Pediatric Catheter-related Thrombosis Imaging Study

Study Overview
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Brief Summary
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This protocol will serve as a pilot study to determine the validity and feasibility of contrast enhanced magnetic resonance imaging (MRI) without and with contrast and/or ultrasound (US) for detection of catheter related deep vein thrombosis (DVT) in children

Official Title
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Pilot Study for Assessing Diagnostic Techniques for Central Venous Catheter-related Venous Thromboembolism

Conditions
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Thrombosis

Intervention / Treatment
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* Procedure: Ultrasound
* Drug: Magnetic Resonance Imaging with Contrast
* Procedure: Magnetic Resonance Imaging without Contrast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Functioning central venous catheter in the upper or lower venous system Cohort A: Asymptomatic patients having placement of a new central venous catheter in the last 40±20 days Cohort B: Subjects who have experienced symptoms for a CVC-related DVT with a CVC in place or subjects who have been incidentally identified by radiographic imaging (imaging modalities to diagnose an incidental CVC-related DVT may include, but is not exclusive of Echocardiogram, CT scan, MRI, or Ultrasound) performed for other clinical reasons, as having a CVC-related DVT in the veins where the current catheter is placed Males and females from full-term newborns to < 18 years Exclusion Criteria: For Cohort A subjects only, present therapeutic dosing of a systematic anticoagulant, systemic thromboprophylaxis or antiplatelet therapy. Local thromboprophylaxis [flushes, low dose infusions of heparin of up to 5 u/kg/hr or locks with heparin, urokinase, t-plasminogen activator] according to standard-of-care at the respective center will be allowed Patients unable to undergo contrast enhanced magnetic resonance imaging Renal function < 50% of normal for age and size

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort A: US, MRI with contrast, MRI without contrast<br>Subjects with a central venous catheter (CVC) in place and asymptomatic for a CVC-related DVT to have an Ultrasound (US), Magnetic Resonance Imaging (MRI) with contrast and MRI without contrast performed. | Procedure: Ultrasound<br>* Ultrasounds to be performed on children with central venous catheters<br>* Other names: US;Drug: Magnetic Resonance Imaging with Contrast<br>* Contrast-enhanced Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters<br>* Other names: MRI with contrast;Procedure: Magnetic Resonance Imaging without Contrast<br>* Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters<br>* Other names: MRI;|
| Other: Cohort B: US, MRI with contrast, MRI without contrast<br>Subjects with a CVC in place either symptomatic for a CVC-related DVT or having an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons to have an Ultrasound, Magnetic Resonance Imaging (MRI) with contrast and MRI without contrast performed. | Procedure: Ultrasound<br>* Ultrasounds to be performed on children with central venous catheters<br>* Other names: US;Drug: Magnetic Resonance Imaging with Contrast<br>* Contrast-enhanced Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters<br>* Other names: MRI with contrast;Procedure: Magnetic Resonance Imaging without Contrast<br>* Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters<br>* Other names: MRI;|
| Other: Cohort C: US, MRI with contrast, MRI without contrast<br>Subjects with a CVC in place having an MRI for clinical reasons to have an Ultrasound, Magnetic Resonance Imaging (MRI) with contrast and MRI without contrast performed. | Procedure: Ultrasound<br>* Ultrasounds to be performed on children with central venous catheters<br>* Other names: US;Drug: Magnetic Resonance Imaging with Contrast<br>* Contrast-enhanced Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters<br>* Other names: MRI with contrast;Procedure: Magnetic Resonance Imaging without Contrast<br>* Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters<br>* Other names: MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Participants Who Completed the Study-Related Ultrasound (US) and Magnetic Resonance Imaging (MRI) With and Without Contrast | One set of 3 diagnostic imaging procedures (US, MRI with contrast, and MRI without contrast) was performed for all cohorts. Imaging was performed on Visit 1, which in Cohort A was Day 40 ± 20 days from Day 0, the placement of the central venous catheter (CVC), or if possible within 72 hours after a CVC was removed or lost; Visit 1 in Cohort B was within 7 days of initiation of symptoms of a CVC-related deep vein thromboembolism (DVT) or within 7 days of an incidental diagnosis of CVC-related DVT by radiographic imaging. Cohort C participants had an ultrasound done within 48 hours of the performance of the MRI, which was scheduled for a clinical reason. Note: participants completing each MRI procedure (with contrast or without contrast) could be different participants. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C). | 
| Number of Participants Who Completed the Study-Related Ultrasound and Magnetic Resonance Imaging (MRI) With and Without Contrast, by Cohort and Age Group | Imaging was performed on Visit 1 which was defined for Cohort A as: Day 40 ± 20 days from Day 0, the placement of the central venous catheter (CVC), or if possible within 72 hours after a CVC was removed or lost; Visit 1 defined for Cohort B: within 7 days of initiation of symptoms of a CVC-related deep vein thromboembolism (DVT) or within 7 days of an incidental diagnosis of CVC-related DVT by radiographic imaging. Cohort C participants had an ultrasound done within 48 hours of the performance of the MRI. All 3 imaging procedures, ultrasound, MRI with contrast, MRI without contrast were to be performed on all participants, regardless of the cohort. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C) | 
| Number of Participants Who Required Sedation/Anesthesia With the Study-Related Radiographic Procedures, by Cohort and Age | One set of diagnostic imaging procedures (US and MRI) was to be performed for all cohorts The MRI consisted of MRI venous imaging without contrast enhancement and MRI venous imaging with contrast enhancement. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C). | 
| Number of Participants and Reasons for Non-Completion of Each of the Imaging Procedures, Ultrasound (US), MRI With Contrast and MRI Without Contrast | Bilateral US was attempted but if it could not be completed, a unilateral US was accepted for analysis. Participants who did not complete the MRI procedure with contrast could be different participants from those who did not complete the MRI procedure without contrast. Primary reasons for non-completion of imaging included: technical, investigator decision, child refused, parent refused, child missed appointment, difficulties with anesthesia/sedation, child unable to lie still, problems with contrast administration, and other reasons. Other reasons could include: late to appointment and unable to perform MRI due to time constraints; logistical reasons, parent agreed to only ultrasound at time of consent, schedule delay, equipment not available, difficulty putting patient in correct position. Due to the small numbers of participants in some cohorts, these data were more meaningful with all cohorts grouped together for the total imaged population. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C). | 
| Number of Participants With an Adjudicated Deep Vein Thrombosis (DVT) Detected By a Study-Related Ultrasound (US) and/or MRI, By Cohort and Age Group | MRI with contrast (c) and without (w/o) contrast (c) enhancement were performed and a US was done within 48 hours of the MRI. Once detected, the DVT was adjudicated and confirmed by an independent central adjudication Committee (ICAC) consisting of experienced physicians not involved in the study and blinded to each participant's identity and clinical course. Participants were considered positive for DVT if at least one of the radiographic procedures was positive. Cohort A: Day 0=day of catheter placement; Day 40 (± 20 days)=day of imaging procedures at Visit 1, or if possible within 72 hours after a CVC is removed or lost. Cohort B Visit 1: within 7 days of initiation of symptoms of a CVC-related DVT (symptoms include but were not limited to: redness, pain/tenderness, swelling, presence of subcutaneous collaterals, catheter occlusion, and the presence of catheter related infection) or within 7 days of an incidental diagnosis of CVC-related DVT by radiographic imaging. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C) | 
| All Participants With an Adjudicated Deep Vein Thromboembolism (DVT) By Study-Related Radiographic Procedures That Diagnosed the DVT | Adjudication was by an Independent Central Adjudication Committee (ICAC) consisting of experienced physicians not involved in the study and blinded to each participant's identity and clinical course. One set of 3 study-related diagnostic imaging procedures (US, MRI with contrast, and MRI without contrast) was performed. Participants were considered positive for DVT if at least one of the radiographic procedures was positive. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of All Participants Identified With Adjudicated DVT Categorized By Presence or Absence of Symptoms at Enrollment | Adjudication was by an ICAC consisting of experienced physicians not involved in the study and blinded to each participant's identity and clinical course. One set of Study-related diagnostic imaging procedures (US, MRI with contrast, and MRI without contrast) was performed for all cohorts. Participants were considered positive for DVT if at least one of the radiographic procedures was positive. | Either Day 40±20 days following the placement of CVC (cohort A) or within 7 days of: symptoms of DVT or incidental diagnosis of CVC-related DVT(cohort B) or Day of MRI + 48 hours (cohort C) | 
| Number of Participants With Adjudicated Pulmonary Embolism (PE) Events (Symptomatic or Asymptomatic) Identified During the Study | Signs and symptoms of PE include shortness of breath, pleuritic pain, cough, orthopnea, wheezing, and may have associated signs and symptoms of DVT. In the event a PE was detected while undergoing the study MRI or other imaging procedure required for care of an underlying condition, and the participant did not manifest any signs and/or symptoms of a PE, the event was considered an asymptomatic PE. The participant was managed and further investigated according to the investigator's standard of care. All diagnostic imaging procedures performed, such as contrast-enhanced computer tomography (CT) pulmonary angiogram, nuclear ventilation perfusion lung scan (V/Q scan), were submitted for adjudication as a suspected PE. | Enrollment up to Visit 1 plus 30 days (up to approximately 90 days) | 
| Number of Deaths Which Occurred During the Study | Death as an endpoint in a participant with an adjudicated venous thromboembolism (DVT or PE) was summarized, regardless of the cause of the death. The VTE was adjudicated by a blinded central independent adjudication committee. | Enrollment up to last US or MRI plus 30 days (up to approximately 90 days) |