TROPICS 2: A Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00396318
• Collaborator: (none)
• Enrollment: 251
• Arm: 1

Study Details

Study Description

Brief Summary

This was a Phase III, open-label, single-arm study that was conducted at 43 centers in the United States and Canada. 251 adult and pediatric patients with dysfunctional central venous catheters (CVCs) were enrolled in the study and treated with one or two doses of tenecteplase.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 251 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open-Label, Single-Arm Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jun 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tenecteplase

Drug: tenecteplase; 2 mL of reconstituted lyophilized tenecteplase instilled into lumen of dysfunctional CVC. Patients weighing ≥ 30 kg received 2-mL instillations of tenecteplase (i.e., 2 mg of tenecteplase). Patients weighing < 30 kg received instillations of tenecteplase 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 Cumulative Restoration Rates of Central Venous Catheter (CVC) Function Following a Single Administration of Tenecteplase [120 minutes after first dose]

   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.

Secondary Outcome Measures

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

   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.

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

   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.

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

   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.

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

   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.

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

   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.

6. Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following Administration of One or Two Doses of Tenecteplase [Up to 120 minutes post-treatment (Dose 1 or Dose 2)]

   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.

7. Percentage of Patients Who Had Cumulative Restoration Rates Restoration Rates 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 CVC following patient repositioning

• Selected study CVC inserted < 2 days prior to treatment

• Selected study CVC implanted specifically for hemodialysis (HD) or internally coated with any therapeutic agent

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

• 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

• Known bacteremia or known or suspected infection in the CVC catheter

• Known history of intracranial hemorrhage (within the previous 3 years), intracranial aneurysm, or arteriovenous malformation

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

• 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 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: Barbara Gillespie, M.D., FASN, Quintiles, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00396318
• Other Study ID Numbers: N3699g
• First Posted: Nov 6, 2006
• Last Update Posted: Apr 27, 2011
• Last Verified: Mar 1, 2011

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

Study Results

Participant Flow

Pre-assignment Detail	Five patients were randomized but not treated, therefore the modified intent to treat (MITT) analysis population was 246.

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Period Title: At Least One Dose of Tenecteplase (MITT)
STARTED	246
COMPLETED	241
NOT COMPLETED	5
Period Title: At Least One Dose of Tenecteplase (MITT)
STARTED	246
COMPLETED	241
NOT COMPLETED	5
Period Title: At Least One Dose of Tenecteplase (MITT)
STARTED	241
COMPLETED	240
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Overall Participants	246
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.6 (26.4)
Age, Customized (participants) [Number]
< 2 years	10 4.1%
≥ 2 to < 17 years	62 25.2%
≥ 17 to < 65 years	111 45.1%
≥ 65 years	63 25.6%
Sex: Female, Male (Count of Participants)
Female	155 63%
Male	91 37%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates of Central Venous Catheter (CVC) Function Following a Single Administration 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	120 minutes after first dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Number [percentage of participants]	72.0 29.3%

2. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Single Administration 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	15 minutes after first dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Number [percentage of participants]	29.3 11.9%

3. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Single Administration 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	30 minutes after first dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Number [percentage of participants]	53.3 21.7%

4. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Second Administration 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	15 minutes after second dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Number [percentage of participants]	76.4 31.1%

5. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Second Administration 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	30 minutes after second dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Number [percentage of participants]	78.5 31.9%

6. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates of CVC Function Following a Second Administration 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	120 minutes after second dose

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Number [percentage of participants]	81.3 33%

7. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates 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 (Dose 1 or Dose 2)

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population

Arm/Group Title	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	246
Through first tenecteplase instillation	72.0 29.3%
Through second tenecteplase instillation	81.3 33%

8. Secondary Outcome

Title	Percentage of Patients Who Had Cumulative Restoration Rates Restoration Rates 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	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
Measure Participants	137
Number [percentage of participants]	81.0 32.9%

Adverse Events

Time Frame	The period during which SAEs and non-serious AEs were recorded began at the initiation of study treatment and ended at the follow-up visit 48-96 hours after treatment or at subject discontinuation from the study, whichever was earlier.
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	Tenecteplase
Arm/Group Description	2 mL tenecteplase administered to dwell for 15 (±5) minutes, after which central venous catheter (CVC) function was assessed. 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. In CVCs for which function was not restored, study drug was left to dwell for an additional 15 (±5) minutes (30 minutes post-treatment), after which CVC function was assessed as before. In CVCs for which function was not restored, study drug was left to dwell for an additional 90 (±10) minutes (120 minutes post-treatment), after which CVC function was assessed as before. If CVC function was not restored by 120 minutes after Dose 1, Dose 2 was given. Assessment of CVC function was repeated as before, after 15 (±5) minutes and, if needed, after 30 (±5) minutes and 120 (±10) minutes.
All Cause Mortality
	Tenecteplase
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tenecteplase
	Affected / at Risk (%)	# Events
Total	6/246 (2.4%)
General disorders
Pyrexia	2/246 (0.8%)
Immune system disorders
Hypersensitivity	1/246 (0.4%)
Infections and infestations
Catheter Related Infection	1/246 (0.4%)
Injury, poisoning and procedural complications
Device Malfunction	1/246 (0.4%)
Metabolism and nutrition disorders
Dehydration	1/246 (0.4%)
Other (Not Including Serious) Adverse Events
	Tenecteplase
	Affected / at Risk (%)	# Events
Total	26/246 (10.6%)
Blood and lymphatic system disorders
Neutropenia	3/246 (1.2%)
Febrile Neutropenia	1/246 (0.4%)
Eye disorders
Conjunctivitis	1/246 (0.4%)
Eye Discharge	1/246 (0.4%)
Gastrointestinal disorders
Nausea	2/246 (0.8%)
Abdominal Distension	1/246 (0.4%)
Abdominal Pain	1/246 (0.4%)
Constipation	1/246 (0.4%)
Diarrhoea	1/246 (0.4%)
Vomiting	1/246 (0.4%)
General disorders
Pyrexia	4/246 (1.6%)
Catheter Related Complication	1/246 (0.4%)
Injection Site Erythema	1/246 (0.4%)
Pain	1/246 (0.4%)
Immune system disorders
Drug Hypersensitivity	1/246 (0.4%)
Graft Versus Host Disease	1/246 (0.4%)
Infections and infestations
Nasopharyngitis	1/246 (0.4%)
Otitis Media	1/246 (0.4%)
Rash Pustular	1/246 (0.4%)
Streptococcal Bacteraemia	1/246 (0.4%)
Musculoskeletal and connective tissue disorders
Bone Pain	1/246 (0.4%)
Muscle Spasms	1/246 (0.4%)
Neck Pain	1/246 (0.4%)
Nervous system disorders
Dizziness	1/246 (0.4%)
Renal and urinary disorders
Dysuria	1/246 (0.4%)
Urinary Retention	1/246 (0.4%)
Respiratory, thoracic and mediastinal disorders
Increased Upper Airway Secretion	1/246 (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.