Catheter-related Infection, Catheter-related Occlusion, Central Venous Catheters, Childhood Cancer, Deep Vein Thrombosis
Conditions
Keywords
Childhood Cancer, Central Venous Catheter, Deep Vein Thrombosis, Catheter-related Infection, Catheter-related Occlusion
Brief summary
The primary hypothesis of this study is that occult catheter-related DVT in children with cancer is common and directly contributes to development of serious catheter complications, specifically bacteremia/fungemia and/or recurrent occlusion of the catheter tip. Accordingly, anticoagulant treatment of clinically silent (occult) DVT will reduce rates of catheter-related infection and occlusion, delays in therapy and need for catheter replacement.
Detailed description
This is a two-part study with an initial diagnosis component followed by a treatment component. The number of subjects to be consented for the diagnosis component is 350, and 50 for the treatment portion (25 on the observation arm, and 25 for enoxaparin treatment). Study Procedures: Patients diagnosed with cancer at the Center for Cancer and Blood Disorders will have a catheter inserted for cancer related treatment. After insertion, eligible patients who provide consent will be enrolled in the diagnosis component of the study. The principal investigator and research team will monitor for catheter complications (occlusion and bacteremia/fungemia). After two complications, participants will be screened for occult central venous catheter (CVC)-related DVT by contrast venography, ultrasonography, or magnetic resonance venography. If DVT is not diagnosed, participant will go off the study. If DVT is diagnosed, participant will be asked to consent to enroll in the treatment study. After enrollment, participant is randomized between the two arms of observation and enoxaparin treatment. After 6 weeks, patients will have another image; this represents the end of treatment period. After the follow-up imaging, patients will be monitored for 10 weeks to obtain primary outcomes. Once a primary outcome (progression to symptomatic DVT or pulmonary embolism (PE), blood stream infection or catheter removal) is achieved the participants can be treated with anticoagulation again if necessary, but primary oncologist will determine treatment. Analysis: The hypothesis is that the enoxaparin treatment group will have a median adverse catheter event free survival time of 12 weeks versus 4 weeks for the control group with a hazard ration of 0.4. A total sample size of 50 (25 in each arm) will detect such a difference with 90% power at an α=0.05. If there is a drop out rate of 10% in each arm, a difference can still be detected with 80% power. Approximately 200 to 250 patients are diagnosed with cancer each year at Children's Medical Center Dallas, and based on prior institutional experience, two-thirds will have catheters inserted to facilitate chemotherapy. However, one-quarter of these patients have brain tumors and are not eligible due to the potential increased risk of intracranial hemorrhage with anticoagulation. There will be 100 patients each year who are at risk for CVC-related DVT. Based on previous studies, up to 50% of patients should develop occult DVT; however, only 35% of patients will likely be screened with radiographic imaging. Approximately 17 patients a year enrolled in the diagnosis study may be diagnosed with DVT and eligible for randomization. Therefore, total enrollment will be completed in approximately 3 years with an additional 4 months necessary to complete the follow-up period.
Interventions
DRUGEnoxaparin
Lovenox ® is a sterile aqueous solution containing enoxaparin sodium, a low molecular weight heparin. It is given as a subcutaneous injection twice daily. Dose of enoxaparin (Lovenox ®) will be 1 mg/kg every 12 hours for children \>2 months and 1.5 mg/kg every 12 hours for infants \<2 months. Duration of treatment is 6 weeks.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of cancer 2. Age ≤ 18 years 3. First tunneled central venous catheter (implanted port or external) inserted in the upper venous system (subclavian, brachiocephalic, or jugular vein) within the previous 2 weeks 4. Catheter expected to be in place for duration of chemotherapy (≥ 3 months) 5. History of no more than one catheter complication (occlusion or infection)
Exclusion criteria
1. Prior history of DVT 2. Currently receiving an anticoagulant or anti-platelet agents on a daily basis 3. Diagnosis of high grade malignant brain tumor or metastasis to the brain 4. Clinical signs/symptoms of DVT 5. Clinical signs/symptoms of Pulmonary embolism 6. Renal failure 7. Recent major hemorrhage
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint for Arm B of the Study: Catheter Removal, Signs and Symptoms of DVT or PE, OR Bacteremia/Fungemia | 16 weeks | catheter removal, signs and symptoms of DVT or PE, OR bacteremia/fungemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Complications Associated With Enoxaparin Therapy, Need for Additional Platelets | 6 weeks | Bleeding complications associated with enoxaparin therapy, need for additional platelets |
Countries
United States
Participant flow
Recruitment details
Recruitment from June 2008 to December 2010. For arm A, we screened 486 children and enrolled 136. 68 patients were eligible and not enrolled and 282 were ineligible. No patient was eligible for Arm B of this study
Participants by arm
| Arm | Count |
|---|---|
| A-Prosepctive Screeing for Asymptomatic DVT Patients diagnosed with asymptomatic catheter-related DVT who are randomized to treatment with enoxaparin for 6 weeks
Enoxaparin: Lovenox ® is a sterile aqueous solution containing enoxaparin sodium, a low molecular weight heparin. It is given as a subcutaneous injection twice daily. Dose of enoxaparin (Lovenox ®) will be 1 mg/kg every 12 hours for children \>2 months and 1.5 mg/kg every 12 hours for infants \<2 months. Duration of treatment is 6 weeks. | 136 |
| B-Randomized Clinical Trail for Treatment Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation for 6 weeks | 0 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study closed | 86 | 0 |
Baseline characteristics
| Characteristic | Total | A-Prosepctive Screeing for Asymptomatic DVT |
|---|---|---|
| Age, Categorical <=18 years | 136 Participants | 136 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Age, Continuous | 10 years | 10 years |
| Region of Enrollment United States | 136 participants | 136 participants |
| Sex: Female, Male Female | 69 Participants | 69 Participants |
| Sex: Female, Male Male | 67 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 136 | 0 / 0 |
| other Total, other adverse events | 0 / 136 | 0 / 0 |
| serious Total, serious adverse events | 16 / 136 | 0 / 0 |
Outcome results
Primary
Composite Endpoint for Arm B of the Study: Catheter Removal, Signs and Symptoms of DVT or PE, OR Bacteremia/Fungemia
catheter removal, signs and symptoms of DVT or PE, OR bacteremia/fungemia
Time frame: 16 weeks
Population: No patient was enrolled on the randomized clinical trial (arm B) after being on the prospective screening trial (Arm A)
Secondary
Bleeding Complications Associated With Enoxaparin Therapy, Need for Additional Platelets
Bleeding complications associated with enoxaparin therapy, need for additional platelets
Time frame: 6 weeks
Population: Since no patient was enrolled on Arm B of this study, there is no analysis of bleeding.