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

Short Bowel Syndrome Clinical Trial

Official title:

Prophylactic Recombinant Tissue Plasminogen Activator in the Prevention of Central Venous Access Device (CVAD)-Associated Thrombosis and Infection in Pediatric Patients With Short Bowel Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02355743
• Other study ID #: PRO13120030
• Status: Completed
• Phase: Phase 4
• First received: January 30, 2015
• Last updated: January 8, 2018
• Start date: February 1, 2015
• Est. completion date: September 3, 2016

Study information

• Verified date: January 2018
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 3, 2016
• Est. primary completion date: September 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome
• Thrombosis

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Lynn Malec	University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of CVAD Line Thrombosis	This will be defined as a thrombosis that is discovered due to clinical findings concerning for a possible thrombosis as identified by the treating physician including, but not limited to, swelling, color change, or pain in the extremity, CVAD not providing blood return and/or being able to be flushed.	24 weeks
Secondary	Development of Line-associated Infection	This will be defined as a line associated infection not related to other co-infection (i.e. such as pneumonia, UTI)	24 weeks
Secondary	Need for Central Line Replacement	This will be defined as a line removal and replacement due to infection, malfunction or other issues	24 weeks