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

Condition(s) targeted: Renal Insufficiency

Intervention: placebo (Drug); tenecteplase (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Genentech

Official(s) and/or principal investigator(s):
Barbara Gillespie, M.D., FASN, Study Director, Affiliation: Quintiles

Overall contact:
Trial Information Support Line, Phone: 888-662-6728

This is a Phase III, randomized, double-blind, placebo-controlled study that will be conducted at approximately 40 centers in the United States. Approximately 150 subjects ≥ 16 years of age who require HD and have a dysfunctional HD catheter will be enrolled in the study.

Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment

Primary outcome:

Incidence of targeted adverse events from initial study drug administration through the start of Visit 2

Percentage of subjects who have treatment success with respect to BFR at Visit 1

Secondary outcome:

For subjects who have treatment success at Visit 1, the percentage of subjects who maintain catheter function at Visits 2 and 3

Percentage of subjects with a urea reduction ratio (URR) of ≥ 65% as assessed by pretreatment and post-HD blood urea nitrogen (BUN) measurements at Visit 1

For subjects who do not receive open-label tenecteplase at Visit 2, the percentage of subjects with a URR of ≥ 65% as assessed by pre- and post-HD BUN measurements at Visit 2

Change in BFR from baseline to the end of HD at Visit 1

Percentage of subjects who fall into each of the following categories defined by change in BFR from baseline to the end of HD at Visit 1: < 0 mL/min, 0-24 mL/min, 25-49 mL/min, 50-99 mL/min, 100-149 mL/min, and ≥ 150 mL/min

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 (during the first 30 minutes of HD) of < 300 mL/min (using catheter lines

in the customary direction, prior to any reversal of lines; see Section 3. 1.2. a) at an

arterial pressure of - 250 mmHg (or at institutional guidelines for maximum negative

arterial pressure, not to exceed 250 mmHg)

- Baseline BFR (during the first 30 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 - 250 mmHg in at least one HD session in the

7 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

Exclusion Criteria:

- 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 implanted in the subclavian vein

- Anticipated use of catheter for any other type of diagnostic or therapeutic procedure

(i. e., other than HD) during the course of the study

- Previously treated in this study or any tenecteplase catheter clearance trial

- Use of any investigational drug or therapy 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

- HD catheter with known or suspected infection

- History of any intracranial hemorrhage, aneurysm, or arteriovenous malformation

- Use of any heparin (unfractionated or low molecular weight) within 24 hours prior to

Visit 1, except for heparin used only during HD or for prophylaxis (e. g., heparin lock)

- Use of warfarin within 7 days prior to Visit 1, except for low-dose warfarin used for

prophylaxis

- Initiation of or increase in dose of Plavix(R) (clopidogrel bisulfate) within 7 days

prior to Visit 1

- Hemoglobin ≥ 13. 5 g/dL if on erythropoietin

- Platelet count < 75,000/uL

- At high risk for bleeding events or embolic complications (i. e., recent pulmonary

embolus, deep vein thrombosis, endarterectomy, or clinically significant right-to-left shunt) in the opinion of the investigator, or with known condition for which bleeding constitutes a significant hazard

- BFR of < 300 mL/min because of symptomatic hypotension

- Uncontrolled hypertension in the opinion of the investigator (e. g., systolic pressure

> 185 mmHg and diastolic pressure > 110 mmHg)

- Known hypersensitivity to tenecteplase or any component of the formulation

Trial Information Support Line, Phone: 888-662-6728

Southwest Kidney Inst PLC, Phoenix, Arizona 85006, United States; Recruiting
Monique Maturran, Phone: 480-610-6120, Email: mmaturan@swkidney.com

Southwest Kidney Inst PLC, Tempe, Arizona 85284, United States; Recruiting
Deborah Harrison, Phone: 480-610-6120, Email: research@swkidney.com

Arkansas Neph Serv-Hot Springs, Hot Springs, Arkansas 71901, United States; Recruiting
Holly Borel, Phone: 501-624-6000, Ext: 1144, Email: hborel@arkneph.com

La Puente Dialysis, La Puente, California 91744, United States; Recruiting
Delia Nassan, Phone: 213-481-2568, Email: dnassan@nicresearch.com

Mohammad Ismail, MD, Inc, Paramount, California 90713, United States; Recruiting

Norwalk Dialysis Center, Norwalk, California 90650, United States; Recruiting

Whittier Kidney Dialysis Ctr, Whittier, California 90603, United States; Recruiting

Univ of CO Health Science Ctr, Denver, Colorado 80220, United States; Recruiting
Beverly Farmer, Phone: 303-355-2510, Email: beverly.farmer@uchsc.edu

Davita Greater Waterbury, Waterbury, Connecticut 06708, United States; Recruiting

Genesis Clinical Res-Tampa, Tampa, Florida 33609, United States; Recruiting
Lourdes Medvid, Phone: 813-873-1016, Email: genclin@aol.com

Nephrology Assoc Centr Florida, Orlando, Florida 32804, United States; Recruiting
Marilyn Slater, Phone: 407-894-4693, Ext: 1245, Email: research@nacfla.com

Nephrology Assoc of So Miami, Miami, Florida 33173, United States; Recruiting

Outcomes Res Internat-Hudson, Hudson, Florida 34667, United States; Recruiting
Jennette Greco, Phone: 727-863-4069, Email: jgreco_research@yahoo.com

Outcomes Res Internat-Hudson, Hudson, Florida 34667, United States; Recruiting
Kathleen Gay, Phone: 727-863-4063, Email: kathleengay_research@yahoo.com

St Francis Med Ctr-Honolulu, Honolulu, Hawaii 96817, United States; Recruiting
Barbara Lew, Phone: 808-535-7613, Email: lew@clinicalpacific.com

Liberty Dialysis Meridian, Nampa, Idaho 83686, United States; Recruiting
Kirsten Vanderhalf, Phone: 208-846-7445, Email: kvanderhalf@biosekidney.com

North Suburban Nephrology, Gurnee, Illinois 60031, United States; Recruiting
Khalid Ghantous, Phone: 847-855-9152, Email: khalid.w.ghantous@comcast.net

Renal Care Associates, SC, Peoria, Illinois 61603, United States; Recruiting

Research By Design LLC, Evergreen Park, Illinois 60805, United States; Recruiting

Fort Wayne Neurological Center, Fort Wayne, Indiana 46805, United States; Recruiting
Joel Barra, Phone: 424-558-0603, Email: jbarra@airesearch.us

Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States; Recruiting
Cynthia Avery, Phone: 504-842-5931, Email: cavery@ochsner.org

Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States; Recruiting
Michele Washington, Phone: 504-988-4246, Email: mwashing@tulane.edu

Barnes Jewish Hospital, St. Louis, Missouri 63108, United States; Recruiting
Sue Dombek, Phone: 314-286-0819, Email: sdombek@wustl.edu

St. Louis University, Saint Louis, Missouri 63110, United States; Recruiting
Michelle Romano, Phone: 314-577-8765, Email: mromano3@slu.edu

Hackensack Univ Medical Center, Hackensack, New Jersey 07601, United States; Recruiting
Marie Reid, Phone: 201-996-2807, Email: mreid@humed.com

Silver Care Dialysis Center, Cherry Hill, New Jersey 08034, United States; Recruiting

West Pettigrew Dialysis Center, Durham, North Carolina 27705, United States; Recruiting

Bayview Nephrology, Erie, Pennsylvania 16507, United States; Recruiting

DaVita Lewistown Dialysis, Lewistown, Pennsylvania 17044, United States; Recruiting
Cristin Kwiterovich, Phone: 717-248-2344, Email: Cristin.Kwiterovich@davita.com

FMC-Mt Arry Kidney Center, Philadelphia, Pennsylvania 19119, United States; Recruiting

Franklin Dialysis/DaVitaPhilly, Philadelphia, Pennsylvania 19106, United States; Recruiting
Tracy Abraham, Phone: 215-922-2801, Email: tracy@rosserx.com

Temple University Hospital, Philadelphia, Pennsylvania 19140, United States; Recruiting
Sandy Amoroso, Phone: 215-707-3381, Email: sandra.amoroso@tuhs.temple.edu

Charleston Nephrology, North Charleston, South Carolina 29405, United States; Recruiting
Amy Perry, Phone: 843-821-4209, Email: perrya219@hotmail.com

G. Edward Newman MD PLLC, Knoxville, Tennessee 37923, United States; Recruiting

Nephrology Assoc-Chattanooga, Chattanooga, Tennessee 37404, United States; Recruiting
Kent Hulvey, Phone: 423-698-0927, Email: kent.hulvey@nephassociates.com

Fletcher Allen Health Care, South Burlington, Vermont 05403, United States; Recruiting
Desiree de Waal, Phone: 802-847-3203, Email: desiree.dewaal@vtmednet.org

Norfolk Dialysis Center, Norfolk, Virginia 23502, United States; Recruiting

Renal Care Partners-Fairfax, Fairfax, Virginia 22030, United States; Recruiting
Maria Obeid, Phone: 703-246-9505, Email: mobeidrn@aol.com

Fox Valley Nephrology Partners, Appleton, Wisconsin 54911, United States; Recruiting

Starting date: October 2006
Last updated: September 27, 2008