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

Condition(s) targeted: Renal Insufficiency

Intervention: 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: Genentech

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

This is a Phase III, open-label study that will be conducted at approximately 60 centers in the United States and Canada. Approximately 225 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, Open-Label Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis Catheters

Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment

Primary outcome:

For subjects who do not receive extended-dwell tenecteplase at Visit 1, the 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 extended-dwell tenecteplase at Visit 1, 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 for the Study:

- Able to provide written informed consent/assent and comply with the study assessments

for the full duration of the study

- Age ≥ 16 years

- 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) 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 for the Study:

- 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 lactating 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

Inclusion Criteria for the Retreatment Course:

- Treatment success at Visit 1 or Visit 2

- Clinically stable, in the opinion of the investigator

- Continued use of the same cuffed, tunneled HD catheter (i. e., the catheter the subject

had in place during the initial treatment course)

- HD prescribed at a BFR of ≥ 300 mL/min

- RT baseline BFR of < 300 mL/min (using catheter lines in the customary direction,

prior to any reversal of lines) at an arterial pressure of - 250 mmHg (or at

institutional guidelines for maximum negative arterial pressure, not to exceed 250 mmHg)

- RT baseline BFR at least 25 mL/min below the prescribed BFR

- Anticipated use of the same catheter for at least three 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 for the Retreatment Course:

- HD catheter with sustainable BFR of ≥ 300 mL/min following subject repositioning

- 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

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

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

- Use of any investigational drug or therapy other than tenecteplase within 21 days

prior to RT Visit 1

- Use of a fibrinolytic agent other than tenecteplase in this study (e. g. alteplase,

reteplase, or urokinase) within 7 days prior to RT Visit 1

- Known to be pregnant or lactating at RT Visit 1

- 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

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

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

for prophylaxis

- Initiation of or increase in dose of clopidogrel bisulfate within 7 days prior to RT

Visit 1

- Known hemoglobin ≥ 13. 5 g/dL between initial treatment course and RT Visit 1 if on

erythropoietin

- Known platelet count < 75,000/uL between initial treatment course and RT Visit 1

- 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

FMC Rio Piedras Dialysis Ctr, San Juan 00296, Puerto Rico; Recruiting
Maria Guerrero, Phone: 787-763-7423, Email: mariacguerrero@yahoo.com

Fresenius Medical Care, Humacao 00792, Puerto Rico; Recruiting
Amavelyn Rodriguez, Phone: 787-746-7441

University of South Alabama, Mobile, Alabama 36617, United States; Recruiting
Sue Karns, Phone: 251-377-6488, Email: skarns@usouthal.edu

Foothills Medical Centre, Calgary, Alberta T2N 2T9, Canada; Recruiting
Janice Mackay, Phone: 403-944-9882, Email: janice.mackay@calgaryhealthregion.ca

Royal Inland Hosp-Kamloods, Kamloods, British Columbia V2C 2T1, Canada; Recruiting
Judy Vicic, Phone: 250-314-2849, Email: judy.vicic@interiorhealth.ca

Kidney Center, Inc, Simi Valley, California 93065, United States; Recruiting
Anita Guerrero, Phone: 805-584-2411, Email: luna@kidneycenter.com

Stamford Nephrology, Stamford, Connecticut 06902, United States; Recruiting
Patricia Parry, Phone: 203-276-5963, Email: pparry@stamhealth.org

Nephrology Assoc Rsch Ctr, LLC, Panama City, Florida 32401, United States; Recruiting

Kidney Care Assoc-Augusta, Augusta, Georgia 30901, United States; Recruiting
Delia Marshall, Phone: 706-722-6900, Email: dmarshall@nephrology-associates.com

Univ of Chicago, Chicago, Illinois 60617, United States; Recruiting
Katrina Hebert, Phone: 773-834-5832, Email: Katrina.Hebert@uchospitals.edu

Indiana Medical Associates, Fort Wayne, Indiana 46804, United States; Recruiting
Christine Bowers, Phone: 260-403-0790, Email: christineb@indianamedical.com

Nephrology, Inc., Mishawaka, Indiana 46545, United States; Recruiting
Cindy Kay Nagy, Phone: 574-273-6787, Email: cnagy@nephine.com

Univ of Kansas Dialysis Ctr, Westwood, Kansas 66205, United States; Recruiting

Renal Associates-Baton Rouge, Baton Rouge, Louisiana 70884, United States; Recruiting
Lea Fuchs, Phone: 225-761-4507, Email: lfuchs@renalassociates.com

South Shreveport Dialysis Ctr, Shreveport, Louisiana 71106, United States; Recruiting
Yeona DaCosta Auld, Phone: 318-220-9792, Email: yauld@nwln.com

Caritas St. Elizabeth Med Ctr, Boston, Massachusetts 02135, United States; Recruiting
Karen Rider, Phone: 617-789-5136, Email: karen_rider@cchcs.org

Henry Ford Hospital, Detroit, Michigan 48202, United States; Recruiting
Nicole Smiley, Phone: 313-916-2806, Email: nsmiley1@hfhs.org

William Beaumont Hospital, Royal Oak, Michigan 48073, United States; Recruiting
Cynthia Turzewski, Phone: 248-551-9446, Email: cynthia.twzewski@beaumont.edu

Nephrology Associates, Columbus, Mississippi 39705, United States; Recruiting
Cathy Pace, Phone: 662-329-3838, Email: naresearch@bellsouth.net

FMC Metro N Dialysis-St Louis, Florissant, Missouri 63033, United States; Recruiting
Sally Stephens, Phone: 314-831-7990, Email: sally.stephens@fmc-na.com

St Joseph's Regional Med Ctr, Paterson, New Jersey 07503, United States; Recruiting
Bogdana Dikovytska, Phone: 973-569-6413, Email: kikovytb@sjmmc.org

Brookdale University Hospital, Brooklyn, New York 11212, United States; Recruiting
Barbara Mader, Phone: 718-495-4680, Ext: 101, Email: bkmader@yahoo.com

Clinical Res Dev-Springfield, Springfield Gardens, New York 11413, United States; Recruiting
Judith Wills, Phone: 718-276-4750, Email: jspencewills@aol.com

State University of New York, East Setauket, New York 11733, United States; Recruiting
Jacqueline Skarre, Phone: 631-444-9033, Email: jskarre@notes.cc.sunysb.edu

Upper Manhattan Dialysis Ctr, New York, New York 10025, United States; Recruiting
Saba Talib, Phone: 212-501-8100

Winthrop Univ Hospital, Mineola, New York 11501, United States; Recruiting

ProMedica Health Sys-Toledo, Toledo, Ohio 43606, United States; Recruiting
Vickie Snyder, Phone: 419-291-5757, Email: vickie.snyder@promedica.org

Sunnybrook Health Sciences Cen, Toronto, Ontario MYN 3M5, Canada; Recruiting
Fahema Ahmadzai, Phone: 416-480-6100, Ext: 7226, Email: fahema.ahmadzai@sunnybrook.ca

Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, United States; Recruiting
Marcia Goldstein, Phone: 215-456-6970, Email: goldtstein@einstein.edu

Renal Care of Erie, Erie, Pennsylvania 16502, United States; Recruiting
Jamie Wilshire, Phone: 814-455-6455, Ext: 21

Renal Endoc Assoc-Pittsburg, Pittsburg, Pennsylvania 15224, United States; Recruiting
Jaquita Marlin, Phone: 412-683-4550, Ext: 130, Email: jmarlin@reapc.com

Centre Hospitalier Regional, Trois Riviere, Quebec G8Z-3R9, Canada; Recruiting
Lyne Dufresne, Phone: 819-370-1190, Email: lynn.dufresne@sympatico.ca

Charles Lemoyne Hosp-Quebec, Greenfield Park, Quebec J4V 2H1, Canada; Recruiting
Jacinthe Martineau, Phone: 450-466-5000, Ext: 3365

Hopital du Sacre Coeur de Mont, Montreal, Quebec H4J 1C5, Canada; Recruiting
Patrick Roy, Phone: 514-338-2222, Email: patrick.roy@usherbrooke.ca

Hospital St-Luc du CHUM, Montreal, Quebec J3V6C8, Canada; Recruiting
Marie-Line Caron, Phone: 514-890-8000, Email: marie-line.caron.chum@ssss.gouv.qc.ca

Regina General Hospital, Regina, Saskatchewan S4P-0W5, Canada; Recruiting
Cheryl Altwasser, Phone: 306-766-4113, Email: caltwasser@sasktel.net

Palmetto Neph-Orangeburg, Orangeburg, South Carolina 29118, United States; Recruiting
Donna Bishop, Phone: 803-531-2677, Email: riana@nteck.net

Dallas VA Medical Center, Dallas, Texas 75216, United States; Recruiting
Lynne Roetzer, Phone: 214-857-0230, Email: LynneM@va.gov

Scott & White Memorial Hosp, Temple, Texas 76508, United States; Recruiting

South Arl Dialysis-Arlington, Arlington, Texas 76015, United States; Recruiting
Humeira Sherali, Phone: 817-465-8585, Email: hsherali@sadctx.com

Southwest Houston Research, Houston, Texas 77099, United States; Recruiting
Rowena Santillan, Phone: 281-598-2210, Email: rowena.santillan@swhresearch.com

Nephrology Assoc-N Virginia, Fairfax, Virginia 22033, United States; Recruiting
Roya Dadmarz, Phone: 703-961-0488, Email: rdadmarz@hotmail.com

Northwest Kidney Centers, Seattle, Washington 98122, United States; Recruiting
Cassandra Freeland, Phone: 206-543-2095, Email: freelandc@nwkidney.org

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