Primary Objectives:To (1) Assess the feasibility and tolerability of performing US and/or contrast-enhanced MRI in children with central venous catheters (CVCs) or peripherally inserted central catheters (PICC lines); (2) assess the accuracy of US…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measures will include:
* The number of subjects recruited into the study that are able to undergo each
one of the imaging procedures (ultrasound and MRI) that are performed at Visit
1. Visit 1, is defined for Cohort A subjects as day 40 ± 20 days from the
placement of the CVC, or if possible within 72 hours after a CVC is removed or
lost. For Cohort B subjects Visit 1 is defined as within 7 days of initiation
of symptoms of a CVC-related DVT or within 7 days of an incidental diagnosis of
CVC-related DVT by radiographic imaging.
* The frequency and nature of difficulties encountered during each one of the
imaging procedures that are performed at Visit 1. Visit 1, is defined for
Cohort A subjects as day 40 ± 20 days from the placement of the CVC, or if
possible within 72 hours after a CVC is removed or lost. For Cohort B subjects
Visit 1 is defined as within 7 days of initiation of symptoms of a CVC-related
DVT or within 7 days of an incidental diagnosis of CVC-related DVT by
radiographic imaging.
* Frequency of subjects with a DVT detected by the ultrasound and/or MRI at
Visit 1 and confirmed by adjudication. Visit 1, is defined for Cohort A
subjects as day 40 ± 20 days from the placement of the CVC, or if possible
within 72 hours after a CVC is removed or lost. For Cohort B subjects Visit 1
is defined as within 7 days of initiation of symptoms of a CVC-related DVT or
within 7 days of an incidental diagnosis of CVC-related DVT by radiographic
imaging.
Secondary outcome
The secondary outcomes measures will include:
* Frequency of subjects in Cohort A with asymptomatic for CVC-related DVT
identified by the investigator at enrollment and confirmed by at least one
adjudicated diagnostic imaging procedure performed at Visit 1. Visit 1, is
defined for Cohort A subjects as day 40 ± 20 days from the placement of the
CVC, or if possible within 72 hours after a CVC is removed or lost.
* Frequency of symptomatic subjects in Cohort B with CVC-related DVT
identified by the investigator at enrollment and confirmed by at least one
adjudicated diagnostic imaging procedure performed at Visit 1. Visit 1, is
defined for defined for Cohort B subjects as within 7 days of initiation of
symptoms of a CVC-related DVT or within 7 days of an incidental diagnosis of
CVC-related DVT by radiographic imaging.
* Frequency of subjects in Cohort B with or without symptoms for CVC-related
DVT, who have been incidentally identified by radiographic imaging performed
for other clinical reasons as having a CVC-related DVT in the veins where the
current catheter is placed, identified by the investigator at enrollment and
confirmed by at least one adjudicated diagnostic imaging procedure performed at
Visit 1. Visit 1 is defined for Cohort B subjects as within 7 days of
initiation of symptoms of a CVC-related DVT or within 7 days of an incidental
diagnosis of CVC-related DVT by radiographic imaging.
* Frequency of asymptomatic subjects enrolled in Cohort A developing symptoms
of a VTE, including DVT or PE, identified by the investigator between
enrollment and Visit 1 and confirmed by at least one adjudicated diagnostic
imaging procedure performed within 7 days of the initiation of symptoms. The
period between enrollment and Visit 1 is defined for Cohort A subjects as from
the time of enrollment up to 60 days after the CVC has been placed, or from the
time of enrollment up to 72 hours after the CVC is removed or lost
*Frequency of adjudicated PE events (symptomatic or asymptomatic) identified
during the course of the study as defined from enrollment up to 30 days
following the study radiographic procedures (MRI and/or Ultrasound).
* Frequency of adjudicated death events occurred during the course of the study
as defined from enrollment up to 30 days following the study radiographic
procedures (MRI and/or Ultrasound).
Background summary
Deep Vein thrombosis (DVT) occurs in children as a secondary complication of
multiple risk factors related to underlying disease and its treatment. DVT is
most commonly related to the presence of central venous catheters (CVC),
particularly in patients with cancer.
Children with a CVC develop DVT in 25 - 70% of cases depending on age and the
underlying disease. Reported incidence rates also depend on the imaging
procedure used for diagnosis and trial design. About two thirds of DVT in
children occur in the upper body central venous system, reflecting the most
common location of the CVC placement. Most CVC-related DVT are asymptomatic,
however, there is a growing body of information that asymptomatic DVTs are of
clinical significance.
Ultrasound (US) is the most frequently used test for diagnosis of DVT because
of its ease of use, non-invasiveness, and its excellent accuracy for diagnosis
of DVT in the lower extremities. For diagnosis of CVC-related DVT in the upper
venous system, a combination of venography and ultrasound is currently
considered the reference standard. However, conventional venography has
limitations, particularly in children, because of its invasive nature,
technical demands, costs, adverse effects associated with nephrotoxic contrast
media, and radiation exposure.
Contrast-enhanced magnetic resonance imaging (MRI) is an attractive alternative
allowing comprehensive imaging of the central venous system. Advantages of
contrast-enhanced MRI are that it is minimally invasive, does not involve
radiation, and magnetic resonance contrast media are well tolerated. An added
value of contrast-enhanced magnetic resonance is that it allows simultaneous
evaluation of the pulmonary vasculature for presence of Pulmonary Embolism
(PE).
To date, only two pediatric studies have reported on the use of
contrast-enhanced MRI in children in the lower and upper venous system, but
there was no systematic comparison to other diagnostic imaging procedures. The
feasibility and diagnostic accuracy of contrast enhanced MRI for CVC-related
DVT in children remains to be established.
Study objective
Primary Objectives:
To (1) Assess the feasibility and tolerability of performing US and/or
contrast-enhanced MRI in children with central venous catheters (CVCs) or
peripherally inserted central catheters (PICC lines); (2) assess the accuracy
of US and/or MRI for detection of CVC-related DVT in the venous region of CVC
placement (jugular, subclavian, and femoral CVC) and identify the best
combination of tests for reliable assessment of CVC-related DVT.
Secondary Objectives:
To (1) assess the accuracy of clinical diagnosis of DVT versus US, MRI, or
both; (2) Assess the event rate of adjudicated PE; (3) Assess the event rate of
adjuducated death.
Study design
CV185077 is an interventional non-therapeutic study to select the diagnostic
techniques to detect DVT in children (full-term newborn to < 18 years old) with
an indwelling CVC. The children will be subdivided into three cohorts.
Cohort A (asymptomatic subjects) will have a CVC placed for at least 40 ± 20
for which Day 0 is the day of catheter placement and Day 40 ± 20 is the day of
the diagnostic imaging procedure. Asymptomatic subjects will have their
diagnostic imaging procedures done without sedation or anesthesia. Subjects
enrolled in Cohort A who develop symptoms of a DVT prior to their diagnostic
imaging procedures will be switched into Cohort B.
Cohort B (symptomatic subjects) will consist of those subjects who have an
indwelling CVC and have symptoms of a suspected DVT 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 and may not have symptoms of a DVT. Diagnostic imaging procedures should
be initiated within 7 days of symptoms of a CVC-related DVT or within 7 days of
the incidental diagnosis of a CVC-related DVT by radiographic imaging.
Symptomatic subjects may undergo sedation/anesthesia for the diagnostic imaging
procedures if approved by the subject care team, parents, and subject (when
older than 12 years). All Cohort B subjects are allowed to be started on
therapeutic anti-coagulation for the treatment of their thrombosis, if the
investigator considers appropriate. If anticoagulation is started, the second
radiographic procedure should be performed within 24-hours of the first
radiographic procedure.
Cohort C (asymptomatic subjects) will collect diagnostic imaging procedures for
subjects up to 18 years of age who have a CVC in place and who are scheduled to
undergo a contrast enhanced MRI in any part of their body as part of their
clinical care and will allow the diagnostic imaging procedure to include the
area around the CVC.
The final visit will occur within 30 days after the US/contrast-enhanced MRI to
assess for any non-serious and serious adverse events.
An independent Central Adjudication Committee (ICAC) will adjudicate all
ultrasounds and contrast-enhanced MRIs for suspected symptomatic and
asymptomatic VTEs.
Intervention
Performance of contrast-enhanced MR Imaging with Gadolinium contrast injection.
Administration of the anesthesia or sedation as per standard of care for
symptomatic patients.
Study burden and risks
This study is evaluating sophisticated diagnostic imaging procedures for
CVC-DVT detection that will allow for proper diagnostic techniques to be used
in safety and efficacy studies for a new anti-coagulant, apixaban, for
prevention of catheter related thrombosis in children.
Asymptomatic children in cohort A will undergo ultrasonography and MRI after
20-60 days with a catheter. Ultrasonography is an easy to perform, painless,
non-invasive method without radiation. For MRI the children need to receive
contrast. Problems with contrast are very rare and occur mainly in patients
with moderate-severe kidney failure. These patients are not eligible for this
study. The contrast will be given using the CVC, so without venapuncture. Only
gadolinium products approved by the regulatory authorities and ethics
committees for children in each age category will be used.
Patients in cohort C will get MRI for other reasons and according to this study
an additional ultrasonography. Ultrasonography is a non-invasive method without
radiation, as described above.
For children in cohort A and C asymptomatic DVT might be diagnosed. The
physician could decide to treat these patients with anticoagulation in case of
severe thrombosis and pulmonary embolism to prevent enlargement of thrombi or
to do a follow-up diagnostic test to follow the thrombus.
In symptomatic children (cohort B) ultrasonography is used to detect DVT,
usually in combination with venography. In this study a MRI will be used
instead of venography. In contrast to venography, MRI is not invasive (contrast
can be injected in the central venous catheter instead of the veins of the
hand), and does not involve radiation. Furthermore, it allows simultaneous
evaluation of the pulmonary vasculature for presence of pulmonary embolism
which is not possible with venography.
Vijzelmolenlaan 9
3440 AM Woerden
NL
Vijzelmolenlaan 9
3440 AM Woerden
NL
Listed location countries
Age
Inclusion criteria
Signed Written Informed Consent
Target Population
2) Functioning CVC in the upper or lower venous system (eg, jugular, subclavian; femoral vein)
3) Cohort A: Asymptomatic subjects having placement of a new, indwelling CVC in the last 40±20 days
4) 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.;Age and Reproductive Status
5) Males and females from full-term newborns to < 18 years
6) Women must have a negative serum or urine pregnancy test
Exclusion criteria
1) Failure to provide written consent from parents or guardians
Target Disease Exceptions
2) For cohort A subjects only, present therapeutic dosing of systemic 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.;Medical History and Concurrent Diseases
3) Children unable to undergo contrast-enhanced MRI
4) Pacemaker, osteosynthesis material implanted within the last month;Physical and Laboratory Test Findings
5) Abnormal baseline laboratory test results:
* Renal function < 50% of normal for age and size
6) Positive pregnancy test;Allergies and Adverse Drug Reaction
7) Allergy to gadolinium;Other Exclusion Criteria
8) Prisoners or subjects who are involuntarily incarcerated
9) Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01137578 |
| CCMO | NL32819.018.10 |