Alteplase for Blood Flow Restoration in Hemodialysis Catheters

Alteplase for Blood Flow Restoration in Hemodialysis Catheters: A Randomized Prospective Clinical Trial

We are investigating a new way of administering alteplase to remove clots from hemodialysis catheters. Currently, alteplase is left to dwell inside the catheter between dialysis treatments to dissolve the clot and restore blood flow through the catheter. We have developed a new way to administer alteplase by advancing it to the tip of the catheter at regular 10 minute intervals. We hypothesize that our new "push" protocol will dissolve clots in hemodialysis catheters better and faster than the current dwell method.

Study Overview

• Status: Terminated
• Conditions: Thrombosis
• Intervention / Treatment: Drug: alteplase dwell arm; Drug: Alteplase "push" protocol

Detailed Description

Central venous catheters are commonly used for vascular access in the hemodialysis population. A common complication is low / no blood flow through the catheter due to clots. These are serious situations because patients may miss dialysis sessions and suffer significant morbidity. In an attempt to dissolve the clots and restore blood flow, thrombolytics are frequently instilled into the catheters between dialysis sessions . However, we have developed and new "push" protocol that advances fresh thrombolytic (alteplase) to the tip of the catheter in order to facilitate more effective and faster removal of the clot. We hypothesize that our new "push" protocol will dissolve clots in hemodialysis catheters better and faster than the current dwell method.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Brandon, Manitoba, Canada, R7A 2B3
      • Brandon General Hospital
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface Hospital
    • Winnipeg, Manitoba, Canada, R2V 3M3
      • Seven Oaks Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y3
      • St. Joseph's Hospital
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Hospital
    • Thunderbay, Ontario, Canada, P7B 6V4
      • Thunderbay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve Rosemont Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults > 18 yrs old
2. Hemodialysis patients
3. Vascular access with a permanent catheter
4. No prior rt-PA use in the catheter over the previous 21 days
5. One rt-PA instillation per catheter (i.e. we will only document the results of 1 rt-PA instillation per catheter. Numerous rt-PA instillations in the same catheter will NOT be considered new events, and not entered into the study)

Exclusion Criteria:

1. Critically ill patients in the ICU setting.
2. Contraindications / cautions with alteplase use including: known hypersensitivity to alteplase or its components (l-arginine, phosphoric acid, polysorbate 80), patients with known conditions associated with bleeding events (e.g.intracranial bleed in last 4 weeks, major hemorrhage in last 4 weeks (Hgb drop of 20 g/L)), recent surgery (<48 hours), recent biopsy (<48 hours), hemostatic defects including severe hepatic disease, or current intracranial / intraspinal neoplasm.
3. Hemodialysis catheter has been in the patient less than 14 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Alteplase used by normal dwell procedure	Drug: alteplase dwell arm; alteplase 2 mg / lumen. Instill and let it dwell for 30 minutes. Assess catheter and allow to dwell for a total of 2 hours if necessary; Other Names: alteplase; rTPA; Cathflo
Experimental: 2; Alteplase given by an new "push" protocol	Drug: Alteplase "push" protocol; alteplase 2 mg / lumen. Instill and wait 10 minutes, instill 0.3 ml normal saline, wait 10 minutes, instill 0.3 ml of normal saline, wait 10 minutes and aspirate.; Other Names: CathFlo; alteplase; rTPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with pre-thrombolytic blood flows less than 200 ml/min achieving a "sustainable" post thrombolytic blood flow > or = 300 ml/min.	4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Highest recorded "sustainable" blood flow (ml/min) pre- and post- thrombolytic administration.	4 hours
Change in Kt/V from the treatment before thrombolytic administration compared to the treatment after thrombolytic administration.	72 hours
Change in "litres processed / time" from the treatment before thrombolytic administration compared to the treatment after thrombolytic administration.	72 hours
Serious adverse events including major bleeding within 24 hours of alteplase administration	30 days post-last dose

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Lavern M Vercaigne, Pharm.D., University of Manitoba; Principal Investigator: James M Zacharias, MD, University of Manitoba, Internal Medicine, Section of Nephrology

Publications and helpful links

General Publications

• Zacharias JM, Weatherston CP, Spewak CR, Vercaigne LM. Alteplase versus urokinase for occluded hemodialysis catheters. Ann Pharmacother. 2003 Jan;37(1):27-33. doi: 10.1345/aph.1C105.

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: March 15, 2006
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (Estimate): March 16, 2006

Study Record Updates

• Last Update Posted (Estimate): December 19, 2008
• Last Update Submitted That Met QC Criteria: December 17, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: hemodialysis; alteplase; dysfunction; thrombolytic; catheter
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: B2003:119