DULCIS (D-dimer and ULtrasonography in Combination Italian Study)

NCT00954395 | Completed DMC

• 1 other identifier: DULCIS
• Study Type: observational
• Target: 1,100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of a standardized procedure to establish the optimal duration of anticoagulation in patients with venous thromboembolism.

Conditions

Venous Thromboembolism

Keywords

vitamin K antagonists, D-dimer,; deep vein thrombosis, pulmonary embolism,

Outcome Measures

Primary Outcomes (1)

• Recurrent venous thromboembolism (VTE) and major and minor but clinically relevant bleeding

  two years after enrollment

Study Arms (2)

1. anticoagulation suspension

eligible patients undergo measurement of residual venous obstruction (RVO) with compression ultrasound (CUS) in case of a previous deep vein thrombosis (DVT) and/or of pulmonary artery pressure (PAP) with echocardiography in case of previous pulmonary embolism (PE). In patients with RVO is less \< 4 mm in case of a previous DVT and/or PAP is normal with echocardiography in case of previous PE and in those who have undergone additional 6 months of therapy for previously altered RVO, D-dimer is measured during anticoagulation. If D-dimer is below age and gender cut-offs , anticoagulation is interrupted and D-dimer is then re-assessed after 15, 30, 60 and 90 days. If all the D-dimer measurements are below the cut-offs, anticoagulation is definitely interrupted and patients are followed-up for two years.

Other: D-dimer

2. anticoagulation prolongation

If RVO is greater than 4 mm at CUS of the lower limbs and/or PAP is increased (\> 35 mmHg, \> 40 mmHg in the elderly or obese), anticoagulation is prolonged for additional 6 months and the measures of RVO and/oR PAP are repeated. In those in whom PAP is altered also after 6 months of additional therapy, anticoagulation is prolonged. In patients with RVO is less \< 4 mm in case of a previous DVT and/or PAP is normal with echocardiography in case of previous PE and in those who have undergone additional 6 months of therapy for previously altered RVO, D-dimer is measured during anticoagulation. If D-dimer is above age and gender cut-offs , anticoagulation is prolonged. If D-dimer is below the cut-offs , anticoagulation is interrupted and D-dimer is then re-assessed after 15, 30, 60 and 90 days. If one of these D-dimer measurement is above the cut-off , anticoagulation is resumed for at least 6 months and patients are re-evaluated.

Other: D-dimer

Interventions

D-dimer OTHER

D-dimer is performed at the time of anticoagulation suspension. If above or below age and gender specific cut-offs, anticoagulation is stopped and D- dimer repeated after 15, 30, 60 and 90 days.

Also known as: D-dimer, fibrin fibrinogen degradation products

1. anticoagulation suspension; 2. anticoagulation prolongation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a first episode of venous thromboembolism attending anticoagulation clinics or general practitioners

You may qualify if:

• Age \> 18 years first episode of objectively documented symptomatic idiopathic VTE, either proximal lower extremity deep vein thrombosis (DVT) and/or pulmonary embolism (PE).
• Unprovoked or idiopathic , or associated with one or more of the following favouring factors
• · - minor general surgery, arthroscopy or laparoscopy
• pregnancy or puerperium
• hormonal treatment (contraceptive or replacement therapy)
• travel
• minor traumas
• hospitalization in a medical ward
• reduced mobility (non complete immobilization) at least six months of VKA therapy ( or other type) for at least 3 months and not longer than 12 months ability to provide informed consent

You may not qualify if:

• Index event was isolate distal ( calf) vein thrombosis
• Index event was PE associated with shock or prolonged hypotension at high risk
• Index event was DVT in sites different from the lower limbs
• Pregnancy or puerperium ( first 6 weeks after delivery) at the time of the visit
• Solid or haematological malignancy in the active phase or undergoing chemotherapy or radiotherapy
• Antiphospholipid antibody syndrome, diagnosed according to the Sydney criteria
• Hereditary antithrombin deficiency
• Necessity to prolong anticoagulation for any reason (due to the thrombotic event or other clinical indications
• Severe respiratory or heart failure (NYHA classes: III or IV)
• Presence of criteria indicating a short anticoagulant treatment:
• Venous thromboembolism secondary to one of the following triggering factors:
• Major surgery \[orthopedic, general, oncological (only if radical)\]
• Bed rest (\>4 dd)
• Severe trauma
• Plaster cast of the lower limbs

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead
• University of Bologna: collaborator

Study Sites (1)

U.O. Angiologia e Malattie della Coagulazione "Marino Golinelli"; Dipartimento Cardio-Toraco-Vascolare Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

Related Publications (7)

• 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.

  PMID: 17065639 BACKGROUND

• Legnani C, Palareti G, Cosmi B, Cini M, Tosetto A, Tripodi A; PROLONG Investigators (FCSA and Italian Federation of Thrombosis Centers). Different cut-off values of quantitative D-dimer methods to predict the risk of venous thromboembolism recurrence: a post-hoc analysis of the PROLONG study. Haematologica. 2008 Jun;93(6):900-7. doi: 10.3324/haematol.12320. Epub 2008 Apr 28.

  PMID: 18443269 BACKGROUND

• Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):454S-545S. doi: 10.1378/chest.08-0658.

  PMID: 18574272 BACKGROUND

• Prandoni P, Lensing AW, Prins MH, Bernardi E, Marchiori A, Bagatella P, Frulla M, Mosena L, Tormene D, Piccioli A, Simioni P, Girolami A. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med. 2002 Dec 17;137(12):955-60. doi: 10.7326/0003-4819-137-12-200212170-00008.

  PMID: 12484710 BACKGROUND

• Pengo V, Prandoni P. From acute pulmonary embolism to chronic thromboembolic pulmonary hypertension. Ital Heart J. 2005 Oct;6(10):830-3.

  PMID: 16270475 BACKGROUND

• Palareti G, Cosmi B, Antonucci E, Legnani C, Erba N, Ghirarduzzi A, Poli D, Testa S, Tosetto A, Pengo V, Prandoni P; DULCIS investigators. Duration of anticoagulation after isolated pulmonary embolism. Eur Respir J. 2016 May;47(5):1429-35. doi: 10.1183/13993003.01126-2015. Epub 2016 Feb 25.

  PMID: 26917615 DERIVED

• Palareti G, Cosmi B, Legnani C, Antonucci E, De Micheli V, Ghirarduzzi A, Poli D, Testa S, Tosetto A, Pengo V, Prandoni P; DULCIS (D-dimer and ULtrasonography in Combination Italian Study) Investigators. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood. 2014 Jul 10;124(2):196-203. doi: 10.1182/blood-2014-01-548065. Epub 2014 May 30.

  PMID: 24879813 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

platelet poor plasma and whole blood for Dna

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Interventions

fibrin fragment D; Fibrin Fibrinogen Degradation Products

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Fibrin; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Fibrinogen; Protein Precursors

Study Officials

• Gualtiero Palareti, MD

  St.Orsola Malpighi University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Gualtiero Palareti

Study Record Dates

• First Submitted: August 6, 2009
• First Posted: August 7, 2009
• Study Start: September 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2012
• Last Updated: March 19, 2021

Record last verified: 2021-03

Locations

IT (1)