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

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00633061
• Collaborator: (none)
• Enrollment: 136
• Location: 1
• Arms: 2
• Actual Duration (Months): 42
• Patients Per Site Per Month: 3.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Cancer; Central Venous Catheters; Deep Vein Thrombosis; Catheter-related Infection; Catheter-related Occlusion	Drug: Enoxaparin	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study on the Identification and Treatment of Clinically Silent Catheter-Related Deep Vein Thrombosis in Children With Cancer
• Actual Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A-randomized to treatment Patients diagnosed with asymptomatic catheter-related DVT who are randomized to treatment with enoxaparin for 6 weeks	Drug: 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.; Other Names: Lovenox
No Intervention: B-randomized to close Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation for 6 weeks

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Bleeding Complications Associated With Enoxaparin Therapy, Need for Additional Platelets [6 weeks]

   Bleeding complications associated with enoxaparin therapy, need for additional platelets

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Medical Center	Dallas	Texas	United States	75235

Sponsors and Collaborators

• University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Janna Journeycake, MD, University of Texas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00633061
• Other Study ID Numbers: K23HL084097; STU12207-062
• First Posted: Mar 11, 2008
• Last Update Posted: Oct 8, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by University of Texas Southwestern Medical Center: Childhood Cancer; Central Venous Catheter; Deep Vein Thrombosis; Catheter-related Infection; Catheter-related Occlusion
• Additional relevant MeSH terms: Catheter-Related Infections; Thrombosis; Venous Thrombosis; Enoxaparin

Study Results

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

Arm/Group Title	A-Prosepctive Screening for Asymptomatic DVT	B-Randomized Clinical Trail for Treatment
Arm/Group Description	Patients </=18 years of age with cancer and a first indwelling catheter expected to be in place for 3 months are enrolled. They are screened with either contrast venogram or ultrasound for asymptomatic catheter-related DVT if they have had at least 2 complications including line occlusion requiring tpa or catheter infection that did not result in removal of the line. If they have a positive screening study they are eligible for Arm B	Patients diagnosed with asymptomatic catheter-related DVT who are randomized to between enoxaparin or close observation for 6 weeks
Period Title: Overall Study
STARTED	136	0
Met Criteria for Imaging	25	0
Had Prior Thrombosis Identified	25	0
COMPLETED	50	0
NOT COMPLETED	86	0

Baseline Characteristics

Arm/Group Title	A-Prosepctive Screeing for Asymptomatic DVT	B-Randomized Clinical Trail for Treatment	Total
Arm/Group Description	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.	Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation for 6 weeks	Total of all reporting groups
Overall Participants	136	0	136
Age (Count of Participants)
<=18 years	136 100%	136 Infinity
Between 18 and 65 years	0 0%	0 NaN
>=65 years	0 0%	0 NaN
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	10	10
Sex: Female, Male (Count of Participants)
Female	69 50.7%	69 Infinity
Male	67 49.3%	67 Infinity
Region of Enrollment (participants) [Number]
United States	136 100%	136 Infinity

Outcome Measures

1. Primary Outcome

Title	Composite Endpoint for Arm B of the Study: Catheter Removal, Signs and Symptoms of DVT or PE, OR Bacteremia/Fungemia
Description	catheter removal, signs and symptoms of DVT or PE, OR bacteremia/fungemia
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

No patient was enrolled on the randomized clinical trial (arm B) after being on the prospective screening trial (Arm A)

Arm/Group Title	A- Prospective Screening for Asymptomatic Catheter-related DVT	B-Randomized Clinical Trail for Treatment
Arm/Group Description	Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation or treatment with enoxaparin
Measure Participants	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Since no patient was enrolled on Arm B of this study, there is no analysis of bleeding.

Arm/Group Title	A: Prospectvie Screening for Asymptomatic Catheter-related DVT	B-randomized Treatment Trail
Arm/Group Description	Patients </=18 years of age with cancer and a first indwelling catheter expected to be in place for 3 months are enrolled. They are screened with either contrast venogram or ultrasound for asymptomatic catheter-related DVT if they have had at least 2 complications including line occlusion requiring thrombolysis or catheter infection that did not result in removal of the line. If they have a positive screening study they are eligible for Arm B	Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation or enoxaparin to treat asymptomatic DVT
Measure Participants	0	0

Adverse Events

Arm/Group Title	A-Prospective Screening for Asymptomatic Catheter-related DVT		B-Randomized Clinical Trial
Arm/Group Description	Patients </=18 years of age with cancer and a first indwelling catheter expected to be in place for 3 months are enrolled. They are screened with either contrast venogram or ultrasound for asymptomatic catheter-related DVT if they have had at least 2 complications including line occlusion requiring thrombolysis or catheter infection that did not result in removal of the line. If they have a positive screening study they are eligible for Arm B		Patients diagnosed with asymptomatic catheter-related DVT who are randomized to close observation vs enoxaparin for 6 weeks
All Cause Mortality
	A-Prospective Screening for Asymptomatic Catheter-related DVT		B-Randomized Clinical Trial
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/136 (0%)		0/0 (NaN)
Serious Adverse Events
	A-Prospective Screening for Asymptomatic Catheter-related DVT		B-Randomized Clinical Trial
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/136 (11.8%)		0/0 (NaN)
Vascular disorders
Thrombosis	7/136 (5.1%)	7	0/0 (NaN)	7
removal of indwelling catheter for reasons other than end of therapy	9/136 (6.6%)	9	0/0 (NaN)	9
Other (Not Including Serious) Adverse Events
	A-Prospective Screening for Asymptomatic Catheter-related DVT		B-Randomized Clinical Trial
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/136 (0%)		0/0 (NaN)

Limitations/Caveats

Study terminated early for lack of accrual on Arm B (randomized trial). No patient enrolled on Arm A (screening study) were eligible. Standard treatment of asymptomatic catheter-related DVT changed in 2010, favoring treatment with enoxaparin.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.