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

Lynn Malec

Status and phase: Completed; Phase 4

Conditions: Short Bowel Syndrome

Treatments: Drug: rtPA lock therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02355743

PRO13120030

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 6 months to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

rtPA lock therapy Recipients

Experimental group

Description:

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

Treatment:

Drug: rtPA lock therapy