Prolonged Hemodialysis Catheter Survival With Copolymer Coating and Rt-PA (PROCOPrt-PA)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by Centre Hospitalier du Centre du Valais.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Pascal Meier MD, Centre Hospitalier du Centre du Valais
ClinicalTrials.gov Identifier:
NCT01670474
First received: March 20, 2012
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Malfunction; Catheter
Thrombosis
Mechanical Complication of Hemodialysis Catheter
Drug: rt-PA (2mg/2mL) actilysis
Drug: rt-PA
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Prolonged Hemodialysis Catheter Survival With Copolymer Coating and Rt-PA - PROCOPrt-PA Trial

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier du Centre du Valais:

Primary Outcome Measures:
  • Lifespan patency with the ability to complete HD session in three different UCs using rt-PA locking protocol [ Time Frame: 240 days after patients' enrollement ] [ Designated as safety issue: Yes ]
    The ability to achieve blood flow rates of >= 250 mL/min in three different UCs using rt-PA locking protocol if the UCs present a clotting event (complete or partial thrombosis).


Secondary Outcome Measures:
  • The incidence of catheter-related bacteremia after rt-PA use in case of thrombosed UCs [ Time Frame: 240 days after patients' enrollement ] [ Designated as safety issue: Yes ]
    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.

  • Economic evaluation of rt-PA in catheter patency after UCs dysfunction [ Time Frame: 240 days after patients' enrollement ] [ Designated as safety issue: Yes ]
    An economic evaluation of rt-PA in catheter patency after dysfunction (partial or complete catheter thrombosis) will be conducted.


Other Outcome Measures:
  • Number of patients who complete HD session with short term HD catheters using rt-PA. [ Time Frame: 240 days after patients' enrollement ] [ Designated as safety issue: Yes ]
    This analysis aims to see if rt-PA will decrease the incidence of catheter malfunction due to thrombosis in three different UCs of different synthetic material.


Estimated Enrollment: 240
Study Start Date: January 2011
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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.
Other Name: Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany
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.
Other Name: Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany)
Active Comparator: 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.

Drug: 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.
Other Name: Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany
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.
Other Name: Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany)
Active Comparator: 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.

Drug: 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.
Other Name: Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany
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.
Other Name: Cathflo, 2mg/2mL (Boehringer Ingelheim, Ingelheim/Germany)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  • Current use of antibiotics for catheter-related bacteraemia (see inclusion criteria above)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670474

Contacts
Contact: Pascal Meier, MD +41276038647 pascal.meier@hopitalvs.ch

Locations
Switzerland
Centre Hospitalier du Centre du Valais (CHCVs) Recruiting
Sion, Valais, Switzerland, 1950
Contact: Pascal Meier, MD    +41276038647    pascal.meier@hopitalvs.ch   
Sub-Investigator: Rachel Meier, SN         
Sponsors and Collaborators
Centre Hospitalier du Centre du Valais
Investigators
Principal Investigator: Pascal Meier, MD CHCVs - RSV - Hôpital du Valais
  More Information

Publications:
Responsible Party: Pascal Meier MD, Professor, Centre Hospitalier du Centre du Valais
ClinicalTrials.gov Identifier: NCT01670474     History of Changes
Other Study ID Numbers: PROCOPrt-PA, Cath-a-lysis
Study First Received: March 20, 2012
Last Updated: August 20, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Centre Hospitalier du Centre du Valais:
Temporary hemodialysis catheters
Non-cuffed hemodialysis catheters
Thrombolysis
rt-PA
Thrombosis
Lifespan
Blood flow rate
Catheter related bacteriemia

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on September 22, 2014