Simplification of the Diagnosis of Deep Vein Thrombosis (PALLADIO)

Identification of the Optimal Approach to the Ultrasound Diagnosis of Deep Vein Thrombosis of the Lower Extremities in Symptomatic Patients

Prospective cohort study aimed at simplifying the diagnostic approach to symptomatic patients with the clinical suspicion of deep vein thrombosis (DVT) of the lower extremities. All patients will receive a pre-test clinical probability (PTP) and the determination of D-dimer. Patients with low PTP and negative D-dimer will have the diagnosis ruled out. All other patients will undergo compression ultrasonography (CUS) of the proximal vein system. Patients with negative CUS and either low PTP or negative D-dimer will have the diagnosis ruled out, while those with high PTP and positive D-dimer will undergo extensive ultrasound investigation of the calf vein system. All patients in whom the diagnosis of DVT is ruled out will be followed-up prospectively up to three months for documenting the development of symptomatic thromboembolic events.

Study Overview

• Status: Completed
• Conditions: Deep Venous Thrombosis
• Intervention / Treatment: Other: Extensive search for isolated calf DVT

Detailed Description

All eligible patients will undergo D-dimer measurement and a formal assessment of pre-test clinical probability (PTP) by means of the Wells score. Patients with unlikely PTP and negative D-dimer will have DVT ruled out and will undergo a 3-month clinical follow-up. If at least one of the two tests is positive, patients will undergo CUS of the proximal vein system by investigating at least the common femoral vein at the groin, the superficial femoral vein at the mid thigh and the popliteal vein(s) in the popliteal fossa. A positive CUS will adjudicate proximal DVT. In the case of negative CUS of the proximal vein system, patients with either negative D-dimer or unlikely PTP will have DVT ruled out, and will undergo a 3-month follow up. Only patients with concomitant likely PTP and positive D-dimer will undergo whole-leg ultrasonography with interrogation of the calf veins. A positive test will adjudicate distal DVT. Patients with negative test will undergo a 3-month clinical follow up.

Follow-up. All patients in whom DVT is ruled out will be monitored for 3 months (either by clinical visit or by telephone contact) after the enrolment in the study. Patients with clinical symptoms of DVT or PE during follow-up will undergo objective diagnostic testing (venous ultrasound for suspected DVT and spiral CT-scan or VQ scan for suspected PE). All source documents will be sent out for an independent adjudication. In case of death, PE diagnosis will be adjudicated by means of autopsy, if available. If autopsy is not available, the adjudication of PE-related death will be done based on clinical documentation.

D-dimer. All quantitative D-dimer tests available at each center will be acceptable for the purpose of this study. D-dimer will be considered negative according to the cut-offs provided by manufacturers.

Sample size. The investigators expect that in every 100 symptomatic outpatients DVT will be excluded without the need for objective testing in approximately 30%, while approximately 20% will have a CUS-detected proximal DVT, approximately 15% will have negative CUS and unlikely PTP in spite of positive D-Dimer (no need for further investigation), approximately 15% will have negative CUS and negative D-Dimer in spite of likely PTP (no need for further investigation, and approximately 20% will have negative CUS and both likely PTP and positive D-Dimer (thus requiring interrogation of the calf vein system).

The investigators hypothesize that the incidence of venous thromboembolic events during follow up in patients labeled as not having DVT will not exceed 1% with the application of the proposed algorithm, and that the upper limit of the 95% confidence intervals around this proportion will not exceed 2%. Accordingly, ap proximately 1100 patients should be enroled.

• Study Type: Interventional
• Enrollment (Actual): 1100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Padua, Italy, 35128
    • Paolo Prandoni

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:

• outpatients with clinically suspected DVT
• signed informed consent

Exclusion Criteria:

• concomitant signs or symptoms of pulmonary embolism
• previous DVT of the affected leg
• referral for superficial vein thrombosis or bilateral DVT
• ongoing or planned anticoagulant therapy
• need for pharmacological thromboprophylaxis (e.g. recent surgery or medical disease)
• inpatient status
• unavailability to follow up
• pregnancy
• age < 18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extensive search for isolated calf DVT; As this is a prospective cohort study, for definition there is only 1 arm	Other: Extensive search for isolated calf DVT; Extensive search for isolated calf DVT in patients with negative CUS of the proximal veins who have a high PTP and a positive D-dimer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of withdrawing anticoagulation from patients labeled as not having DVT on the basis of a one-day examination	To assess the rate of symptomatic thromboembolic events occurring up to 3 months after DVT exclusion	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of isolated calf vein thrombi	Patients with high PTP and positive D-dimer in spite of negative CUS of the proximal vein system will undergo extensive search for isolated calf vein DVT.	Up to 1 day

Collaborators and Investigators

• Sponsor: University of Padova
• Investigators: Study Chair: Paolo Prandoni, MD, PhD, University of Padua, Italy

Publications and helpful links

General Publications

• Ageno W, Camporese G, Riva N, Iotti M, Bucherini E, Righini M, Kamphuisen PW, Verhamme P, Douketis JD, Tonello C, Prandoni P; PALLADIO Study Investigators. Analysis of an algorithm incorporating limited and whole-leg assessment of the deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): a prospective, multicentre, cohort study. Lancet Haematol. 2015 Nov;2(11):e474-80. doi: 10.1016/S2352-3026(15)00190-8. Epub 2015 Oct 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: August 5, 2011
• First Submitted That Met QC Criteria: August 8, 2011
• First Posted (Estimate): August 9, 2011

Study Record Updates

• Last Update Posted (Estimate): January 26, 2015
• Last Update Submitted That Met QC Criteria: January 22, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Deep vein thrombosis; Pulmonary embolism; Ultrasonography; D-dimer; Pre-test probability
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: 2188P