The primary objective of the study is to assess the safety of a normal MRDTI to rule out acute, recurrent ipsilateral proximal DVT in a prospective, multicenter, single-arm management (cohort) study.Secondary objectives are:1.To evaluate the safety…
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Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the 3-month incidence of recurrent VTE in patients with
MRDTI that is negative for the presence of DVT. The primary sensitivity
analysis is restricted to patients who did not receive anticoagulants in the
follow-up period. Symptomatic DVT of both the ipsilateral as contralateral leg
is defined as symptoms suggestive of acute DVT, i.e. ongoing pain, swelling,
tenderness, warmth and/or erythema of the leg of recent onset, and
non-compressibility of the common femoral and/or popliteal vein in a new venous
segment, or a pronounced increase in vein diameter (>= 4 mm) of a previously
uncompressible vein as compared to the reference CUS performed at baseline.
Acute PE is defined as at least one filling defect in the pulmonary artery tree
on CTPA. In addition, PE is considered as the cause of any unexplained death
unless autopsy will prove otherwise. All primary endpoints will be adjudicated
by an independent Clinical Events Committee (see section on Monitoring).
Secondary outcome
The secondary endpoints include:
1 Post-hoc assessment of the 3-month incidence of recurrent VTE after the
baseline combination of a normal D-dimer test (for patients aged over 50 years
age x 10 µg/l, for patients aged 50 years or younger 500 µg/l), and an unlikely
ruling by the Wells score for DVT (Appendix B). The golden standard for a
correct negative ruling by the D-dimer test and the clinical decision rule is a
normal MRDTI at baseline and an uneventful 3-month follow-up period;
2 Feasibility of MRDTI as diagnostic test in daily clinical practice, i.e. the
number of patients that could not be managed according to the study protocol
due to logistical or technical issues and the mean time from presentation to
MRDTI ruling;
3 Post-hoc assessment of the inter-observer variability of MRDTI in clinical
practice: 100 MRDTI scans (first 10 scans of each study site) will be
re-assessed after the study by 2 independent radiologists, who are blinded tot
the clinical presentation and follow-up of the study patients. Their ruling
will be compared to the ruling of the attending radiologist at the moment of
clinical presentation;
4 A cost-effectiveness (KEA) and cost-utility analysis (KUA). Both will be
dependent on data derived from this study as well as data from the literature.
The KEA will provide en estimation of the total costs associated with
diagnostic tests for one prevented false-positive diagnosis. The KUA will be
additionally be based on estimated costs for patient monitoring, bleeding
complications and productivity costs. Assessment of quality-adjusted life-years
(QALY) after a MRDTI based diagnostic strategy will be compared to a CUS-bases
strategy, using cost-utility models as proposed by the British National
Institute for Health and Clinical Excellence (NICE), specified for Dutch norms
Background summary
The diagnostic management of suspected ipsilateral recurrent proximal deep vein
thrombosis (DVT) is complicated by critical limitations to current available
diagnostic techniques, mainly caused by persistent intravascular abnormalities
after a first DVT. Compression ultrasonography (CUS) is the imaging method of
choice, although CUS can only diagnose ipsilateral recurrent DVT with some
certainty in case of a new uncompressible venous segment, or a pronounced
increase in vein diameter of a previously uncompressible vein as compared to a
reference CUS, assessed after successful treatment of the first DVT. In
clinical practice however, this reference CUS is seldomly available and
comparisons with previous CUS examinations are subject to major inter-observer
variability. Consequently, recurrent ipsilateral DVT cannot be ruled out in
20-30% of patients, who are therefore all subjected to lifelong anticoagulant
therapy with associated high bleeding risk.
Magnetic resonance direct thrombus imaging (MRDTI) has been shown to accurately
diagnose a first DVT episode and to reliably distinguish chronic residual
thrombotic scars from acute recurrent DVT. MRDTI could therefore potentially be
used as a single test in the diagnostic management of clinically suspected
recurrent ipsilateral DVT. We hypothesize that MRDTI has equally high safety
(sensitivity) but superior efficacy (specificity) compared to CUS in this
setting.
Study objective
The primary objective of the study is to assess the safety of a normal MRDTI to
rule out acute, recurrent ipsilateral proximal DVT in a prospective,
multicenter, single-arm management (cohort) study.
Secondary objectives are:
1.To evaluate the safety of ruling out acute recurrent ipsilateral DVT based on
a normal D-dimer test result in combination with an unlikely ruling by the
Wells rule for DVT
2.To assess the health economics of a MRDTI-based diagnostic algorithm for
suspected recurrent ipsilateral DVT compared to a CUS-based algorithm.
Study design
The Theia-study is a prospective, multicenter, single-arm management (cohort)
study.
Consecutive patients with clinically suspected acute, recurrent, ipsilateral,
proximal DVT, who fulfil all the inclusion criteria and meet none of the
exclusion criteria, are eligible for inclusion and will be managed according to
the result of a MRDTI of the affected leg. The MRDTI is to be performed and
adjudicated within 24 hours of study inclusion. The final treatment decision
will be made based on this ruling of the MRDTI. In case of a positive MRDTI
signal, patients will be treated with therapeutically dosed anticoagulants.
Patients with a negative MRDTI ruling will be subjected to a standardized CUS
within 48 hours after initial presentation. The latter CUS serves as a
reference test in case the patient returns with symptoms of ipsilateral
recurrence in the future, and will not be used for management decisions at
baseline. The study flowchart can be found in Appendix A.
All patients will be followed for three months for the occurrence of acute
recurrent venous thrombo-embolism (VTE). In case of suspected recurrent VTE,
objective testing including either computed tomography pulmonary angiography
(CTPA) for PE or CUS for DVT will be performed. Additionally, in case of a
proven ipsilateral recurrent DVT during follow-up, MRDTI will be repeated.
Study burden and risks
Currently, the diagnostic management of patients with suspected acute,
recurrent, ipsilateral, proximal DVT is far from accurate. Hence, relevant
patients may receive a false positive CUS finding and by that, may be subjected
wrongfully to indefinite therapeutic anticoagulation with its associated
bleeding complications.
The very sensitive and specific MRDTI technique has been shown to be a reliable
imaging modality to distinguish acute from chronic thrombi in the leg veins.
This technique does not require administration of potential toxic contrast dye,
or ionizing radiation, and takes only 15 minute of time. Hence, no harmful
effect s of the MRDTI can be expected and on the other hand, some patients may
directly benefit from this study.
The potential therapeutic advantage for the study patients comes at cost of a
potential longer waiting time from moment of presentation at the outpatient
clinic or emergency ward, to the definite diagnostic decision. In addition,
after a negative MRDTI, an additional CUS is required for the study, which will
also take some time. Even so, patients will be well informed of this before
study inclusion.
Albinusdreef 2
Leiden 2300RC
NL
Albinusdreef 2
Leiden 2300RC
NL
Listed location countries
Age
Inclusion criteria
1 Ability of subject to understand the character and individual consequences of this study;
2 Signed and dated informed consent of the subject available before the start of any specific study procedures;
3 Age >=18 years;
4 Suspected acute recurrent ipsilateral DVT, as defined by a documented prior objectivated episode of DVT in the same leg as current symptoms originate from
Exclusion criteria
1 General contraindications for MRI: claustrophobia, first trimester of pregnancy, intracranial vascular clips, any ferromagnetic implants, presence of a cardiac pacemaker or defibrillator, metallic splinters in the eye, any trauma or surgery which may have left ferromagnetic material in the body;
2 CUS-proven acute symptomatic DVT within 6 months before current presentation;
3 Onset of symptoms suggestive of acute recurrent DVT more than 10 days prior to presentation;
4 Suspected acute PE;
5 Hemodynamic instability at presentation (as a consequence of concurrent acute PE or otherwise);
6 Medical or psychological condition that would not permit completion of the study or signing of informed consent, including life expectancy less than 3 months
8 Non-compliance or inability to adhere to treatment or follow-up visits.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 |
|---|---|
| CCMO | NL50663.058.14 |