Identification and Treatment of Clinically Silent Catheter-Related Deep Vein Thrombosis in Children With Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study on the Identification and Treatment of Clinically Silent Catheter-Related Deep Vein Thrombosis in Children With Cancer

Conditions
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Childhood Cancer, Central Venous Catheters, Deep Vein Thrombosis, Catheter-related Infection, Catheter-related Occlusion

Intervention / Treatment
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* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cancer Age ≤ 18 years 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 Catheter expected to be in place for duration of chemotherapy (≥ 3 months) History of no more than one catheter complication (occlusion or infection) Exclusion Criteria: Prior history of DVT Currently receiving an anticoagulant or anti-platelet agents on a daily basis Diagnosis of high grade malignant brain tumor or metastasis to the brain Clinical signs/symptoms of DVT Clinical signs/symptoms of Pulmonary embolism Renal failure Recent major hemorrhage

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A-randomized to treatment<br>Patients diagnosed with asymptomatic catheter-related DVT who are randomized to treatment with enoxaparin for 6 weeks | Drug: Enoxaparin<br>* 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.<br>* Other names: Lovenox;|
| No Intervention: B-randomized to close<br>Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation for 6 weeks | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Complications Associated With Enoxaparin Therapy, Need for Additional Platelets | Bleeding complications associated with enoxaparin therapy, need for additional platelets | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Childhood Cancer, Central Venous Catheter, Deep Vein Thrombosis, Catheter-related Infection, Catheter-related Occlusion