Clinical trial NCT02262052: Advanced Diagnostic Management of Suspected Recurrent Ipsilateral DVT With MRDTI
Official title: Advanced Diagnostic Management of Suspected Recurrent Ipsilateral Deep Vein Thrombosis of the Leg With Magnetic Resonance Direct Thrombus Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Deep Vein Thrombosis
Keywords: Deep vein thrombosis
Diagnostic management
Recurrent
MRI
Ipsilateral
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Trombosestichting Nederland
First posted: 2014-10-10
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The Theia-study is a prospective, multicenter, single-arm management (cohort) study.

Consecutive patients with clinically suspected acute, recurrent, ipsilateral, proximal deep vein thrombosis (DVT) of the leg, 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 magnetic resonance direct thrombus imaging (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 or modified in patients with a recurrent DVT on anticoagulant therapy. Patients with a negative MRDTI ruling will be left untreated, or treatment will be remained unadjusted if they are on anticoagulant treatment at inclusion. All patients with negative MRDTI will be subjected to a standardized compression ultrasonography (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.

Detailed description: See below.

Eligibility criteria: 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, 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, or unwillingness to sign informed consent;
7. Non-compliance or inability to adhere to treatment or follow-up visits.
8. Patients with suspected acute, recurrent, ipsilateral DVT on therapeutic anticoagulant treatment \> 48 hours at inclusion\*

Note: \*From August 2015 onward, patients with suspected acute, recurrent, ipsilateral DVT on anticoagulant treatment were allowed in the study as they were found to represent a high proportion (30%) of the screened study population.

Primary outcomes:
measure: 3-month incidence of recurrent VTE in patients with negative MRDTI
timeFrame: 3-month follow-up
Secondary outcomes:
measure: 3-month incidence of recurrent VTE in patients with normal D-dimer test and unlikely clinical probability according to the Wells clinical decision rule for DVT
timeFrame: 3-month follow-up
Other outcomes:
measure: The feasibility of MRDTI in day to day clinical practice
timeFrame: First 24 hours after presentation to the emergency ward (post-hoc analysis)
measure: Inter-observer variability of MRDTI
timeFrame: After the study has been completed, all MRDTI studies will be re-evaluated (post-hoc analysis)
measure: a formal cost-effectiveness and cost-utility analysis
timeFrame: This model will be based on the primary and secondary endpoints, scored after a follow-up period of 3 months (post-hoc analysis)
Locations:
city: Ottawa
country: Canada
facility: Ottawa Hospital
city: Haifa
country: Israel
facility: RAMBAM Healthcare center
city: Amsterdam
country: Netherlands
facility: AMC
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Leiden
country: Netherlands
facility: LUMC
city: The Hague
country: Netherlands
facility: HAGA
city: The Hague
country: Netherlands
facility: MCH Westeinde
city: Utrecht
country: Netherlands
facility: Diakonessenhuis Utrecht
city: Utrecht
country: Netherlands
facility: UMCU
city: Grålum
country: Norway
facility: Ostfold Hospital Trust
city: Stockholm
country: Sweden
facility: Danderyds sjukhus
Study officials:
affiliation: Department of Thrombosis and Hemostasis, LUMC, Leiden
name: F.A. Klok Klok, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Thrombosis and Hemostasis, LUMC, Leiden
name: M.V. Huisman, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Radiology, LUMC, Leiden
name: L.J.M. Kroft, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tan M, Mol GC, van Rooden CJ, Klok FA, Westerbeek RE, Iglesias Del Sol A, van de Ree MA, de Roos A, Huisman MV. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis. Blood. 2014 Jul 24;124(4):623-7. doi: 10.1182/blood-2014-04-566380. Epub 2014 Jun 13.
citation: Westerbeek RE, Van Rooden CJ, Tan M, Van Gils AP, Kok S, De Bats MJ, De Roos A, Huisman MV. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg. J Thromb Haemost. 2008 Jul;6(7):1087-92. doi: 10.1111/j.1538-7836.2008.02986.x. Epub 2008 Jul 1.
citation: van Dam LF, Dronkers CEA, Gautam G, Eckerbom A, Ghanima W, Gleditsch J, von Heijne A, Hofstee HMA, Hovens MMC, Huisman MV, Kolman S, Mairuhu ATA, Nijkeuter M, van de Ree MA, van Rooden CJ, Westerbeek RE, Westerink J, Westerlund E, Kroft LJM, Klok FA; Theia Study Group. Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis. Blood. 2020 Apr 16;135(16):1377-1385. doi: 10.1182/blood.2019004114.