TOPCAT: t-PA Prophylaxis to Prevent Catheter-associated Thrombosis and Infection

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Completed
• CT.gov ID: NCT03672006
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 7.8
• Patients Per Site Per Month: 2.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Central Venous Catheter Thrombosis; Central Venous Catheter Associated Bloodstream Infection	Biological: alteplase (recombinant t-PA); Drug: Heparin	Phase 2

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After randomization, study drug/heparin will be infused in the CVC for a dwell duration of 30 minutes-4 hours and then withdrawn (lock therapy) every 3 days until discharge from the PICU, CVC removal or a maximum of 10 doses received.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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Centralized pharmacy will prepare and blind the study drug (t-PA) and the control (heparin)
• Primary Purpose: Prevention
• Official Title: Tissue Plasminogen Activator Dwells to Reduce Catheter-associated Thrombosis and Infection
• Actual Study Start Date: Apr 22, 2019
• Actual Primary Completion Date: Dec 15, 2019
• Actual Study Completion Date: Dec 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: alteplase 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)	Biological: alteplase (recombinant t-PA); Medication administered to dwell in central venous catheter; Other Names: tpa
Active Comparator: Heparin 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)	Drug: Heparin; Medication administered to dwell in central venous catheter; Other Names: control

Outcome Measures

Primary Outcome Measures

1. Catheter-associated Venous Thrombosis [30 days or ICU discharge]

   Catheter-associated Venous Thrombosis upon ICU discharge or 30 days

2. Catheter-associated Bloodstream Infection [30 days or ICU discharge]

   CLABSI

Secondary Outcome Measures

1. Episodes of CVC Dysfunction [30 days or ICU discharge]

   Episodes of CVC dysfunction

2. Off Study Use of t-PA [30 days or ICU discharge]

   off study use

3. Clinical Bleeding [30 days or ICU discharge]

   clinically significant bleeding

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53201

Sponsors and Collaborators

• Medical College of Wisconsin

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 5, 2019
• Informed Consent Form - Nov 20, 2019

More Information

Publications

None provided.

• Responsible Party: Sheila Hanson, Professor, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT03672006
• Other Study ID Numbers: MCWisconsin
• First Posted: Sep 14, 2018
• Last Update Posted: Jul 13, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Infections; Communicable Diseases; Sepsis; Thrombosis; Upper Extremity Deep Vein Thrombosis; Heparin; Tissue Plasminogen Activator

Study Results

Participant Flow

Arm/Group Title	Alteplase	Heparin
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	9
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Alteplase	Heparin	Total
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter	Total of all reporting groups
Overall Participants	10	9	19
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	5.5	3	3
Sex: Female, Male (Count of Participants)
Female	4 40%	3 33.3%	7 36.8%
Male	6 60%	6 66.7%	12 63.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	9 100%	19 100%
CVC type (Count of Participants)
Untunneled	7 70%	8 88.9%	15 78.9%
PICC	2 20%	1 11.1%	3 15.8%
Broviac/Hickman	1 10%	0 0%	1 5.3%

Outcome Measures

1. Primary Outcome

Title	Catheter-associated Venous Thrombosis
Description	Catheter-associated Venous Thrombosis upon ICU discharge or 30 days
Time Frame	30 days or ICU discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alteplase	Heparin
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter
Measure Participants	10	9
Count of Participants [Participants]	3 30%	3 33.3%

2. Primary Outcome

Title	Catheter-associated Bloodstream Infection
Description	CLABSI
Time Frame	30 days or ICU discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alteplase	Heparin
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter
Measure Participants	10	9
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Episodes of CVC Dysfunction
Description	Episodes of CVC dysfunction
Time Frame	30 days or ICU discharge

Outcome Measure Data

Analysis Population Description

episode of CVC dysfunction as inability to flush or draw

Arm/Group Title	Alteplase	Heparin
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter
Measure Participants	10	9
Number [episodes]	5	2

4. Secondary Outcome

Title	Off Study Use of t-PA
Description	off study use
Time Frame	30 days or ICU discharge

Outcome Measure Data

Analysis Population Description

number of episodes of off-study t-PA use

Arm/Group Title	Alteplase	Heparin
Arm/Group 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	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) Heparin: Medication administered to dwell in central venous catheter
Measure Participants	10	9
Median (Inter-Quartile Range) [doses]	0.5	0

5. Secondary Outcome

Title	Clinical Bleeding
Description	clinically significant bleeding
Time Frame	30 days or ICU discharge

Outcome Measure Data

Analysis Population Description

Bleeding events defined as clinically significant

Arm/Group Title	Alteplase	Heparin
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter	9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter
Measure Participants	10	9
Number [episodes]	0	0

Adverse Events

Time Frame	30 days after study completion
Adverse Event Reporting Description	clinical bleeding
Arm/Group Title	Alteplase		Heparin
Arm/Group Description	10 patients received 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) alteplase (recombinant t-PA): Medication administered to dwell in central venous catheter		9 patients received 30 min-4 hours heparin (10U/ml, up to 2 ml per dose) dwells to central venous catheter every 3 days (maximum 10 doses) Heparin: Medication administered to dwell in central venous catheter
All Cause Mortality
	Alteplase		Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)
Serious Adverse Events
	Alteplase		Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Alteplase		Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.