Short Bowel Syndrome
Conditions
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.
Interventions
DRUGrtPA 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.
Sponsors
University of Pittsburgh
Lynn Malec
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of CVAD Line Thrombosis | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Development of Line-associated Infection | 24 weeks | This will be defined as a line associated infection not related to other co-infection (i.e. such as pneumonia, UTI) |
| Need for Central Line Replacement | 24 weeks | This will be defined as a line removal and replacement due to infection, malfunction or other issues |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the Children's Hospital of Pittsburgh of UPMC inpatient setting
Pre-assignment details
All patients received study intervention of rtPA lock therapy which was initiated within 48 hours of a new central venous access device being placed.
Participants by arm
| Arm | Count |
|---|---|
| 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
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. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | rtPA Lock Therapy Recipients |
|---|---|
| Age, Continuous | 4.4 years |
| Central venous access device associated infections in prior 6 months | 2 infections |
| Central venous access devices in prior 6 months | 2 central venous access devices |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hospitalizations in prior 6 months | 3 hospitalizations |
| Lifetime number of central venous access devices | 6.5 central venous access devices |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
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.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rtPA Lock Therapy Recipients | Development of CVAD Line Thrombosis | 0 thromboses |
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)
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| rtPA Lock Therapy Recipients | Development of Line-associated Infection | 0.5 infections |
Secondary
Need for Central Line Replacement
This will be defined as a line removal and replacement due to infection, malfunction or other issues
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| rtPA Lock Therapy Recipients | Need for Central Line Replacement | 1 line replacements |