TROPICS 1: A Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00395876
• Collaborator: (none)
• Enrollment: 100
• Arms: 2

Study Details

Study Description

Brief Summary

This was a Phase III, randomized, double-blind, placebo-controlled study that was conducted at 24 centers in the United States and Canada. 100 adult and pediatric patients with dysfunctional central venous catheters (CVCs) were randomly assigned in a 1:1 ratio to receive an initial dose of either placebo (Arm A) or tenecteplase (Arm B).

Condition or Disease	Intervention/Treatment	Phase
Dysfunctional Central Venous Access Catheters	Drug: placebo; Drug: tenecteplase	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo + Tenecteplase + Tenecteplase (PTT)	Drug: placebo; 2 mL of placebo instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of placebo). Patients weighing < 30 kg received instillations of study drug equal to 110% of the internal lumen volume of the dysfunctional CVC. This dose was rounded to the nearest 0.1 mL and should not have exceeded 2 mL (2 mg).; Drug: tenecteplase; 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of tenecteplase). Patients weighing < 30 kg received instillations of study drug equal to 110% of the internal lumen volume of the dysfunctional CVC. This dose was rounded to the nearest 0.1 mL and should not have exceeded 2 mL (2 mg).
Experimental: Tenecteplase + Tenecteplase + Placebo (TTP)	Drug: placebo; 2 mL of placebo instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of placebo). Patients weighing < 30 kg received instillations of study drug equal to 110% of the internal lumen volume of the dysfunctional CVC. This dose was rounded to the nearest 0.1 mL and should not have exceeded 2 mL (2 mg).; Drug: tenecteplase; 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of study drug (i.e., 2 mg of tenecteplase). Patients weighing < 30 kg received instillations of study drug equal to 110% of the internal lumen volume of the dysfunctional CVC. This dose was rounded to the nearest 0.1 mL and should not have exceeded 2 mL (2 mg).

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Who Had Restoration of Central Venous Catheter (CVC) Function Following a Single Administration of Study Drug [120 minutes after first dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

Secondary Outcome Measures

1. Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug [15 minutes after first dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

2. Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug [30 minutes after first dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

3. Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug [15 minutes after second dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

4. Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug [30 minutes after second dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

5. Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug [120 minutes after second dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

6. Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug [15 minutes after third dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

7. Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug [30 minutes after third dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

8. Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug [120 minutes after third dose]

   Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

9. Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase [Up to 120 minutes post-treatment]

   Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

10. Percentage of Patients Who Had Restoration of CVC Function at Any Time During the Study and Who Maintained Catheter Patency the Next Time the Catheter Was Assessed, up to 7 Days Following the Last Dose of Tenecteplase [Up to 7 days post-treatment]

    Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinically stable, in the opinion of the investigator

• CVC occlusion

• Able to have fluids infused at the volume necessary to instill study drug into the CVC

Exclusion Criteria:

• Able to have 3 mL of blood (patients weighing ≥ 10 kg) or 1 mL of blood (patients weighing < 10 kg) withdrawn from the selected study CVC following patient repositioning

• Selected study CVC inserted < 2 days prior to treatment

• Selected study CVC known to be dysfunctional for > 7 days

• Selected study CVC implanted specifically for hemodialysis (HD)

• Use of a power injector on the selected study CVC during the study

• Evidence of mechanical, non-thrombotic occlusion of the selected study CVC (e.g., kink in the catheter or suture constricting the catheter)

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

• Use of any investigational drug or therapy within 28 days prior to treatment

• Use of a fibrinolytic agent (e.g., alteplase, tenecteplase, reteplase, or urokinase) within 24 hours prior to treatment

• Known to be pregnant or breastfeeding at screening

• CVC with known or suspected infection

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

• Use of heparin (unfractionated or low molecular weight) within 24 hours prior to treatment, except for use of intermittent or low-dose, continuous infusion of heparin to maintain catheter or vessel patency

• Use of warfarin within 7 days prior to treatment, except for low-dose warfarin used for prophylaxis

• Initiation of or increase in dose of Plavix® (clopidogrel bisulfate) within 7 days prior to treatment

• 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

• 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: Richard Levine, M.D.,

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00395876
• Other Study ID Numbers: N3698g
• First Posted: Nov 6, 2006
• Last Update Posted: Aug 10, 2010
• Last Verified: Jul 1, 2010

• Keywords provided by , ,: TNKase; CVA; CVAD; Central venous access catheter; CVA catheter
• Additional relevant MeSH terms: Tenecteplase

Study Results

Participant Flow

Pre-assignment Detail	Three patients were randomized but not treated, therefore the modified intent to treat (MITT) analysis population was 97.

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Period Title: Overall Study
STARTED	50	50
COMPLETED	47	50
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)	Total
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Total of all reporting groups
Overall Participants	47	50	97
Age, Customized (participants) [Number]
< 2 years	1 2.1%	3 6%	4 4.1%
≥ 2 to < 17 years	14 29.8%	16 32%	30 30.9%
≥ 17 to < 65 years	17 36.2%	20 40%	37 38.1%
≥ 65 years	15 31.9%	11 22%	26 26.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (28.3)	37.1 (26.6)	39.6 (27.4)
Sex: Female, Male (Count of Participants)
Female	31 66%	26 52%	57 58.8%
Male	16 34%	24 48%	40 41.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Who Had Restoration of Central Venous Catheter (CVC) Function Following a Single Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	120 minutes after first dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number [percentage of participants]	23.4 49.8%	60.0 120%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Tenecteplase + Tenecteplase (PTT), Tenecteplase + Tenecteplase + Placebo (TTP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Stratified by baseline weight (< 30 kg, ≥ 30 kg)
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	36.6
	Confidence Interval	() 95%; 18.4 to 54.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	15 minutes after first dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number [percentage of participants]	10.6 22.6%	22.0 44%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Tenecteplase + Tenecteplase (PTT), Tenecteplase + Tenecteplase + Placebo (TTP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1385
	Comments	Stratified by baseline weight (< 30 kg, ≥ 30 kg)
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.4
	Confidence Interval	() 95%; -3.1 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	30 minutes after first dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number [Percentage of patients]	19.1	44.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Tenecteplase + Tenecteplase (PTT), Tenecteplase + Tenecteplase + Placebo (TTP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0093
	Comments	Stratified by baseline weight (< 30 kg, ≥ 30 kg)
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	24.9
	Confidence Interval	() 95%; 7.1 to 42.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	15 minutes after second dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number (95% Confidence Interval) [percentage of participants]	42.6 90.6%	70.0 140%

5. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	30 minutes after second dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number (95% Confidence Interval) [Percentage of patients]	63.8	82.0

6. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	120 minutes after second dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number (95% Confidence Interval) [Percentage of patients]	72.3	88.0

7. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	15 minutes after third dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number (95% Confidence Interval) [percentage of participants]	83.0 176.6%	88.0 176%

8. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	30 minutes after third dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number (95% Confidence Interval) [Percentage of patients]	85.1	88.0

9. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug
Description	Restoration of CVC function was defined as successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	120 minutes after third dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Number (95% Confidence Interval) [Percentage of patients]	85.1	88.0

10. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase
Description	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	Up to 120 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	47	50
Through first tenecteplase instillation	72.3 153.8%	60.0 120%
Through second tenecteplase instillation	85.1 181.1%	88.0 176%

11. Secondary Outcome

Title	Percentage of Patients Who Had Restoration of CVC Function at Any Time During the Study and Who Maintained Catheter Patency the Next Time the Catheter Was Assessed, up to 7 Days Following the Last Dose of Tenecteplase
Description	Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Time Frame	Up to 7 days post-treatment

Outcome Measure Data

Analysis Population Description

Number of patients (from MITT population) with restored CVC function during the treatment period

Arm/Group Title	Placebo + Tenecteplase + Tenecteplase (PTT)	Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.	Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
Measure Participants	27	29
Number (95% Confidence Interval) [Percentage of patients]	81.5	79.3

Adverse Events

Adverse Event Reporting Description	Modified intent to treat (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	Placebo + Tenecteplase + Tenecteplase (PTT)		Tenecteplase + Tenecteplase + Placebo (TTP)
Arm/Group Description	Initial dose: 2 mL of placebo instilled into lumen of dysfunctional central venous cathether (CVC). If CVC function was not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function was not restored, patient received third dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.		Initial dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received second dose: 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. If CVC function not restored, patient received third dose: 2 mL of placebo instilled into lumen of dysfunctional CVC. Restoration of CVC function was defined as the successful withdrawal of at least 3 mL of blood or fluid and infusion of 5 mL of normal saline in patients weighing ≥ 10 kg, and withdrawal of at least 1 mL of blood or fluid and infusion of 3 mL of normal saline in patients weighing < 10 kg.
All Cause Mortality
	Placebo + Tenecteplase + Tenecteplase (PTT)		Tenecteplase + Tenecteplase + Placebo (TTP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + Tenecteplase + Tenecteplase (PTT)		Tenecteplase + Tenecteplase + Placebo (TTP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/47 (2.1%)		2/50 (4%)
Blood and lymphatic system disorders
Pancytopenia	0/47 (0%)		1/50 (2%)
Psychiatric disorders
Mental Status Changes	1/47 (2.1%)		0/50 (0%)
Vascular disorders
Venous Thrombosis	0/47 (0%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	Placebo + Tenecteplase + Tenecteplase (PTT)		Tenecteplase + Tenecteplase + Placebo (TTP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/47 (12.8%)		14/50 (28%)
Blood and lymphatic system disorders
Anaemia	0/47 (0%)		1/50 (2%)
Neutropenia	0/47 (0%)		1/50 (2%)
Thrombocytopenia	0/47 (0%)		1/50 (2%)
Cardiac disorders
Tachycardia	1/47 (2.1%)		0/50 (0%)
Gastrointestinal disorders
Diarrhoea	1/47 (2.1%)		1/50 (2%)
Vomiting	0/47 (0%)		2/50 (4%)
Abdonimal Pain	0/47 (0%)		1/50 (2%)
Abdominal Pain Upper	0/47 (0%)		1/50 (2%)
Epigastric Discomfort	0/47 (0%)		1/50 (2%)
Nausea	0/47 (0%)		1/50 (2%)
Stomatitis	0/47 (0%)		1/50 (2%)
General disorders
Catheter Site Pain	0/47 (0%)		2/50 (4%)
Asthenia	0/47 (0%)		1/50 (2%)
Axillary Pain	0/47 (0%)		1/50 (2%)
Catheter Site Oedema	0/47 (0%)		1/50 (2%)
Chest Pain	0/47 (0%)		1/50 (2%)
Fatigue	0/47 (0%)		1/50 (2%)
Oedema Peripheral	0/47 (0%)		1/50 (2%)
Pyrexia	1/47 (2.1%)		0/50 (0%)
Infections and infestations
Central Line Infection	0/47 (0%)		1/50 (2%)
Escherichia Sepsis	0/47 (0%)		1/50 (2%)
Investigations
Blood Lactate Dehydrogenase Increased	0/47 (0%)		1/50 (2%)
Platelet Count Decreased	0/47 (0%)		1/50 (2%)
Weight Decreased	0/47 (0%)		1/50 (2%)
Metabolism and nutrition disorders
Hypertriglycerideaemia	0/47 (0%)		1/50 (2%)
Musculoskeletal and connective tissue disorders
Back Pain	1/47 (2.1%)		0/50 (0%)
Bone Pain	0/47 (0%)		1/50 (2%)
Musculoskeletal Pain	1/47 (2.1%)		0/50 (0%)
Neck Pain	1/47 (2.1%)		0/50 (0%)
Pain in Extremity	1/47 (2.1%)		0/50 (0%)
Nervous system disorders
Dizziness	0/47 (0%)		2/50 (4%)
Burning Sensation	1/47 (2.1%)		0/50 (0%)
Syncope	0/47 (0%)		1/50 (2%)
Psychiatric disorders
Agitation	1/47 (2.1%)		0/50 (0%)
Anxiety	0/47 (0%)		1/50 (2%)
Renal and urinary disorders
Glycosuria	1/47 (2.1%)		0/50 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/47 (2.1%)		1/50 (2%)
Bradypnoea	1/47 (2.1%)		0/50 (0%)
Dyspnoea	0/47 (0%)		1/50 (2%)
Laryngospasm	0/47 (0%)		1/50 (2%)
Pneumothorax	1/47 (2.1%)		0/50 (0%)
Skin and subcutaneous tissue disorders
Dry Skin	1/47 (2.1%)		0/50 (0%)
Rash	1/47 (2.1%)		0/50 (0%)
Vascular disorders
Hypotension	1/47 (2.1%)		1/50 (2%)
Haematoma	1/47 (2.1%)		0/50 (0%)

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.