t-PA Prophylaxis to Prevent Catheter-associated Thrombosis and Infection (TOPCAT)
Primary Purpose
Central Venous Catheter Thrombosis, Central Venous Catheter Associated Bloodstream Infection
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
alteplase (recombinant t-PA)
Heparin
Sponsored by
About this trial
This is an interventional prevention trial for Central Venous Catheter Thrombosis
Eligibility Criteria
Inclusion Criteria:
- Age 0 - ≤ 18 years old
- PICU admission
- CVC placed within 72 hours of enrollment (tunneled such as peripherally inserted central catheter (PICC), Broviac or Hickman, or untunneled) and in place during hospitalization
Exclusion Criteria:
- Pregnancy
- Non-English-speaking subjects and/or parent/guardian
- Platelet count < 20,000
- Active CVC infection-defined as positive blood culture from the in -situ CVC at time of enrollment
- Current radiographically confirmed VTE
- Currently receiving treatment doses of anticoagulation (heparin infusion >15U/kg/hr, enoxaparin injections >=2mg/kg/day or >=60mg/day)
- CVC diameter <1.9 Fr
- Current or previous diagnosis of Heparin Induced Thrombocytopenia or allergy to heparin or t-PA
- Med-a-port catheters
Sites / Locations
- Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
alteplase
Heparin
Arm Description
patients will receive 30 min-4 hours dwells of alteplase (recombinant t-PA) (2mg/2ml, up to 2mg per dose) to central venous catheter every 3 days (maximum 10 doses)
patients will receive 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses)
Outcomes
Primary Outcome Measures
Catheter-associated Venous Thrombosis
Catheter-associated Venous Thrombosis upon ICU discharge or 30 days
Catheter-associated Bloodstream Infection
CLABSI
Secondary Outcome Measures
Episodes of CVC Dysfunction
Episodes of CVC dysfunction
Off Study Use of t-PA
off study use
Clinical Bleeding
clinically significant bleeding
Full Information
NCT ID
NCT03672006
First Posted
September 13, 2018
Last Updated
June 21, 2021
Sponsor
Medical College of Wisconsin
1. Study Identification
Unique Protocol Identification Number
NCT03672006
Brief Title
t-PA Prophylaxis to Prevent Catheter-associated Thrombosis and Infection
Acronym
TOPCAT
Official Title
Tissue Plasminogen Activator Dwells to Reduce Catheter-associated Thrombosis and Infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
April 22, 2019 (Actual)
Primary Completion Date
December 15, 2019 (Actual)
Study Completion Date
December 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this pilot study is to test feasibility of concept, consent and enrollment rates, and mechanics of study designed to assess if intra-catheter dwells of tissue plasminogen activator (t-PA) is effective in decreasing the rate of clinically diagnosed central line associated blood stream infection (CLABSI) or venous thromboembolism (VTE) in central venous catheters (CVC) compared to standard of care heparin dwell.
Detailed Description
This pilot study Children's Hospital of Wisconsin will be a prospective, blinded, randomized controlled trial enrolling 20 patients in the pediatric intensive care unit (PICU) with a newly placed central venous catheter (CVC) to receive t-PA or heparin (current standard of care and defined as placebo for this study) to dwell for a minimum of 30 minutes every three days until catheter removal or discharge from the PICU. Primary outcomes would be central line associated blood stream infection (CLABSI) or venous thromboembolism (VTE). Secondary outcomes would be episodes of CVC dysfunction, off study use of t-PA, and bleeding.
Any patient admitted to the PICU and meeting the inclusion criteria will be approached for consent within 72 hours CVC placement. Randomization and administration of study drug/placebo treatment will be initiated within 24 hours of enrollment.
After randomization, study drug/heparin will be infused in the CVC for a dwell duration of 30 minutes-4 hours and then withdrawn (lock therapy) every 3 days until discharge from the PICU, CVC removal or a maximum of 10 doses received. Additional lumens will be treated on subsequent days. Any lumen requiring continuous infusion of vaso-active medication will not receive dwell therapy, evaluated on a day-to-day basis. Timing of instillation of study dwell medication will be adjusted so as not to interfere with medications for patient care.
This single center, pilot study will enroll 20 subjects.
Procedures to be completed for this study are as follows:
After informed consent/assent, the patient will be randomized and assigned to either the treatment arm (t-PA lock) or placebo arm (heparin lock). Randomization will be stratified by age (<5 or ≥5 years old). To maintain the blind, randomization will be done in the investigational pharmacy prior to the dispensing of the study drug/heparin.
Study Treatment and Dosing In subjects randomized to the t-PA, dosing and administration will comply with the Children's Hospital and Health System (CHHS) Policy and Procedure Protocol t-PA Administration for Central Venous Access Devices (CVAD); subjects randomized to the standard of care heparin group will receive an equivalent volume for weight of heparin 10U/ml. The CVC should be flushed with normal saline prior to infusion of study drug/placebo. After dwelling time of 30 minutes-4 hours, study drug/placebo should be withdrawn, check for blood return in CVC and flush line with normal saline as per policy. Each lumen of multi-lumen CVC should be treated every 3 days until patient discharge from PICU, removal of CVC, or a maximum of 10 doses of study drug/placebo are received.
Patient weight Volume Study drug/Placebo 0-10kg 0.5ml 10-20kg 1 ml >20kg 2 ml
These doses by body weight have been approved by the FDA for and CHHS Patient Care Protocol (tPA Administration for Central Venous Access Devices (CVADs) for use in children with CVC and are not associated with significant bleeding. If a 2mg (ml) dose of t-PA is administered by bolus injection directly into the systemic circulation, rather than as a dwell within the CVC, the drug concentration would return to endogenous levels with 30 minutes.
Ultrasound imaging At the end of the study period, a noninvasive ultrasound with doppler will be performed to assess for asymptomatic thrombosis in the blood vessel of the CVC location.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Central Venous Catheter Thrombosis, Central Venous Catheter Associated Bloodstream Infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Centralized pharmacy will prepare and blind the study drug (t-PA) and the control (heparin)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
alteplase
Arm Type
Experimental
Arm Description
patients will receive 30 min-4 hours dwells of alteplase (recombinant t-PA) (2mg/2ml, up to 2mg per dose) to central venous catheter every 3 days (maximum 10 doses)
Arm Title
Heparin
Arm Type
Active Comparator
Arm Description
patients will receive 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses)
Intervention Type
Biological
Intervention Name(s)
alteplase (recombinant t-PA)
Other Intervention Name(s)
tpa
Intervention Description
Medication administered to dwell in central venous catheter
Intervention Type
Drug
Intervention Name(s)
Heparin
Other Intervention Name(s)
control
Intervention Description
Medication administered to dwell in central venous catheter
Primary Outcome Measure Information:
Title
Catheter-associated Venous Thrombosis
Description
Catheter-associated Venous Thrombosis upon ICU discharge or 30 days
Time Frame
30 days or ICU discharge
Title
Catheter-associated Bloodstream Infection
Description
CLABSI
Time Frame
30 days or ICU discharge
Secondary Outcome Measure Information:
Title
Episodes of CVC Dysfunction
Description
Episodes of CVC dysfunction
Time Frame
30 days or ICU discharge
Title
Off Study Use of t-PA
Description
off study use
Time Frame
30 days or ICU discharge
Title
Clinical Bleeding
Description
clinically significant bleeding
Time Frame
30 days or ICU discharge
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 0 - ≤ 18 years old
PICU admission
CVC placed within 72 hours of enrollment (tunneled such as peripherally inserted central catheter (PICC), Broviac or Hickman, or untunneled) and in place during hospitalization
Exclusion Criteria:
Pregnancy
Non-English-speaking subjects and/or parent/guardian
Platelet count < 20,000
Active CVC infection-defined as positive blood culture from the in -situ CVC at time of enrollment
Current radiographically confirmed VTE
Currently receiving treatment doses of anticoagulation (heparin infusion >15U/kg/hr, enoxaparin injections >=2mg/kg/day or >=60mg/day)
CVC diameter <1.9 Fr
Current or previous diagnosis of Heparin Induced Thrombocytopenia or allergy to heparin or t-PA
Med-a-port catheters
Facility Information:
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53201
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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t-PA Prophylaxis to Prevent Catheter-associated Thrombosis and Infection
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