Efficacy and Safety of Actilyse 2 mg/ 2 ml in Comparison to Saline Solution in Patients With Central Venous Access Device Occlusion

A Multicenter, Open-label, Randomised, Clinical Trial to Compare the Efficacy and Safety of Actilyse 2 mg/ 2 ml Versus Saline Solution in Restoring Function of an Occluded Central Venous Access Device

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

Study Overview

• Status: Completed
• Conditions: Vascular Access Devices; Catheter Obstruction
• Intervention / Treatment: Drug: Actilyse; Drug: Actilyse; Drug: Actilyse; Drug: Saline solution

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Akhangelsk, Russian Federation
    • 135.323.1 Boehringer Ingelheim Investigational Site
  • Krasnodar, Russian Federation
    • 135.323.2 Boehringer Ingelheim Investigational Site
  • Krasnoyarsk, Russian Federation
    • 135.323.3 Boehringer Ingelheim Investigational Site
  • Samara, Russian Federation
    • 135.323.5 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 135.323.7 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Actilyse 2 mg/2 ml; First dose of Actilyse 2mg/2ml will be given at time 0. Second dose will be given at 120 if CVAD function has not been restored.	Drug: Actilyse; Actilyse 2mg/2ml will be given if the CVAD has not been restored at time 120min.; Drug: Actilyse; Instil Actilyse 2 mg/ 2 ml into the dysfunctional CVAD at time O.; Drug: Actilyse; Second dose of Actilyse 2mg/2ml will be given if CVAD has not been restored at time 120min.
Sham Comparator: Saline solution (NaCl 0.9%); Saline solution will be given at time 0. First dose of Actilyse 2mg/2ml will be given to patients if CVAD function has not been restored.	Drug: Actilyse; Actilyse 2mg/2ml will be given if the CVAD has not been restored at time 120min.; Drug: Actilyse; Instil Actilyse 2 mg/ 2 ml into the dysfunctional CVAD at time O.; Drug: Actilyse; Second dose of Actilyse 2mg/2ml will be given if CVAD has not been restored at time 120min.; Drug: Saline solution; Instil Saline solution 2 ml into the disfunctional CVAD once at time O only for patients enrolled in Group II

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	120 minutes after first drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	30 minutes after first drug administration
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)	150 minutes after first drug administration
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)	240 minutes after first drug administration
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.	0 minutes and 240 minutes

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 1, 2013
• First Submitted That Met QC Criteria: October 8, 2013
• First Posted (Estimate): October 9, 2013

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 16, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: 135.323