D-dimer to Predict Recurrence in Patients With Multiple Episodes of Venous Thromboembolism

The Negative Predictive Value of D-dimer on the Risk of Recurrent Venous Thromboembolism in Patients With Multiple Previous Events: a Prospective Cohort Study

Optimal duration of oral anticoagulant therapy in patients with recurrent episodes of venous thromboembolism (VTE) is a matter of debate and recommendations are based on inadequate evidence. More than 12 months of treatment are currently recommended, and the grade of recommendation is low.

The PROLONG study has recently evaluated the predictive role of D-dimer measurement after withholding oral anticoagulant treatment in patients with a first episode of VTE. Patients with a positive D-dimer had a significantly higher incidence of VTE recurrences than patients with a negative D-dimer and required resumption of the antithrombotic treatment. Based on the results of this and of previous cohort studies, it appears safe to withhold treatment in patients with negative D-dimer values and to continue treatment in patients with altered D-dimer levels.

Aim of this study is therefore to assess the negative predictive value of D-dimer also in patients with recurrent VTE and to evaluate the clinical utility of this approach in this patient setting.

Study Overview

• Status: Terminated
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Warfarin

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Varese, Italy, 21100
    • University of Insubria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism)
• Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases
• Age > 18 years
• Informed consent provided

Exclusion Criteria:

• Pregnancy/puerperium
• One or more episodes of massive pulmonary embolism
• Last event isolated idiopathic pulmonary embolism
• Two or more idiopathic VTE events
• First degree relatives with recurrent VTE
• Right ventricular disfunction or pulmonary hypertension
• Active cancer
• Antiphospholipid antibodies syndrome
• Antithrombin deficiency
• Homozygous Factor V Leiden or G20210A prothrombin mutation
• Heterozygous Factor V Leiden and G20210A prothrombin mutation
• Concomitant congenital thrombophilic mutations
• Concomitant indications to long term oral anticoagulant treatment
• Severe cardiorespiratory insufficiency
• Severe liver or renal disease (creatinine clearance > 2 mg/dL)
• Limited life expectancy
• Geographic inaccessibility

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent Deep Vein Thrombosis or Pulmonary Embolism in Patients With Persistently Negative D-dimer Levels	Objectively documented deep vein thrombosis, pulmonary embolism, superficial vein thrombosis	1 year
Rate of Patients With Altered D-dimer Levels and Temporal Distribution of Alterations		3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	3 months
Recurrent Deep Vein Thrombosis or Pulmonary Embolism in Patients Who Resumed Oral Anticoagulant Therapy	3 months
Incidence of Major Bleeding in Patients Who Resumed Oral Anticoagulant Therapy	3 months

Collaborators and Investigators

• Sponsor: Università degli Studi dell'Insubria
• Investigators: Study Chair: Gualtiero Palareti, University of Bologna; Study Director: Walter Ageno, Università degli Studi dell'Insubria; Study Director: Vittorio Pengo, University of Padova

Publications and helpful links

General Publications

• Palareti G, Legnani C, Cosmi B, Guazzaloca G, Pancani C, Coccheri S. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost. 2002 Jan;87(1):7-12.
• Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A, Pengo V, Ghirarduzzi A, Pattacini C, Testa S, Lensing AW, Tripodi A; PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med. 2006 Oct 26;355(17):1780-9. doi: 10.1056/NEJMoa054444. Erratum In: N Engl J Med. 2006 Dec 28;355(26):2797.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: January 26, 2007
• First Submitted That Met QC Criteria: January 29, 2007
• First Posted (Estimate): January 30, 2007

Study Record Updates

• Last Update Posted (Estimate): September 26, 2011
• Last Update Submitted That Met QC Criteria: August 18, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Recurrence; D-dimer; Venous thromboembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Anticoagulants; Warfarin
• Other Study ID Numbers: 2175