Prolonged Hemodialysis Catheter Survival With Copolymer Coating and Rt-PA

NCT ID: NCT01670474

Last Updated: 2012-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2012-11-30

Brief Summary

Surface thrombogenicity of standard double lumen catheters (stDLC) and surface modified film-coated domain structured double lumen catheters (fcDLC) consisting of a novel reactive polyurethane copolymer coating showed that in vitro measured surface thrombogenicity was reduced in the modified catheter compared with standard catheter. The clinical investigation revealed that both number of days before catheter removal according to clinical requirements and number of treatments per catheter were significantly higher with the modified catheter as compared with the standard catheter.

Recombinant tissue plasminogen activator (rt-PA) has been used primarily to treat catheter thrombosis. The relatively high cost of rt-PA and its theoretical potential to cause bleeding, as well as the morbidity and mortality associated with catheter malfunction and infection, justify the need for more definitive evidence of the efficacy of rt-PA as a locking solution.

No study aims to evaluate the impact of rt-PA locking in long-term Hemodialysis (HD) uncuffed catheters survival.

Detailed Description

The solution instilled into the central venous catheter lumens after each HD session and left in the catheter until the next session (catheter locking solution) is used to prevent thrombosis during the period between HD sessions and may also prevent catheter-related infection. However, evidence supporting the use of various locking solutions to achieve these objectives is limited. Heparin has been the traditional locking solution. Several small studies have assessed whether citrate and heparin are equally efficacious for maintaining catheter patency but the interpretation of the results was limited because the studies had a short follow-up period and included both uncuffed and cuffed central venous catheters.

Thrombosis is a major cause of HD catheter dysfunction, and this problem is rectified by the use of thrombolytic agents, invasive procedures for declotting, or catheter replacement. A thrombus at the tip of the catheter or a fibrin sheath around it may resist local thrombolysis if it is not reached by sufficient concentrations of the drug. Urokinase has traditionally been used as the thrombolytic agent for HD vascular access declotting, and success rates for declotting vary from 55% to 85%. However, successful treatment of occluded central venous catheter (non HD) with recombinant tissue plasminogen activator (rt-PA) or alteplase was recently achieved in more than 1,000 patients with success (function restored in 798 patients [75.0%; 95% CI: 72.3 to 77.6%]). Serious adverse events monitored within 30 days was very rare and efficacy was independent of age, sex, body weight, and catheter type.

Conditions

Malfunction; Catheter; Thrombosis; Mechanical Complication of Hemodialysis Catheter

Keywords

Temporary hemodialysis catheters; Non-cuffed hemodialysis catheters; Thrombolysis; rt-PA; Thrombosis; Lifespan; Blood flow rate; Catheter related bacteriemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

fmDLC and rt-PA (2mg/2mL actilysis)

Surface thrombogenicity of film-coated domain structured double lumen catheters (fmDLC) consisting of a novel reactive polyurethane copolymer coating will be assessed by measurement of thrombin-antithrombin (TAT) III complex in vitro after the use of rt-PA (2mg/2mL) in each lumen of the catheter for 45 minutes.

Each lumen of the thrombosed (dysfunctional) catheter will be locked with the exact volume (luminal volume) of rt-PA (rt-PA (2mg/2mL) actilysis) during 45 min.

Group Type: EXPERIMENTAL

rt-PA (2mg/2mL) actilysis

Intervention Type: DRUG

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. All catheters analyzed (fmDLC, polyDLC and siDLC) will be locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions: i.e. fmDLC, polyDLC amd siDLC.

rt-PA

Intervention Type: DRUG

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed in this study (i.e. fmDLC, polyDLC, siDLC) will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions.

polyDLC and rt-PA (2mg/2mL actilysis)

The same procedure will be assessed in the polyurethane double lumen catheter (polyDLC)as with the fmDLC. Indeed, surface thrombogenicity of polyDLC will be assessed by measurement of thrombin-antithrombin (TAT) III complex in vitro after the use of rt-PA (2mg/2mL) in each lumen of the catheter for 45 minutes.

Each lumen of the thrombosed (dysfunctional) catheter will be locked with the exact volume (luminal volume) of rt-PA (rt-PA (2mg/2mL) actilysis) during 45 min.

Group Type: ACTIVE_COMPARATOR

rt-PA (2mg/2mL) actilysis

Intervention Type: DRUG

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. All catheters analyzed (fmDLC, polyDLC and siDLC) will be locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions: i.e. fmDLC, polyDLC amd siDLC.

rt-PA

Intervention Type: DRUG

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed in this study (i.e. fmDLC, polyDLC, siDLC) will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions.

siDLC and rt-PA (2mg/2mL actilysis)

Same procedure as the previous catheters. Surface thrombogenicity of silicone double lumen catheter (siDLC) will be assessed by measurement of thrombin-antithrombin (TAT) III complex in vitro after the use of rt-PA (2mg/2mL) in each lumen of the catheter for 45 minutes.

Each lumen of the thrombosed (dysfunctional) catheter will be locked with the exact volume (luminal volume) of rt-PA (rt-PA (2mg/2mL) actilysis) during 45 min.

Group Type: ACTIVE_COMPARATOR

rt-PA (2mg/2mL) actilysis

Intervention Type: DRUG

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. All catheters analyzed (fmDLC, polyDLC and siDLC) will be locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions: i.e. fmDLC, polyDLC amd siDLC.

rt-PA

Intervention Type: DRUG

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed in this study (i.e. fmDLC, polyDLC, siDLC) will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions.

Interventions

rt-PA (2mg/2mL) actilysis

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. All catheters analyzed (fmDLC, polyDLC and siDLC) will be locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions: i.e. fmDLC, polyDLC amd siDLC.

Intervention Type: DRUG

rt-PA

At the first catheter dysfunction (Qb \< 250 ml/min) due to thrombotic event, the patient will receive rt-PA (2mg/2mL Alteplase vial - Cathflo, Boehringer Ingelheim, Ingelheim, Germany). Each lumen of the thrombosed catheter is locked with the exact volume (luminal volume) of rt-PA during 45 min. Each catheter analyzed in this study (i.e. fmDLC, polyDLC, siDLC) will be filled with rt-PA (2mg/2mL) if they are dysfunctional as described above in Arm/Group Descriptions.

Intervention Type: DRUG

Other Intervention Names

Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany; Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany)

Eligibility Criteria

Inclusion Criteria

• End-stage kidney disease patients with newly inserted temporary untunnelled dual-lumen catheter
• Naive to study but not naive to catheters (both virgin and non-virgin catheters will be included)
• Expected to use catheter, and to dialyze at study centre, for at least six months
• Frequency of HD 3 times per week
• If indication for catheter was replacement for catheter related infection patients will be eligible after the infection has been treated and the patient has been off antibiotics for 3 HD sessions
• Patient or legal representative able to provide written consent
• Eighteen years of age or older
• Baseline INR ≤ 1.3 (no anticoagulation allowed outside the HD session)
• Baseline platelet count ≥ 60 x 109/L

• Major haemorrhage in the prior 4 weeks, defined as bleeding resulting in a drop in haemoglobin of greater than 20 g/L or bleeding requiring transfusion of packed red blood cells with other clinical evidence or suspicion of bleeding
• History of intra-cranial bleed in the prior 4 weeks
• Intra-cranial or intra-spinal neoplasm (current)
• Allergy or intolerance to rt-PA or heparin or its constituents
• Active pericarditis - defined by the presence of a pericardial rub
• Weight ≤ 30 kg or > 130 kg
• Patient pregnant or lactating
• Child bearing potential (i.e. pre-menopausal woman who is not using a reliable method of contraception)
• Major surgery in past 48 hours (CABG, organ biopsy, puncture of non-compressible vessels), or scheduled for major surgery during the study period
• Involvement in another randomized drug trial
• Presence of a fever as defined by a temperature > 38.2°C

Exclusion Criteria

• Use of systemic anticoagulation (if indication for anticoagulation is catheter patency patients may be eligible if the systemic anticoagulation is discontinued and baseline INR is ≤ 1.3)
• Insertion of a new catheter into the femoral vein

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier du Centre du Valais

OTHER

Sponsor Role: lead

Responsible Party

Pascal Meier MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pascal Meier, MD

Role: PRINCIPAL_INVESTIGATOR

CHCVs - RSV - Hôpital du Valais

Locations

Centre Hospitalier du Centre du Valais (CHCVs)

Sion, Valais, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Pascal Meier, MD

Role: CONTACT

Phone: +41276038647

Email: pascal.meier@hopitalvs.ch

Facility Contacts

Pascal Meier, MD

Role: primary

References

Meier P, Meier R, Turini P, Friolet R, Blanc E. Prolonged catheter survival in patients with acute kidney injury on continuous renal replacement therapy using a less thrombogenic micropatterned polymer modification. Nephrol Dial Transplant. 2011 Feb;26(2):628-35. doi: 10.1093/ndt/gfq449. Epub 2010 Jul 28.

Reference Type: RESULT

PMID: 20667989 (View on PubMed)

Other Identifiers

Cath-a-lysis

Identifier Type: REGISTRY

Identifier Source: secondary_id

PROCOPrt-PA

Identifier Type: -

Identifier Source: org_study_id