Optimal Duration of Anticoagulation in Deep Venous Thrombosis (MORGAGNI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Padova
Sponsor:
Information provided by (Responsible Party):
University of Padova
ClinicalTrials.gov Identifier:
NCT01285661
First received: April 30, 2010
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

Prospective cohort study aimed at optimizing the duration of anticoagulant treatment in patients at their first episode of proximal deep venous thrombosis (DVT) of the lower extremities, whose pathogenesis is either unknown (idiopathic DVT) or associated with minimal risk factors for thrombosis, with the help of an algorithm which incorporates both ultrasonography and D-dimer information. All patients will be followed-up for up to 4 years following recruitment. The purpose of this study is to demonstrate the safety of withholding anticoagulation from a subgroup of patients with proximal DVT whose veins have recanalized and present with a repeatedly negative D-dimer (at baseline, after 1 and 3 months). The approach will be deemed to be safe if the annual rate of recurrent VTE in patients who will have their anticoagulation discontinued is lower than 4%.


Condition Intervention Phase
Deep Venous Thrombosis of the Lower Extremities
Symptomatic Recurrent Venous Thromboembolism
Drug: Sodium warfarin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Padova:

Primary Outcome Measures:
  • Recurrent venous thromboembolism (VTE) [ Time Frame: Up to 4 years of follow-up ] [ Designated as safety issue: No ]
    To assess the rate of recurrent symptomatic VTE (expressed as rate/1000 patients-yeas) occurring after discontinuation of oral anticoagulant therapy up to the completion of 4 years of follow-up.


Secondary Outcome Measures:
  • Development of clinically relevant bleeding complications [ Time Frame: Up to 4 years of follow-up ] [ Designated as safety issue: Yes ]
    To assess the rate of major or clinically relevant bleeding complications (expressed as rate/1000 patients-years) occurring during the whole 4-year follow-up.

  • Development of clinically relevant bleeding complications occurring during the only period of anticoagulation [ Time Frame: Up to 4 years of follow-up ] [ Designated as safety issue: Yes ]
    Development of major or clinically relevant bleeding complications occurring during the only period of anticoagulation


Estimated Enrollment: 1250
Study Start Date: March 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 anticoagulation. 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 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 is positive or reverts to positive values in the following determinations will have their anticoagulation 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.
Other Names:
  • Vitamin K antagonists
  • Oral anticoagulants

Detailed Description:

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 4%. Assuming that on average anticoagulation can be withdrawn from 40% of patients 2 years after the qualifying thrombotic event, 1250 patients with proximal DVT satisfying the eligibility criteria are required to obtain 1000 years of observation without anticoagulation in 500 patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with proximal DVT that is idiopathic or secondary to minor factors for thrombosis, with or without contemporary manifestations of PE, who have completed an uneventful 3 to 12-month period of anticoagulation and are available for an overall 48-month follow-up at the study centre.

Exclusion Criteria:

  • previous thromboembolism
  • recent (less than 3 months) major trauma or surgery
  • active cancer
  • immobilization resulting from chronic irreversible medical diseases
  • need for indefinite anticoagulation for medical reasons other than VTE
  • impossibility to attend the follow-up visits or to have D-dimer determinations
  • already known major thrombophilia: carriage of deficiencies of natural anticoagulants, lupus-like anticoagulants, homozygosis for factor V Leiden or prothrombin mutation, heterozygosis for both abnormalities
  • short (less than 1 year) life expectancy
  • pregnancy
  • age younger than 18
  • refusal of informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285661

Contacts
Contact: Paolo Prandoni, MD, PhD +39 049 8212656 paoloprandoni@tin.it

Locations
Italy
Paolo Prandoni Recruiting
Padua, Italy, 35028
Contact: Paolo Prandoni, MD, PhD    +39 049 8212656    paoloprandoni@tin.it   
Principal Investigator: Paolo Prandoni, MD, PhD         
Sponsors and Collaborators
University of Padova
Investigators
Principal Investigator: Paolo Prandoni Department of Cardiothoracic and Vascular Sciences, University of Padua
  More Information

No publications provided

Responsible Party: University of Padova
ClinicalTrials.gov Identifier: NCT01285661     History of Changes
Other Study ID Numbers: 2001P
Study First Received: April 30, 2010
Last Updated: January 29, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by University of Padova:
Deep venous thrombosis
Pulmonary embolism
Ultrasonography
D-dimer
Venous thromboembolism
Bleeding

Additional relevant MeSH terms:
Thromboembolism
Thrombosis
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Vascular Diseases
Warfarin
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014