Catheter Obstruction, Vascular Access Devices
Conditions
Brief summary
This is a multicentre, open-label, randomised, phase III study designed to evaluate the efficacy and safety of Actilyse 2 mg/2 ml in the restoration of function of CVAD
Interventions
DRUGActilyse
Actilyse 2mg/2ml will be given if the CVAD has not been restored at time 120min.
DRUGSaline solution
Instil Saline solution 2 ml into the disfunctional CVAD once at time O only for patients enrolled in Group II
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients between 18 and 80 years, who signed a written informed consent * Patients with central venous access device occlusion, which occurred within 24-h before randomisation, where central venous access device is indicated for any of the following: fluid maintenance, chemotherapy, intravenous feeding, haemodialysis, long-term administration of antibiotics or other medication * Patients with central venous access device occlusion occurred within 24-h before randomisation. Central venous access device is defined by inability to withdraw at least 3 ml of blood from the central venous access device. If multiple lumens are occluded, investigators are to choose and treat only one lumen for the study. * Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice and the local legislation. Acceptable level of the following laboratory parameters: * hemoglobin ≥ 80 g/L; * total white blood cell count ≥ 2.0 x109/L; * platelets ≥ 50.0 x109/L; * fibrinogen ≥0.5 x lower limit of normal; * international normalized ratio \<2 x upper limit of normal; * activated partial thromboplastin time \<2 x upper limit of normal; * total protein ≥ 35 g/l; * alanine transaminase \<20 x upper limit of normal; * aspartate transaminase \<20 x upper limit of normal; * total bilirubin \<10 x upper limit of normal; * creatinine \<6 x upper limit of normal; * glucose \> 2.8 mmol/l.
Exclusion criteria
* Any clinical evidence of mechanical or non-thrombotic occlusion * High risk for bleeding events * High risk for embolic complications * Any condition for which bleeding constitutes a significant hazard or would be particularly difficult to manage * Administration of any fibrinolytic agent within 48 hours before start of study treatment * Patients who have had any of the following within the previous 48 hours before start of study treatment: * surgery * obstetrical delivery * percutaneous biopsy of viscera or deep tissues * puncture of non-compressible vessels * active internal bleeding * Patients who have thrombocytopenia, other hemostatic defects (including those secondary to severe hepatic or renal disease). * Pregnancy and lactation. * Previously known positive results from infectious serology for Human Immunodeficiency Virus (HIV) or hepatitis B surface antigen (HBsAg), or hepatitis C virus. * Known hypersensitivity to alteplase or gentamicin, or any excipient of Actilyse - Body weight \<30 kg. * Administration of any fibrinolytic agent within 48 hours before start of study treatment. * Participation in another investigational trial within 30 days prior to the Screening Visit. * Concomitant treatment with angiotensin-converting-enzyme inhibitors. * Impossibility to infuse fluids at the volume necessary to infuse study drug (2 ml) into the central venous access device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Restored CVAD Function at 120 Min After Administration of the First Dose of Study Medication | 120 minutes after first drug administration | Proportion (percentage) of patients with restored central venous access device (CVAD) function at 120 min after administration of the first dose of study medication (i.e. Actilyse® or saline solution). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Restored CVAD Function 30 Minutes After Administration of Study Medication at Time 0 | 30 minutes after first drug administration | Percentage of patients with restored CVAD function 30 minutes after administration of study medication at time 0 (i.e. Actilyse® or saline solution) |
| Restored CVAD Function 30 Minutes After Administration of the Second Dose of Study Medication Actilyse | 150 minutes after first drug administration | Percentage of patients with restored CVAD function 30 minutes after administration of the second dose of study medication Actilyse (150 minutes after time 0) |
| Restored CVAD Function 120 Minutes After Administration of the Second Dose of Study Medication Actilyse | 240 minutes after first drug administration | Percentage of patients with restored CVAD function 120 minutes after administration of the second dose of study medication Actilyse (240 minutes after time 0) |
| Percentage of Participants Who Achieved Restored CVAD Function After 1 Dose and 2 Doses, in Patients From the Actilyse Treatment Group. | 0 minutes and 240 minutes | This endpoint was defined as the number of doses required to achieve restored CVAD function in patients from the actilyse treatment group but was analysed as the percentage of participants who achieved restored CVAD function after 1 dose and 2 doses, in patients from the actilyse treatment group. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Actilyse Patients received one dose of Actilyse 2mg/2ml, administered intravenously, at time 0. A second dose was administered at 120 minutes if central venous access device (CVAD) function had not been restored. | 6 |
| Saline Solution + Actilyse Patients received one dose of saline solution (NaCl 0.9% - 2ml), administered intravenously, at time 0. A first dose of Actilyse 2mg/2ml was administered intravenously to patients at 120 minutes if central venous access device (CVAD) function had not been restored. | 10 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 3 |
Baseline characteristics
| Characteristic | Actilyse | Saline Solution + Actilyse | Total |
|---|---|---|---|
| Age, Continuous | 56.0 years | 63.9 years | 60.9 years |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 0 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 10 |
Outcome results
Primary
Proportion of Patients With Restored CVAD Function at 120 Min After Administration of the First Dose of Study Medication
Proportion (percentage) of patients with restored central venous access device (CVAD) function at 120 min after administration of the first dose of study medication (i.e. Actilyse® or saline solution).
Time frame: 120 minutes after first drug administration
Population: Full analysis set (FAS) which included all randomised patients who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Actilyse | Proportion of Patients With Restored CVAD Function at 120 Min After Administration of the First Dose of Study Medication | 83.3 percentage of participants |
| Saline Solution + Actilyse | Proportion of Patients With Restored CVAD Function at 120 Min After Administration of the First Dose of Study Medication | 10.0 percentage of participants |
95% CI: [23.3, 89.3]
Secondary
Percentage of Participants Who Achieved Restored CVAD Function After 1 Dose and 2 Doses, in Patients From the Actilyse Treatment Group.
This endpoint was defined as the number of doses required to achieve restored CVAD function in patients from the actilyse treatment group but was analysed as the percentage of participants who achieved restored CVAD function after 1 dose and 2 doses, in patients from the actilyse treatment group.
Time frame: 0 minutes and 240 minutes
Population: All patients in the FAS who were randomised to the Actilyse treatment group
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Actilyse | Percentage of Participants Who Achieved Restored CVAD Function After 1 Dose and 2 Doses, in Patients From the Actilyse Treatment Group. | After 1 dose of Actilyse | 83.3 percentage of participants |
| Actilyse | Percentage of Participants Who Achieved Restored CVAD Function After 1 Dose and 2 Doses, in Patients From the Actilyse Treatment Group. | After 2 doses of Actilyse | 16.7 percentage of participants |
Secondary
Restored CVAD Function 120 Minutes After Administration of the Second Dose of Study Medication Actilyse
Percentage of patients with restored CVAD function 120 minutes after administration of the second dose of study medication Actilyse (240 minutes after time 0)
Time frame: 240 minutes after first drug administration
Population: All patients in the FAS who did not have restored CVAD function 120 minutes after first drug administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Actilyse | Restored CVAD Function 120 Minutes After Administration of the Second Dose of Study Medication Actilyse | 100.0 percentage of participants |
| Saline Solution + Actilyse | Restored CVAD Function 120 Minutes After Administration of the Second Dose of Study Medication Actilyse | 77.8 percentage of participants |
Secondary
Restored CVAD Function 30 Minutes After Administration of Study Medication at Time 0
Percentage of patients with restored CVAD function 30 minutes after administration of study medication at time 0 (i.e. Actilyse® or saline solution)
Time frame: 30 minutes after first drug administration
Population: Full analysis set (FAS) which included all randomised patients who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Actilyse | Restored CVAD Function 30 Minutes After Administration of Study Medication at Time 0 | 66.7 percentage of participants |
| Saline Solution + Actilyse | Restored CVAD Function 30 Minutes After Administration of Study Medication at Time 0 | 0.0 percentage of participants |
95% CI: [20.7, 90.3]
Secondary
Restored CVAD Function 30 Minutes After Administration of the Second Dose of Study Medication Actilyse
Percentage of patients with restored CVAD function 30 minutes after administration of the second dose of study medication Actilyse (150 minutes after time 0)
Time frame: 150 minutes after first drug administration
Population: All patients in the FAS who did not have restored CVAD function 120 minutes after first drug administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Actilyse | Restored CVAD Function 30 Minutes After Administration of the Second Dose of Study Medication Actilyse | 100.0 percentage of participants |
| Saline Solution + Actilyse | Restored CVAD Function 30 Minutes After Administration of the Second Dose of Study Medication Actilyse | 55.6 percentage of participants |