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

NCT ID: NCT00633061

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2011-12-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A-randomized to treatment

Patients diagnosed with asymptomatic catheter-related DVT who are randomized to treatment with enoxaparin for 6 weeks

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

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.

B-randomized to close

Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation for 6 weeks

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Lovenox

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janna Journeycake, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

Children's Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

STU12207-062

Identifier Type: OTHER

Identifier Source: secondary_id

K23HL084097

Identifier Type: NIH

Identifier Source: org_study_id

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