A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters

NCT00396253 | Completed Phase 3 Results

• 1 other identifier: N3701g
• Study Type: interventional
• Target: 223
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a Phase III, open-label study conducted at 44 centers in the United States, Canada, and Puerto Rico. 223 subjects who required hemodialysis (HD) and had a dysfunctional HD catheter were enrolled in the study.

Conditions

Dysfunctional Hemodialysis Catheters

Keywords

HD; TNKase; Hemodialysis; Catheter clearance

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1

  Treatment success is defined as Blood Flow Rate (BFR) ≥ 300 mL/min and an increase of ≥ 25 mL/min from baseline BFR (without reversal of lines), at an associated arterial pressure in the range of 0 to -280 mmHg, 30 (± 10) minutes prior to the end of hemodialysis and at the end of hemodialysis.

  Visit 1 (the first hemodialysis session in which treatment was administered). BFR was measured at the beginning of hemodialysis (Baseline measurement) and at 30 minutes prior to the end of hemodialysis and at the end of hemodialysis.

• Targeted Adverse Events From the Initial Study Drug Administration Through the Start of Visit 2 or Until Instillation of Extended-Dwell Tenecteplase

  The primary outcome measure was the number of targeted adverse events, occurring from initial study drug administration through the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for subjects who did not receive open-label, extended-dwell tenecteplase, from initial study administration through the start of Visit 2. Targeted adverse events were defined as intracranial hemorrhage, major bleeding and embolic events, thrombosis, Catheter-related blood stream infection (CRBSIs), and catheter-related complications.

  From initial study drug administration to the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for patients who did not receive extended-dwell tenecteplase, from initial study administration to the start of Visit 2.

Secondary Outcomes (7)

• Percentage of Participants Who Maintained Catheter Function at Visits 2 and 3

  Maintenance BFR measurements were taken at the beginning of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1) and Visit 3 (3rd consecutive HD session, within 72 hours of Visit 2).

• Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 1

  At Visit 1 (first hemodialysis session in which treatment was administered) samples for blood urea nitrogen measurements were taken at the beginning of HD (prior to treatment administration) and after HD was completed.

• Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 2

  At Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1) samples for blood urea nitrogen measurements were taken prior to HD and after HD was completed.

• Change in Blood Flow Rate From Baseline to the End of Hemodialysis at Visit 1

  Baseline (beginning of HD at Visit 1) to the end of HD at Visit 1.

• Percentage of Participants Who Failed Treatment at Visit 1 With Treatment Success at Visit 2

  BFR was measured 30 minutes before the end of HD and at the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1). Baseline BFR was measured at the beginning of HD at Visit 1.

Study Arms (1)

Tenecteplase

EXPERIMENTAL

At each treatment, subjects had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Subjects could receive up to three treatments with tenecteplase, the first two as part of the initial treatment course and one additional treatment as part of the retreatment (RT) course. The first treatment, followed by a 1-hour dwell time, was given to all subjects at Visit 1. At the end of hemodialysis at Visit 1, eligible subjects had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).

Drug: Tenecteplase

Interventions

Tenecteplase DRUG

2 mL (2 mg) of reconstituted lyophilized tenecteplase instilled into each lumen of the HD catheter.

Tenecteplase

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically stable, in the opinion of the investigator
• Use of a cuffed, tunneled HD catheter
• HD prescribed at a blood flow rate (BFR) of ≥300 mL/min
• Baseline BFR (at any time during the first 60 minutes of HD) of \<300 mL/min at an associated pre-pump negative arterial pressure in the range between and including -240 mmHg and -280 mmHg
• Baseline BFR (at any time during the first 60 minutes of HD) at least 25 mL/min below the prescribed BFR
• Demonstrated BFR of ≥300 mL/min (using catheter lines in the customary direction) at an arterial pressure in the range of 0 to -280 mmHg in at least one HD session in the 14 days prior to Visit 1
• Anticipated use of the same catheter for at least four consecutive HD sessions, on the same type and model of HD apparatus
• Able to have fluids infused at the volume necessary to instill study drug into the HD catheter

You may not qualify if:

• HD catheter with sustainable BFR of ≥300 mL/min following subject repositioning
• HD catheter inserted \<2 days prior to screening
• Evidence of a mechanical, non-thrombotic cause of HD catheter dysfunction (e.g., kink in the catheter or suture constricting the catheter) or dysfunction caused by known fibrin sheath
• Use of an implantable port
• HD catheter that is internally coated with any therapeutic agent (e.g., the Decathlon™ Gold catheter)
• Anticipated use of catheter for any other type of diagnostic or therapeutic procedure (i.e., other than HD) during study drug treatment
• Previously treated in this study or any tenecteplase catheter clearance trial
• Use of any investigational drug or therapy (defined as any drug or therapy that is not FDA approved) within 28 days prior to screening
• Use of a fibrinolytic agent (e.g. alteplase, tenecteplase, reteplase, or urokinase) within 7 days prior to Visit 1
• Known to be pregnant or breastfeeding at screening or at Visit 1
• Known bacteremia or known or suspected infection in the HD catheter
• Known history of any of the following: intracranial hemorrhage (within the previous 3 years), intracranial aneurysm, or arteriovenous malformation
• Use of heparin (unfractionated or low molecular weight) or other anticoagulants (e.g., for the treatment of heparin-induced thrombocytopenia) within 24 hours prior to Visit 1, except for heparin used only during HD or for prophylaxis (e.g., heparin lock or deep vein thrombosis prophylaxis)
• Subjects treated with warfarin only: international normalized ratio (INR) \>3.0 within 7 days prior to Visit 1, or a target INR range that allows for an INR \>3.0
• Initiation of or increase in dose of Plavix® (clopidogrel bisulfate) within 7 days prior to Visit 1

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Interventions

Tenecteplase

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800-821-8590

Study Officials

• Barbara Gillespie, MD, FASN

  Quintiles, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 6, 2006
• Study Start: November 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: January 12, 2017
• Results First Posted: August 2, 2011

Record last verified: 2016-11