCK