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

Conditions

Dysfunctional Central Venous Access Catheters

Keywords

TNKase, CVA, CVAD, Central venous access catheter

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.

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Interventions

DRUGtenecteplase

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).

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

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 10 kg) withdrawn from the selected CVC following patient repositioning * Selected study CVC inserted \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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.

Participant flow

Pre-assignment details

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

Participants by arm

Arm	Count
Tenecteplase 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.	246
Total	246

Arm

Count

Tenecteplase

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.

246

Total

246

Withdrawals & dropouts

Period	Reason	FG000
At Least One Dose of Tenecteplase (MITT)	Subject withdrew consent	5

Baseline characteristics

Characteristic	Tenecteplase
Age Continuous	43.6 Years STANDARD_DEVIATION 26.4
Age, Customized ≥ 17 to < 65 years	111 participants
Age, Customized ≥ 2 to < 17 years	62 participants
Age, Customized < 2 years	10 participants
Age, Customized ≥ 65 years	63 participants
Sex: Female, Male Female	155 Participants
Sex: Female, Male Male	91 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	26 / 246
serious Total, serious adverse events	6 / 246