rtPA in in the Prevention of CVAD-Associated Thrombosis and Infection in Pediatric Patients With Short Bowel Syndrome

NCT ID: NCT02355743

Last Updated: 2018-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-01
• Study Completion Date: 2016-09-03

Brief Summary

The primary research question is, in patients with short bowel syndrome requiring central venous access device (CVAD) for long-term total parenteral nutrition, is once weekly recombinant tissue plasminogen activator (rtPA) lock therapy more effective than routine care using heparin flushes in reducing the incidence of line-associated thrombosis and infection.

Detailed Description

Central venous access devices (CVAD) are used routinely in chronically ill pediatric patients for administration of medications, parenteral nutrition and laboratory testing. Several complications resulting from the use of long-term CVADs, namely venous sepsis and thrombosis, can significantly increase associated morbidity and mortality. CVAD-associated thrombosis occurs in up to 50% of children with long-term CVAD use and this is especially common in patients requiring life-sustaining long-term total parenteral nutrition (1). Catheter thrombosis may arise from fibrin sheath formation around the catheter tip, intraluminal blood clot within the catheter, or venous thrombosis obstructing the vein and occluding the catheter tip. Within 24 hours and typically within 2 weeks of placement of a CVAD, a fibrin sheath forms around its tip (2-5). Development of intraluminal thrombosis or venous thrombosis is less predictable.

There is a growing body of evidence linking the development of CVAD-associated thrombosis and line-related infection. It is known that proteins within the thrombus including fibronectin and fibrinogen attract bacteria, specifically staphylococcal species. The bacteria bind to ligands associated with the thrombus thus allowing for bacterial proliferation (6-8). The clinical relevance of line thrombus in development of line infection is underscored in a study of pediatric patients with Hickman catheters, of whom 18% with catheter thrombosis developed a line-associated bloodstream infection, while none developed a catheter infection that did not also have a catheter clot (7). Thus, we hypothesize that prevention of catheter-related clot formation with use of a local thrombolytic agent will also prevent infection in the catheter.

The primary research question we pose is, in patients with short bowel syndrome requiring central venous access device (CVAD) for long-term total parenteral nutrition, is once weekly recombinant tissue plasminogen activator (rtPA) lock therapy more effective than routine care using heparin flushes in reducing the incidence of line-associated thrombosis and infection.

Conditions

Short Bowel Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

rtPA lock therapy Recipients

rtPA 2 mg/2 ml, or 110% of the volume of the catheter lumen if less than 2 mL, administered locally in a volume to fill the lumen (dead space) of the CVAD, once weekly for a total of 24 weeks

Group Type: EXPERIMENTAL

rtPA lock therapy

Intervention Type: DRUG

rtPA 2 mg/2 ml, or 110% of the volume of the catheter lumen if less than 2 mL, administered locally in a volume to fill the lumen (dead space) of the CVAD, once weekly for a total of 24 weeks. rtPA will be given as research intervention as "lock therapy" in that it will dwell within the catheter of the CVAD for a specified duration of time and then be removed (aspirated); in this setting the medication is not given to the patient as a flush, i.e. in systemic fashion.

Interventions

rtPA lock therapy

rtPA 2 mg/2 ml, or 110% of the volume of the catheter lumen if less than 2 mL, administered locally in a volume to fill the lumen (dead space) of the CVAD, once weekly for a total of 24 weeks. rtPA will be given as research intervention as "lock therapy" in that it will dwell within the catheter of the CVAD for a specified duration of time and then be removed (aspirated); in this setting the medication is not given to the patient as a flush, i.e. in systemic fashion.

Intervention Type: DRUG

Other Intervention Names

rtPA

Eligibility Criteria

Inclusion Criteria

1. subjects with short bowel syndrome

2. requirement for central venous access device (CVAD) for long-term TPN administration

3. age >/= 6 months to < 16 years

4. ability to initiate rtPA during hospitalization for newly inserted CVAD

5. ability to be enrolled within 48 hours of CVAD placement.

Exclusion Criteria

1. platelet count <50,000

2. active bleeding

3. age =/> 16 years at time of consent.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Lynn Malec

OTHER

Sponsor Role: lead

Responsible Party

Lynn Malec

Assistant Professor of Medicine and Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lynn Malec, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

PRO13120030

Identifier Type: -

Identifier Source: org_study_id