rtPA in in the Prevention of CVAD-Associated Thrombosis and Infection in Pediatric Patients With Short Bowel Syndrome
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Thrombosis; Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): rtPA lock therapy
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): rtPA
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention