TROPICS 4: A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00396253
• Collaborator: (none)
• Enrollment: 223
• Arm: 1
• Duration (Months): 23

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dysfunctional Hemodialysis Catheters	Drug: Tenecteplase	Phase 3

Detailed Description

The study consisted of four visits that corresponded to consecutive HD sessions for each patient, as well as one follow-up visit. Patients could receive up to three treatments with open-label tenecteplase during the study: one or two treatments during an initial treatment course, and eligible patients whose catheter became dysfunctional again within 21 days of the first visit received an additional treatment as part of a retreatment (RT) course.

At Visit 1, patients eligible at the beginning of HD had 2 mL (2 mg) of tenecteplase instilled into each of the two lumens of the HD catheter. After a dwell time of 1 hour, study drug was withdrawn and all subjects underwent HD. The duration of the HD session was not fixed by the study protocol, but rather by the site's HD practice, physician orders, and individual patient response during the session. Patients who did not experience treatment success at the end of Visit 1 had 2 mL (2 mg) of tenecteplase instilled into each lumen of their catheter as part of the initial treatment course. The treatment was left to dwell for an extended time, until the second HD session at Visit 2 (up to 72 hours later). Patients who received extended-dwell tenecteplase had the treatment withdrawn from their catheter at the beginning of Visit 2. Patients underwent HD as prescribed or to the extent possible.

Patients who had treatment success at Visit 1 or Visit 2 and had a recurrence of catheter dysfunction within 21 days of Visit 1 and met the re-treatment eligibility criteria had 2 mL (2 mg) of tenecteplase instilled into each lumen, followed by a 1-hour dwell time at re-treatment Visit 1.

Study Design

• Study Type: Interventional
• Actual Enrollment: 223 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open-Label Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

   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.

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

   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.

Secondary Outcome Measures

1. 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).]

   For patients with treatment success at Visit 1 or Visit 2, maintenance of catheter function at subsequent visits was defined as a BFR ≥ 300 mL/min and an increase of ≥ 25 mL/min from baseline BFR (without reversal of lines), at an associated target arterial pressure in the range of 0 to -280 mmHg at the beginning of that HD session (within the first 30 minutes).

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.]

   The urea reduction ratio (URR) was calculated from measurements of blood urea nitrogen (BUN) as follows: (Pre-treatment BUN) - (Post-HD BUN) * 100% / (Pre-treatment BUN) Pre-treatment URR was assessed within 30-60 minutes after the initiation of HD and does not represent a true baseline value.

3. 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.]

   The urea reduction ratio (URR) at Visit 2 was calculated for those participants who did not receive extended-dwell tenecteplase at Visit 1 from measurements of blood urea nitrogen (BUN) as follows: (Pre-HD BUN) - (Post-HD BUN) * 100% / (Pre-HD BUN)

4. 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.]

   Change in Blood flow rate (BFR) is the BFR at the end of HD for Visit 1 - BFR at Baseline.

5. 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.]

   Patients who failed treatment at Visit 1 and were treated with extended-dwell tenecteplase were analyzed for Treatment Success at Visit 2. Treatment success at Visit 2 was defined as a BFR ≥ 300 mL/min, without line reversal, and increase of ≥ 25 mL/min from baseline BFR, 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.

6. Percentage of Participants Who Failed Treatment at Visit 1 With a Urea Reduction Ratio ≥ 65% at Visits 2 and 3 [Blood urea nitrogen measurements were taken prior to HD and at the end of HD at Visits 2 (2nd HD session, within 72 hours after visit 1) and 3 (3rd HD session, within 72 hours of Visit 2)]

   Patients who experienced treatment failure at the end of Visit 1 and were eligible for and treated with extended-dwell tenecteplase at Visit 1 were assessed for Urea Reduction Ratio (URR) at Visits 2 and 3. URR was calculated from blood urea nitrogen (BUN) measurements according to the following: (Pre-HD BUN) - (Post-HD BUN) * 100% / (Pre-HD BUN)

7. Change in Blood Flow Rate From Baseline to the End of HD at Visit 2 [Baseline (beginning of HD at Visit 1) to the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1).]

   Change in Blood flow rate (BFR) is the BFR at the end of HD for Visit 2 - BFR at Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: for the Study

• 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

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 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

• Hemoglobin ≥12.0 g/dL if on an erythropoiesis-stimulating agent (e.g., darbepoetin or erythropoietin) and the dose of the erythropoiesis-stimulating agent has not been held or reduced per institutional policy

• 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

• Known hypersensitivity to tenecteplase or any component of the formulation

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Barbara Gillespie, MD, FASN, Quintiles, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00396253
• Other Study ID Numbers: N3701g
• First Posted: Nov 6, 2006
• Last Update Posted: Jan 12, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by Genentech, Inc.: HD; TNKase; Hemodialysis; Catheter clearance
• Additional relevant MeSH terms: Tenecteplase

Study Results

Participant Flow

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Period Title: Overall Study
STARTED	223
COMPLETED	210
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Overall Participants	223
Age, Customized (participants) [Number]
< 17 years	1 0.4%
>= 17 years to < 65 years	120 53.8%
>= 65 years	102 45.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (16.3)
Gender (Count of Participants)
Female	124 55.6%
Male	99 44.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population, consisting of all enrolled patients who received at least one dose of study drug (tenecteplase).

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	223
Number [Percentage of participants]	34.1 15.3%

2. Primary Outcome

Title	Targeted Adverse Events From the Initial Study Drug Administration Through the Start of Visit 2 or Until Instillation of Extended-Dwell Tenecteplase
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	223
Intracranial hemorrhage	0
Major bleeding	0
Embolic event	0
Thrombosis	1
Catheter-related blood stream infection	2
Catheter-related complication	0

3. Secondary Outcome

Title	Percentage of Participants Who Maintained Catheter Function at Visits 2 and 3
Description	For patients with treatment success at Visit 1 or Visit 2, maintenance of catheter function at subsequent visits was defined as a BFR ≥ 300 mL/min and an increase of ≥ 25 mL/min from baseline BFR (without reversal of lines), at an associated target arterial pressure in the range of 0 to -280 mmHg at the beginning of that HD session (within the first 30 minutes).
Time Frame	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).

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population, who had treatment success at Visit 1. The n equals the number of subjects who had treatment success at Visit 1 and had assessment of catheter function for the given visit or who had a missing assessment due to starting the Retreatment course.

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	76
Visit 2 (n=72)	69.4 31.1%
Visit 3 (n=71)	62.0 27.8%

4. Secondary Outcome

Title	Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 1
Description	The urea reduction ratio (URR) was calculated from measurements of blood urea nitrogen (BUN) as follows: (Pre-treatment BUN) - (Post-HD BUN) * 100% / (Pre-treatment BUN) Pre-treatment URR was assessed within 30-60 minutes after the initiation of HD and does not represent a true baseline value.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	223
Number (95% Confidence Interval) [percentage of participants]	23.8 10.7%

5. Secondary Outcome

Title	Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 2
Description	The urea reduction ratio (URR) at Visit 2 was calculated for those participants who did not receive extended-dwell tenecteplase at Visit 1 from measurements of blood urea nitrogen (BUN) as follows: (Pre-HD BUN) - (Post-HD BUN) * 100% / (Pre-HD BUN)
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population who did not receive extended-dwell tenecteplase at Visit 1.

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	107
Number (95% Confidence Interval) [percentage of participants]	34.6 15.5%

6. Secondary Outcome

Title	Change in Blood Flow Rate From Baseline to the End of Hemodialysis at Visit 1
Description	Change in Blood flow rate (BFR) is the BFR at the end of HD for Visit 1 - BFR at Baseline.
Time Frame	Baseline (beginning of HD at Visit 1) to the end of HD at Visit 1.

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	223
Mean (Standard Deviation) [mL/min]	81.9 (123.84)

7. Secondary Outcome

Title	Percentage of Participants Who Failed Treatment at Visit 1 With Treatment Success at Visit 2
Description	Patients who failed treatment at Visit 1 and were treated with extended-dwell tenecteplase were analyzed for Treatment Success at Visit 2. Treatment success at Visit 2 was defined as a BFR ≥ 300 mL/min, without line reversal, and increase of ≥ 25 mL/min from baseline BFR, 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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Subjects in the MITT Population who were Treated with Extended-Dwell Tenecteplase at Visit 1.

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	116
Number (95% Confidence Interval) [percentage of participants]	49.1 22%

8. Secondary Outcome

Title	Percentage of Participants Who Failed Treatment at Visit 1 With a Urea Reduction Ratio ≥ 65% at Visits 2 and 3
Description	Patients who experienced treatment failure at the end of Visit 1 and were eligible for and treated with extended-dwell tenecteplase at Visit 1 were assessed for Urea Reduction Ratio (URR) at Visits 2 and 3. URR was calculated from blood urea nitrogen (BUN) measurements according to the following: (Pre-HD BUN) - (Post-HD BUN) * 100% / (Pre-HD BUN)
Time Frame	Blood urea nitrogen measurements were taken prior to HD and at the end of HD at Visits 2 (2nd HD session, within 72 hours after visit 1) and 3 (3rd HD session, within 72 hours of Visit 2)

Outcome Measure Data

Analysis Population Description

Subjects in the MITT Population who were Treated with Extended-Dwell Tenecteplase at Visit 1.

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	116
URR ≥ 65% at Visit 2	42.2 18.9%
URR ≥ 65% at Visit 3	33.6 15.1%

9. Secondary Outcome

Title	Change in Blood Flow Rate From Baseline to the End of HD at Visit 2
Description	Change in Blood flow rate (BFR) is the BFR at the end of HD for Visit 2 - BFR at Baseline.
Time Frame	Baseline (beginning of HD at Visit 1) to the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1).

Outcome Measure Data

Analysis Population Description

Subjects in the MITT Population Treated with Extended-Dwell Tenecteplase at Visit 1

Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
Measure Participants	116
Mean (Standard Deviation) [mL/minute]	117.1 (139.96)

Adverse Events

Time Frame	Begins at initiation of study treatment and ends upon completion of the second visit following the last administration of study treatment or at early termination from the study, whichever is earlier.
Adverse Event Reporting Description	MITT population. Note: The incidence of each AE/SAE is reported as the number of participants experiencing the event, not the number of occurrences for each AE/SAE.
Arm/Group Title	Tenecteplase
Arm/Group Description	At each treatment, patients had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Patients 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 patients at Visit 1. At the end of hemodialysis at Visit 1, eligible patients had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).
All Cause Mortality
	Tenecteplase
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tenecteplase
	Affected / at Risk (%)	# Events
Total	9/223 (4%)
Blood and lymphatic system disorders
Anaemia	1/223 (0.4%)
General disorders
Pain	1/223 (0.4%)
Infections and infestations
Bacteraemia	1/223 (0.4%)
Catheter Bacteraemia	1/223 (0.4%)
Gangrene	1/223 (0.4%)
Infected Skin Ulcer	1/223 (0.4%)
Sepsis	1/223 (0.4%)
Staphylococcal Bacteraemia	1/223 (0.4%)
Injury, poisoning and procedural complications
Procedural Pain	1/223 (0.4%)
Vascular disorders
Hypertension	1/223 (0.4%)
Other (Not Including Serious) Adverse Events
	Tenecteplase
	Affected / at Risk (%)	# Events
Total	36/223 (16.1%)
Gastrointestinal disorders
Nausea	4/223 (1.8%)
Constipation	1/223 (0.4%)
Diarrhoea	1/223 (0.4%)
Dyspepsia	1/223 (0.4%)
Vomiting	1/223 (0.4%)
General disorders
Asthenia	1/223 (0.4%)
Catheter Site Erythema	1/223 (0.4%)
Catheter Site Pain	1/223 (0.4%)
Chest Pain	1/223 (0.4%)
Chills	1/223 (0.4%)
Feeling Hot	1/223 (0.4%)
Oedema Peripheral	1/223 (0.4%)
Pyrexia	1/223 (0.4%)
Infections and infestations
Bacteraemia	1/223 (0.4%)
Gangrene	1/223 (0.4%)
Abdominal Abscess	1/223 (0.4%)
Central Line Infection	1/223 (0.4%)
Upper Respiratory Tract Infection	1/223 (0.4%)
Injury, poisoning and procedural complications
Contusion	1/223 (0.4%)
Device Breakage	1/223 (0.4%)
Investigations
Body Temperature Increased	1/223 (0.4%)
Musculoskeletal and connective tissue disorders
Muscle Spasms	2/223 (0.9%)
Arthralgia	1/223 (0.4%)
Back Pain	1/223 (0.4%)
Muscular Weakness	1/223 (0.4%)
Musculoskeletal Pain	1/223 (0.4%)
Nervous system disorders
Headache	4/223 (1.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/223 (0.4%)
Epistaxis	1/223 (0.4%)
Skin and subcutaneous tissue disorders
Pruritus	2/223 (0.9%)
Blister	1/223 (0.4%)
Vascular disorders
Hypertension	2/223 (0.9%)
Hypotension	3/223 (1.3%)
Haemodynamic Instability	2/223 (0.9%)
Hot Flush	1/223 (0.4%)
Venous Thrombosis Limb	1/223 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.