Pediatric Catheter-related Thrombosis Imaging Study (AESOP)

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

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

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Procedure: Ultrasound; Drug: Magnetic Resonance Imaging with Contrast; Procedure: Magnetic Resonance Imaging without Contrast

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Local Institution
  • Buenos Aires, Argentina, 1425
    • Local Institution
  • Buenos Aires, Argentina, 1270
    • Local Institution
• Austria
  • Vienna, Austria, A-1090
    • Local Institution
• Brazil
  • Sao Paulo, Brazil, 04023-062
    • Local Institution
  • Sao Paulo, Brazil, 05410
    • Local Institution
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Local Institution
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Local Institution
    • Toronto, Ontario, Canada, M5G 1X8
      • Local Institution
• Germany
  • Freiburg, Germany, 79106
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
• Mexico
  • Distrito Federal
    • Col. Secc Xvi Tlalpan, Distrito Federal, Mexico, 14080
      • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44260
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Local Institution
• United Kingdom
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G3 8SJ
      • Local Institution
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Missouri
    • Kansas City, Missouri, United States, 64108-4619
      • Children's Mercy Hospital and Clinics
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hopsital of Pittsburgh of UPMC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Dodson Specialty Clinics
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • Ut Health/Gulf States Hemophilia & Thrombophilia Ctr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort A: US, MRI with contrast, MRI without contrast; 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; Ultrasounds to be performed on children with central venous catheters; Other Names: US; Drug: Magnetic Resonance Imaging with Contrast; Contrast-enhanced Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters; Other Names: MRI with contrast; Procedure: Magnetic Resonance Imaging without Contrast; Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters; Other Names: MRI
Other: Cohort B: US, MRI with contrast, MRI without contrast; 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; Ultrasounds to be performed on children with central venous catheters; Other Names: US; Drug: Magnetic Resonance Imaging with Contrast; Contrast-enhanced Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters; Other Names: MRI with contrast; Procedure: Magnetic Resonance Imaging without Contrast; Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters; Other Names: MRI
Other: Cohort C: US, MRI with contrast, MRI without contrast; 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; Ultrasounds to be performed on children with central venous catheters; Other Names: US; Drug: Magnetic Resonance Imaging with Contrast; Contrast-enhanced Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters; Other Names: MRI with contrast; Procedure: Magnetic Resonance Imaging without Contrast; Magnetic Resonance Imaging (MRI) to be performed on children with central venous catheters; Other Names: MRI

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Pfizer

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: June 3, 2010
• First Submitted That Met QC Criteria: June 3, 2010
• First Posted (Estimate): June 4, 2010

Study Record Updates

• Last Update Posted (Estimate): December 15, 2014
• Last Update Submitted That Met QC Criteria: November 25, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: CV185-077; 2009-016906-18 (EudraCT Number)