AESOP: Pediatric Catheter-related Thrombosis Imaging Study

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01137578
• Collaborator: Pfizer (Industry)
• Enrollment: 151
• Locations: 26
• Arms: 3
• Duration (Months): 26.9
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Thrombosis	Procedure: Ultrasound; Drug: Magnetic Resonance Imaging with Contrast; Procedure: Magnetic Resonance Imaging without Contrast	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Pilot Study for Assessing Diagnostic Techniques for Central Venous Catheter-related Venous Thromboembolism
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Total Number of Participants Who Completed the Study-Related Ultrasound (US) and Magnetic Resonance Imaging (MRI) With and Without Contrast [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).]

   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.

2. Number of Participants Who Completed the Study-Related Ultrasound and Magnetic Resonance Imaging (MRI) With and Without Contrast, by Cohort and Age Group [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)]

   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.

3. Number of Participants Who Required Sedation/Anesthesia With the Study-Related Radiographic Procedures, by Cohort and Age [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).]

   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.

4. Number of Participants and Reasons for Non-Completion of Each of the Imaging Procedures, Ultrasound (US), MRI With Contrast and MRI Without Contrast [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).]

   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.

5. 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 [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)]

   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.

6. All Participants With an Adjudicated Deep Vein Thromboembolism (DVT) By Study-Related Radiographic Procedures That Diagnosed the DVT [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)]

   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.

Secondary Outcome Measures

1. Number of All Participants Identified With Adjudicated DVT Categorized By Presence or Absence of Symptoms at Enrollment [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)]

   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.

2. Number of Participants With Adjudicated Pulmonary Embolism (PE) Events (Symptomatic or Asymptomatic) Identified During the Study [Enrollment up to Visit 1 plus 30 days (up to approximately 90 days)]

   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.

3. Number of Deaths Which Occurred During the Study [Enrollment up to last US or MRI plus 30 days (up to approximately 90 days)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children'S Hospital	Little Rock	Arkansas	United States	72202
2	University Of Colorado Denver	Aurora	Colorado	United States	80045
3	Children'S Mercy Hospital And Clinics	Kansas City	Missouri	United States	64108-4619
4	Akron Children'S Hospital	Akron	Ohio	United States	44308
5	Cincinnati Children'S Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
6	The Children'S Hospital Of Philadelphia	Philadelphia	Pennsylvania	United States	19104
7	Children'S Hopsital Of Pittsburgh Of Upmc	Pittsburgh	Pennsylvania	United States	15224
8	Dodson Specialty Clinics	Fort Worth	Texas	United States	76104
9	Texas Children'S Hospital	Houston	Texas	United States	77030
10	Ut Health/Gulf States Hemophilia & Thrombophilia Ctr.	Houston	Texas	United States	77030
11	Local Institution	Buenos Aires		Argentina	1270
12	Local Institution	Buenos Aires		Argentina	1425
13	Local Institution	Buenos Aires		Argentina	C1181ACH
14	Local Institution	Vienna		Austria	A-1090
15	Local Institution	Sao Paulo		Brazil	04023-062
16	Local Institution	Sao Paulo		Brazil	05410
17	Local Institution	Edmonton	Alberta	Canada	T6G 1C9
18	Local Institution	Ottawa	Ontario	Canada	K1H 8L1
19	Local Institution	Toronto	Ontario	Canada	M5G 1X8
20	Local Institution	Freiburg		Germany	79106
21	Local Institution	Hannover		Germany	30625
22	Local Institution	Col. Secc Xvi Tlalpan	Distrito Federal	Mexico	14080
23	Local Institution	Guadalajara	Jalisco	Mexico	44260
24	Local Institution	Monterrey	Nuevo Leon	Mexico	64460
25	Local Institution	Amsterdam		Netherlands	1105 AZ
26	Local Institution	Glasgow	Lanarkshire	United Kingdom	G3 8SJ

Sponsors and Collaborators

• Bristol-Myers Squibb
• Pfizer

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01137578
• Other Study ID Numbers: CV185-077; 2009-016906-18
• First Posted: Jun 4, 2010
• Last Update Posted: Dec 15, 2014
• Last Verified: Nov 1, 2014

• Additional relevant MeSH terms: Thrombosis

Study Results

Participant Flow

Recruitment Details	Study initiated: 28 February 2011; Study Completed: 10 May 2013. Patients with central venous catheter (CVC) in-place or planned were enrolled. The Study was diagnostic for venous thromboembolism (VTE) and was non-therapeutic.
Pre-assignment Detail	151 participants enrolled; 134 had at least one study-related diagnostic imaging procedure completed or partially completed; 17 enrolled but not identified to a cohort and no study-related imaging procedures performed: Adverse event (2), withdrew consent (1), lost to follow up (1), poor/non-compliance (1), no longer met criteria (3), other (9).

Arm/Group Title	Cohort A	Cohort B	Sub-Study Cohort C
Arm/Group Description	Cohort A included pediatric participants (full-term newborns to <18 years) in which a CVC was recently placed and who were asymptomatic for CVC-related deep vein thrombosis (DVT). Imaging procedures occurred on Day 40 ± 20 days relative to catheter placement (Day 0) and included: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used for MRI with contrast. No sedation or anesthesia was to be allowed. Participants who developed symptoms of VTE prior to imaging should have been switched to Cohort B.	Cohort B included pediatric participants (full-term newborns to <18 years) with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT based on radiographic imaging performed for other clinical reasons. Diagnostic imaging procedures, US and MRI (with and without gadolinium contrast enhancement) were to be done within 48 hours of each other or, for those with therapeutic anticoagulation, within 24 hours. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT.	A Sub-study with additional cohort C was initiated to collect diagnostic imaging procedures for the detection of CVC-related DVT in a population < 18 years of age who had a CVC in place and who were scheduled to undergo a contrast enhanced MRI in any part of their body as part of their clinical care and who allowed the diagnostic imaging procedure to include the area around the CVC. Participants who developed symptoms of VTE prior to imaging should have been switched to Cohort B.
Period Title: Overall Study
STARTED	77	14	43
COMPLETED	61	12	37
NOT COMPLETED	16	2	6

Baseline Characteristics

Arm/Group Title	All Imaged Participants
Arm/Group Description	Baseline parameters for all participants in Cohorts A, B, and C: Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed or who had a CVC in place. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related deep vein thrombosis (DVT) or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).
Overall Participants	134
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.9 (4.89)
Age, Customized (participants) [Number]
Less than (<) 2 years	7 5.2%
Between 2 years and <12 years	64 47.8%
Between 12 years and <18 years	63 47%
Sex: Female, Male (Count of Participants)
Female	56 41.8%
Male	78 58.2%
Race/Ethnicity, Customized (participants) [Number]
White	117 87.3%
Black/African American	7 5.2%
Asian	3 2.2%
American Indian or Alaska native	3 2.2%
Other	4 3%

Outcome Measures

1. Primary Outcome

Title	Total Number of Participants Who Completed the Study-Related Ultrasound (US) and Magnetic Resonance Imaging (MRI) With and Without Contrast
Description	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.
Time Frame	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).

Outcome Measure Data

Analysis Population Description

The imaged population included all enrolled participants who had at least 1 study-related diagnostic imaging procedure.

Arm/Group Title	All Imaged Participants
Arm/Group Description	All participants in Cohorts A, B, and C who had at least 1 radiographic procedure: Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed or who had a CVC in place. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related deep vein thrombosis (DVT) or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).
Measure Participants	134
Completed Ultrasound	133 99.3%
Completed the MRI with Contrast	113 84.3%
Completed the MRI without Contrast	113 84.3%
Completed All 3 Imaging Procedures	110 82.1%

2. Primary Outcome

Title	Number of Participants Who Completed the Study-Related Ultrasound and Magnetic Resonance Imaging (MRI) With and Without Contrast, by Cohort and Age Group
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The imaged population included all enrolled participants who had at least 1 study-related diagnostic imaging procedure.

Arm/Group Title	Cohort A Newborn to <2Years	Cohort A 2Years to <12Years	Cohort A 12Years to <18Years	Cohort B Newborn to <2Years	Cohort B 2Years to <12Years	Cohort B 12Years to <18Years	Cohort C Newborn to <2Years	Cohort C 2Years to <12Years	Cohort C 12Years to <18Years
Arm/Group Description	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.
Measure Participants	2	30	45	1	6	7	4	28	11
Only Ultrasound Completed	1 0.7%	7 NaN	6 NaN	0 NaN	1 NaN	0 NaN	1 NaN	3 NaN	0 NaN
Only MRI with contrast Completed	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Only MRI without contrast Completed	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
US and MRI with contrast Completed	0 0%	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN
US and MRI without contrast Completed	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
MRI with and without contrast Completed	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN
All 3 Imaging Procedures Completed	1 0.7%	22 NaN	38 NaN	1 NaN	5 NaN	6 NaN	3 NaN	24 NaN	10 NaN

3. Secondary Outcome

Title	Number of All Participants Identified With Adjudicated DVT Categorized By Presence or Absence of Symptoms at Enrollment
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

All participants who had an adjudicated DVT identified by at lest one study-related radiographic procedure.

Arm/Group Title	All Imaged Participants
Arm/Group Description	All participants in Cohorts A, B, and C who had at least 1 radiographic procedure: Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed or who had a CVC in place. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related deep vein thrombosis (DVT) or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).
Measure Participants	22
Symptoms at Enrollment; Adjudicated DVT	8 6%
Asymptomatic at Enrollment, Adjudicated DVT	14 10.4%

4. Secondary Outcome

Title	Number of Participants With Adjudicated Pulmonary Embolism (PE) Events (Symptomatic or Asymptomatic) Identified During the Study
Description	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.
Time Frame	Enrollment up to Visit 1 plus 30 days (up to approximately 90 days)

Outcome Measure Data

Analysis Population Description

The imaged population included all enrolled participants who had at least one study-related diagnostic imaging procedure.

Arm/Group Title	Cohort A	Cohort B	Cohort C
Arm/Group Description	Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia to be allowed. Participants enrolled in Cohort A and who developed symptoms of a venous thromboembolism (VTE), including a symptomatic DVT or a symptomatic pulmonary embolism (PE) prior to their MRI/US, were switched to Cohort B.	Pediatric Participants (full-term newborns to <18 years) with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Participants with a CVC in place and having an MRI for clinical reasons were enrolled.
Measure Participants	77	14	43
Number [participants]	0 0%	0 NaN	0 NaN

5. Primary Outcome

Title	Number of Participants Who Required Sedation/Anesthesia With the Study-Related Radiographic Procedures, by Cohort and Age
Description	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.
Time Frame	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).

Outcome Measure Data

Analysis Population Description

The imaged population included all participants who had at least 1 study-related diagnostic imaging procedure.

Arm/Group Title	Cohort A Participants <12Years of Age	Cohort A Participants 12Years to 18 Years	Cohort B Participants <12Years of Age	Cohort B Participants 12Years to 18 Years	Cohort C Participants <12Years of Age	Cohort C Participants 12Years to 18 Years
Arm/Group Description	Cohort A included pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT). Diagnostic imaging procedures included: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was allowed.	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Cohort B included pediatric participants (full-term newborns to <18 years) with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons. Diagnostic imaging procedures, US and MRI (with and without contrast enhancement) were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	A Sub-study with additional cohort C was initiated to collect diagnostic imaging procedures for the detection of CVC related DVT in a population < 18 years of age who had a CVC in place and who were scheduled to undergo a contrast enhanced MRI in any part of their body as part of their clinical care and who allowed the diagnostic imaging procedure to include the area around the CVC.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.
Measure Participants	32	45	7	7	32	11
Required Sedation for MRI	0 0%	0 NaN	1 NaN	0 NaN	17 NaN	0 NaN
Required Sedation for US	0 0%	0 NaN	0 NaN	0 NaN	3 NaN	0 NaN

6. Primary Outcome

Title	Number of Participants and Reasons for Non-Completion of Each of the Imaging Procedures, Ultrasound (US), MRI With Contrast and MRI Without Contrast
Description	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.
Time Frame	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).

Outcome Measure Data

Analysis Population Description

Participants had at least 1 radiographic procedure performed but were unable to complete a either an Ultrasound (neither bilateral or unilateral, or could complete only a unilateral US) and/or unable to complete an MRI with contrast and/or unable to complete an MRI without contrast.

Arm/Group Title	All Imaged Participants: No Ultrasound Performed	All Imaged Participants: Unilateral Ultrasound Performed	All Imaged Participants: No MRI Without Contrast Performed	All Imaged Participants: No MRI With Contrast Performed
Arm/Group Description	Participant had at least one radiographic imaging procedure performed but no study-related US (either bilateral or unilateral) was performed. Pediatric participants in which a CVC was to be placed or who had a CVC in place were included. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).	Participant had at least one radiographic imaging procedure performed but a study-related unilateral US instead of a bilateral US was completed. Bilateral US was the protocol-defined procedure but if the participant was not able to complete a bilateral US, then the unilateral US was accepted for evaluation. Pediatric participants in which a CVC was to be placed or who had a CVC in place were included. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).	Participant had at least one radiographic imaging procedure performed but no study-related MRI without contrast was performed. Pediatric participants in which a CVC was to be placed or who had a CVC in place were included. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).	Participant had at least one radiographic imaging procedure performed but no study-related MRI with contrast was performed. Pediatric participants in which a CVC was to be placed or who had a CVC in place were included. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).
Measure Participants	1	9	21	21
Investigator Decision	0 0%	4 NaN	2 NaN	1 NaN
Child Refused Procedure	0 0%	0 NaN	2 NaN	3 NaN
Parent Refused Procedure	0 0%	0 NaN	5 NaN	5 NaN
Difficulties with Anesthesia/Sedation	0 0%	0 NaN	3 NaN	3 NaN
Child Unable to Lie Still	0 0%	0 NaN	1 NaN	2 NaN
Problems with Contrast Administration	0 0%	0 NaN	0 NaN	1 NaN
Missed Appointment	1 0.7%	0 NaN	0 NaN	0 NaN
Parent or Child Refused to Continue US	0 0%	2 NaN	0 NaN	0 NaN
Other reasons	0 0%	3 NaN	8 NaN	6 NaN

7. Secondary Outcome

Title	Number of Deaths Which Occurred During the Study
Description	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.
Time Frame	Enrollment up to last US or MRI plus 30 days (up to approximately 90 days)

Outcome Measure Data

Analysis Population Description

The imaged population included all enrolled participants who had at least one study-related diagnostic imaging procedure.

Arm/Group Title	Cohort A	Cohort B	Cohort C
Arm/Group Description	Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia to be allowed. Participants enrolled in Cohort A and who developed symptoms of a venous thromboembolism (VTE), including a symptomatic DVT or a symptomatic pulmonary embolism (PE) prior to their MRI/US, should have been switched to Cohort B.	Pediatric Participants (full-term newborns to <18 years) with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	A Sub-study with additional cohort C was initiated to collect diagnostic imaging procedures for the detection of CVC-related DVT in a population < 18 years of age who had a CVC in place and who were scheduled to undergo a contrast enhanced MRI in any part of their body as part of their clinical care and who allowed the diagnostic imaging procedure to include the area around the CVC. Participants who developed symptoms of VTE prior to imaging should have been switched to Cohort B.
Measure Participants	77	14	43
Death due to any cause	0 0%	1 NaN	0 NaN
Death related to study procedures	0 0%	0 NaN	0 NaN

8. Primary Outcome

Title	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
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The imaged population included all enrolled participants who had at least one study-related diagnostic imaging procedure. n=number of adjudicated images

Arm/Group Title	Cohort A Newborn to <2Years	Cohort A 2Years to <12Years	Cohort A 12Years to <18Years	Cohort B Newborn to <2Years	Cohort B 2Years to <12Years	Cohort B 12Years to <18Years	Cohort C Newborn to <2Years	Cohort C 2Years to <12Years	Cohort C 12Years to <18Years
Arm/Group Description	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Pediatric participants in which a CVC was to be placed (intended stay for 40 ± 20 days) and who were asymptomatic for CVC-related deep vein thrombosis (DVT) were included in Cohort A. Diagnostic imaging procedures: ultrasound (US) and magnetic resonance imaging (MRI), with and without contrast enhancement. The MRI and US were to be done within 48 hours of each other. An approved gadolinium contrast agent at a dose which was considered 'state-of-the-art' or standard institutional practice at the specific site and in accordance with the country-specific regulatory guidance was to be used. No sedation or anesthesia was to be allowed.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC and who were either symptomatic for a CVC-related DVT or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons were enrolled into Cohort B. Diagnostic imaging procedures, US and MRI, were performed with and without contrast enhancement and were to be done within 48 hours of each other. Aesthesia/sedation allowed as routine standard of care for participants only if symptomatic for a CVC-related DVT. For those participants symptomatic for a CVC-related DVT, MRI and US were to be initiated within 7 days of symptoms. In those participants with an incidental diagnosis of a CVC-related DVT made by radiographic imaging performed for clinical reasons, MRI and US were to be done within 7 days of the diagnosis of the CVC-related DVT. If anticoagulation was started, ultrasound and MRI were to be done within 24 hours of each other.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.	Pediatric participants with a CVC in place and having an MRI for clinical reasons were enrolled in the substudy, Cohort C. An ultrasound was to be performed around the area of the CVC within 48 hours of the MRI. The MRI was performed both with and without contrast.
Measure Participants	2	30	45	1	6	7	4	28	11
DVTs (n=2,30,45,1,6,7,4,28,11)	1 0.7%	2 NaN	4 NaN	1 NaN	2 NaN	5 NaN	0 NaN	4 NaN	3 NaN
Diagnosis by US(n=2,30,45,1,6,7,4,28,11)	1 0.7%	2 NaN	4 NaN	1 NaN	2 NaN	4 NaN	0 NaN	3 NaN	2 NaN
Diagnosis by MRI w/o c (n=2,30,45,1,6,7,4,27,11)	0 0%	1 NaN	2 NaN	1 NaN	1 NaN	3 NaN	0 NaN	1 NaN	1 NaN
Diagnosis by MRI with c (n=2,30,45,1,6,6,4,28,11)	0 0%	1 NaN	2 NaN	1 NaN	1 NaN	2 NaN	0 NaN	0 NaN	2 NaN

9. Primary Outcome

Title	All Participants With an Adjudicated Deep Vein Thromboembolism (DVT) By Study-Related Radiographic Procedures That Diagnosed the DVT
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

n=participants with an adjudicated DVT identified by a study-related adjudicated radiographic procedure.

Arm/Group Title	All Imaged Participants
Arm/Group Description	All participants in Cohorts A, B, and C who had at least 1 radiographic procedure: Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed or who had a CVC in place. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related deep vein thrombosis (DVT) or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).
Measure Participants	22
Ultrasound (n=22)	19 14.2%
MRI with Contrast (n=20)	9 6.7%
MRI without Contrast (n=21)	10 7.5%

Adverse Events

Time Frame	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).
Adverse Event Reporting Description	Study initiated February 2011 and Last Patient, Last Visit was May 2013.
Arm/Group Title	All Imaged Participants
Arm/Group Description	All participants in Cohorts A, B, and C who had at least 1 radiographic procedure: Pediatric participants (full-term newborns to <18 years) in which a CVC was to be placed or who had a CVC in place. Participants were either asymptomatic (cohort A) or symptomatic for CVC-related deep vein thrombosis (DVT) or had an incidental diagnosis of CVC-related DVT by radiographic imaging performed for other clinical reasons (cohort B) or participants with a CVC in place and having an MRI with contrast for clinical reasons (Sub-study, cohort C).
All Cause Mortality
	All Imaged Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Imaged Participants
	Affected / at Risk (%)	# Events
Total	25/134 (18.7%)
Blood and lymphatic system disorders
Anaemia	1/134 (0.7%)
Febrile neutropenia	7/134 (5.2%)
Cardiac disorders
Ventricular tachycardia	1/134 (0.7%)
Gastrointestinal disorders
Pancreatitis acute	1/134 (0.7%)
Proctalgia	1/134 (0.7%)
General disorders
Device deployment issue	1/134 (0.7%)
Medical device complication	1/134 (0.7%)
Extravasation	1/134 (0.7%)
Asthenia	1/134 (0.7%)
General physical health deterioration	1/134 (0.7%)
Mucosal inflammation	1/134 (0.7%)
Thrombosis in device	3/134 (2.2%)
Pyrexia	3/134 (2.2%)
Infections and infestations
Skin infection	1/134 (0.7%)
Cellulitis	1/134 (0.7%)
Pneumonia	2/134 (1.5%)
Trichosporon infection	1/134 (0.7%)
Injury, poisoning and procedural complications
Subdural haematoma	1/134 (0.7%)
Investigations
Platelet count decreased	1/134 (0.7%)
Renal and urinary disorders
Renal impairment	1/134 (0.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/134 (0.7%)
Vascular disorders
Thrombosis	2/134 (1.5%)
Deep vein thrombosis	1/134 (0.7%)
Jugular vein thrombosis	3/134 (2.2%)
Embolism	1/134 (0.7%)
Venous occlusion	1/134 (0.7%)
Other (Not Including Serious) Adverse Events
	All Imaged Participants
	Affected / at Risk (%)	# Events
Total	15/134 (11.2%)
Gastrointestinal disorders
Nausea	7/134 (5.2%)
Vomiting	11/134 (8.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.