Optimal Duration of Anticoagulation in Deep Venous Thrombosis (MORGAGNI)
|Deep Vein Thrombosis of Lower Limb Lower Extremity Deep Venous Thrombosis Recurrent||Drug: Sodium warfarin||Phase 3|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Identification of the Optimal Duration of Anticoagulation in Patients With Deep Venous Thrombosis of the Lower Extremities With the Use of Residual Vein Thrombosis in Combination With D-Dimer|
- Recurrent venous thromboembolism (VTE) [ Time Frame: Up to the study conclusion (see the study protocol) ]To assess the rate of recurrent symptomatic VTE (expressed as rate/1000 patients-yeas) occurring after discontinuation of oral anticoagulant therapy up to the study conclusion.
- Development of major bleeding complications [ Time Frame: Up to the study conclusion (see the study protocol) ]To assess the rate of major or clinically relevant bleeding complications (expressed as rate/1000 patients-years) occurring during oral anticoagilant therapy up to the study conclusion
|Study Start Date:||March 2010|
|Study Completion Date:||October 2015|
|Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Proximal DVT
Patients whose veins have recanalized (either at the recruitment or later on during the follow-up) will receive the D-dimer determination before discontinuing sodium warfarin. Veins are defined as recanalized when the vein diameter under maximum compressibility is lower than 4 mm both at the common femoral and at the popliteal vein. In those with negative D-dimer sodium warfarin will be discontinued. These patients will have two further determinations of D-dimer (after 1 and 3 months, respectively). While patients with persistently negative D-dimer will no longer receive sodium warfarin, those in whom D-dimer is positive or reverts to positive values in the following determinations will have their sodium warfarin resumed and no longer discontinued.
Drug: Sodium warfarin
Patients with early vein recanalization, as shown by ultrasonography, and repeatedly negative D-dimer will have anticoagulation discontinued. They will be followed-up for up to 4 years after recruitment in order to assess the rate of recurrent symptomatic VTE. In all other patients anticoagulation will not be discontinued.
After giving informed consent, patients will receive an ultrasound investigation of the proximal-vein system (common femoral vein at groin, popliteal vein up to its trifurcation):
- Patients with residual thrombosis (defined as a diameter of at least 4 mm in at least one spot) will have their anticoagulation continued. A repeat ultrasound is scheduled after 6, 12, 18, 24 and 36 months. In patients with persistently residual thrombosis anticoagulation will not be discontinued, while those whose veins have recanalized will have a decision making process based on the behaviour of D-dimer (see below).
- Patients whose veins have recanalized (either at the recruitment or later on) will receive the D-dimer determination before discontinuing anticoagulation. In those with negative D-dimer anticoagulation will be discontinued. These patients will have two further determinations of D-dimer (after 1 and 3 months, respectively). While patients with persistently negative D-dimer will no longer receive anticoagulation, those in whom D-dimer becomes positive will have their anticoagulation resumed and no longer discontinued.
- All patients will be followed up to completion of 4 years since recruitment. For the purpose of this study each quantitative D-dimer is allowed. The criterion for D-dimer interpretation will rely on the cut-off that is recommended by manufacturers for diagnostic purposes.
D-dimer.For the purpose of this study each quantitative D-dimer is allowed. The criterion for D-dimer interpretation will rely on the cut-off that is recommended by manufacturers for diagnostic purposes.
Sample size 1000 years of observation without anticoagulation are required to demonstrate (power 90%, type I error 0.05, two sided) that with this approach the annual rate of recurrent VTE is lower than 5%. Approximately 600 patients with proximal DVT satisfying the eligibility criteria are required to obtain 1000 years of observation without anticoagulation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285661
|Padua, Italy, 35028|
|Principal Investigator:||Paolo Prandoni||Department of Cardiothoracic and Vascular Sciences, University of Padua|