Clinical trial NCT00633061: Identification and Treatment of Clinically Silent Catheter-Related Deep Vein Thrombosis in Children With Cancer
Official title: Phase II Study on the Identification and Treatment of Clinically Silent Catheter-Related Deep Vein Thrombosis in Children With Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Childhood Cancer
Central Venous Catheters
Deep Vein Thrombosis
Catheter-related Infection
Catheter-related Occlusion
Keywords: Childhood Cancer
Central Venous Catheter
Deep Vein Thrombosis
Catheter-related Infection
Catheter-related Occlusion
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2008-03-11
Enrollment: 136
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite Endpoint for Arm B of the Study: Catheter Removal, Signs and Symptoms of DVT or PE, OR Bacteremia/Fungemia
timeFrame: 16 weeks
Secondary outcomes:
measure: Bleeding Complications Associated With Enoxaparin Therapy, Need for Additional Platelets
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
Study officials:
affiliation: University of Texas
name: Janna Journeycake, MD
role: PRINCIPAL_INVESTIGATOR
References: