Dysfunctional Central Venous Access Catheters
Conditions
Keywords
TNKase, CVA, CVAD, Central venous access catheter, CVA catheter
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).
Interventions
DRUGplacebo
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).
DRUGtenecteplase
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).
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 10 kg) withdrawn from the selected study CVC following patient repositioning * Selected study CVC inserted \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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Participant flow
Pre-assignment details
Three patients were randomized but not treated, therefore the modified intent to treat (MITT) analysis population was 97.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) 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. | 47 |
| Tenecteplase + Tenecteplase + Placebo (TTP) 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. | 50 |
| Total | 97 |
Baseline characteristics
| Characteristic | Placebo + Tenecteplase + Tenecteplase (PTT) | Tenecteplase + Tenecteplase + Placebo (TTP) | Total |
|---|---|---|---|
| Age Continuous | 42.2 years STANDARD_DEVIATION 28.3 | 37.1 years STANDARD_DEVIATION 26.6 | 39.6 years STANDARD_DEVIATION 27.4 |
| Age, Customized ≥ 17 to < 65 years | 17 participants | 20 participants | 37 participants |
| Age, Customized ≥ 2 to < 17 years | 14 participants | 16 participants | 30 participants |
| Age, Customized < 2 years | 1 participants | 3 participants | 4 participants |
| Age, Customized ≥ 65 years | 15 participants | 11 participants | 26 participants |
| Sex: Female, Male Female | 31 Participants | 26 Participants | 57 Participants |
| Sex: Female, Male Male | 16 Participants | 24 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 47 | 14 / 50 |
| serious Total, serious adverse events | 1 / 47 | 2 / 50 |
Outcome results
Primary
Percentage of Patients Who Had Restoration of Central Venous Catheter (CVC) Function Following a Single Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of Central Venous Catheter (CVC) Function Following a Single Administration of Study Drug | 23.4 percentage of participants |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of Central Venous Catheter (CVC) Function Following a Single Administration of Study Drug | 60.0 percentage of participants |
p-value: 0.000295% CI: [18.4, 54.8]Cochran-Mantel-Haenszel
Secondary
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
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
Population: Number of patients (from MITT population) with restored CVC function during the treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | 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 | 81.5 Percentage of patients |
| Tenecteplase + Tenecteplase + Placebo (TTP) | 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 | 79.3 Percentage of patients |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase | Through first tenecteplase instillation | 72.3 percentage of participants |
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase | Through second tenecteplase instillation | 85.1 percentage of participants |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase | Through first tenecteplase instillation | 60.0 percentage of participants |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following Administration of One or Two Doses of Tenecteplase | Through second tenecteplase instillation | 88.0 percentage of participants |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug | 42.6 percentage of participants |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug | 70.0 percentage of participants |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug | 63.8 Percentage of patients |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug | 82.0 Percentage of patients |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug | 72.3 Percentage of patients |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Second Administration of Study Drug | 88.0 Percentage of patients |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug | 19.1 Percentage of patients |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug | 44.0 Percentage of patients |
p-value: 0.009395% CI: [7.1, 42.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug | 10.6 percentage of participants |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Single Administration of Study Drug | 22.0 percentage of participants |
p-value: 0.138595% CI: [-3.1, 25.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | 85.1 Percentage of patients |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | 88.0 Percentage of patients |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | 83.0 percentage of participants |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | 88.0 percentage of participants |
Secondary
Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug
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
Population: Modified intent to treat (MITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Tenecteplase + Tenecteplase (PTT) | Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | 85.1 Percentage of patients |
| Tenecteplase + Tenecteplase + Placebo (TTP) | Percentage of Patients Who Had Restoration of CVC Function Following a Third Administration of Study Drug | 88.0 Percentage of patients |