A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters

NCT00396032 | Completed Phase 3 Results

• 1 other identifier: N3700g
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a Phase III, randomized, double-blind, placebo-controlled study conducted at 37 centers in the United States. 150 subjects ≥ 16 years of age who required hemodialysis (HD) and had a dysfunctional HD catheter were enrolled in the study.

Conditions

Dysfunctional Hemodialysis Catheters

Keywords

HD; Hemodialysis; Catheter clearance; TNKase; Renal Insufficiency

Outcome Measures

Primary Outcomes (2)

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

  Treatment success is defined as BFR of ≥300 mL/min and an increase from baseline BFR of ≥25 mL/min at an associated target arterial pressure in the range of 0 to -280 mmHg 30 (±10) minutes prior to the end of HD and at the end of HD.

  Visit 1 of HD treatment

• Incidence of Targeted Adverse Events (AEs) From Initial Study Drug Administration Through the Start of Visit 2

  Targeted AEs were intracranial hemorrhages (ICHs), major bleeding, embolic events, thrombosis, catheter-related bloodstream infections (CRBSIs), and catheter related complications

  Visits 1 and 2 of consecutive HD treatments

Secondary Outcomes (3)

• Change in BFR From Baseline to the End of HD at Visit 1

  Visit 1 of HD treatment

• Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Extended Dwell Tenecteplase at Visit 1)

  Visit 2 of consecutive HD treatments

• Percentage of Subjects Who Had Treatment Success With Respect to BFR at Visit 2 (MITT Population With Open-label Tenecteplase at Visit 2)

  Visit 2 of consecutive HD treatments

Study Arms (2)

1

EXPERIMENTAL

Drug: tenecteplase

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

placebo DRUG

For the initial treatment, 2 mL of placebo instilled into each lumen of the HD catheter; subsequent treatments were 2 mL of open-label tenecteplase

2

tenecteplase DRUG

For the initial treatment, 2 mL of reconstituted lyophilized tenecteplase instilled into each lumen of the HD catheter; subsequent treatments were 2 mL of open-label tenecteplase

1

Eligibility Criteria

• Age: 16 Years+
• 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 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 A laboratory test to confirm the INR must have been performed within 7 days prior to Visit 1.
• Initiation of or increase in dose of Plavix® (clopidogrel bisulfate) within 7 days prior to Visit 1

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (1)

• Tumlin J, Goldman J, Spiegel DM, Roer D, Ntoso KA, Blaney M, Jacobs J, Gillespie BS, Begelman SM. A phase III, randomized, double-blind, placebo-controlled study of tenecteplase for improvement of hemodialysis catheter function: TROPICS 3. Clin J Am Soc Nephrol. 2010 Apr;5(4):631-6. doi: 10.2215/CJN.06520909. Epub 2010 Feb 4.

  PMID: 20133491 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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, M.D., FASN

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 6, 2006
• Study Start: October 1, 2006
• Primary Completion: December 1, 2008
• Last Updated: June 3, 2010
• Results First Posted: June 3, 2010

Record last verified: 2010-05