Clinical trial NCT02355743: rtPA in in the Prevention of CVAD-Associated Thrombosis and Infection in Pediatric Patients With Short Bowel Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Short Bowel Syndrome
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
First posted: 2015-02-04
Enrollment: 8
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Development of CVAD Line Thrombosis
timeFrame: 24 weeks
Secondary outcomes:
measure: Development of Line-associated Infection
timeFrame: 24 weeks
measure: Need for Central Line Replacement
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Lynn Malec, MD
role: PRINCIPAL_INVESTIGATOR
References: