Residual Pulmonary Vascular Obstruction Index Computed with Ventilation/perfusion SPECT/CT Imaging to Predict the Risk of Venous Thromboembolism Recurrence in Patients with Pulmonary Embolism (PRONOSPECT)

University Hospital, Brest665 enrolled

Overview

Major risk after pulmonary embolism (PE) is recurrence, fatal in 10% of patients. Patients with PE can be stratified in 3 groups according to the risk of recurrence : very low risk, high risk or Intermediate risk. Little is known about this last group. Anticoagulation is efficient to prevent recurrence but is currently not recommended for patient with an intermediate risk of recurrence. Identifying risk factors of recurrent PE remains a major issue to identify sub-groups of patients who would require lifelong anticoagulation. In 30-40% of cases, PE patients develop residual pulmonary vascular obstruction (RPVO), which has been found to be associated with an increased recurrence risk. This last observation was mostly reported in patients with unprovoked PE (patients with high risk of recurrence) and RPVO was measured using conventional planar lung scan. In patients with an intermediate risk of recurrence, the impact of RPVO has been much less studied. In addition, the definition of RPVO was variable according to studies and correlation between RPVO burden and recurrence risk has not been clearly demonstrated. This might be explained by the inherent limitation of RPVO quantification using conventional planar imaging, which is only based on a visual estimation on 2-dimensional images. Ventilation/Perfusion Single Photon Emission Computed Tomography (V/Q SPECT/CT) is a new method of scintigraphic image acquisition that offers the advantage of 3-dimensional imaging, enabling more accurate and reproducible quantification of RPVO. The main hypothesis of this study is that in patients with PE at intermediate risk of recurrence, RPVO computed with V/Q SPECT/CT imaging may be an important predictor of recurrence.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

665

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients ≥ 18 years, * who experienced an objectively proven PE, * who have been treated initially with anticoagulant therapy for 3 to 6 uninterrupted months (180 - 210 days) and for whom anticoagulation will not be prolonged. Exclusion Criteria: * Unwilling or unable to give written informed consent (protected adults, under tutorship or curatorship) * Patients deprived of their liberty by a judicial or administrative decision, patients undergoing psychiatric care by virtue of Articles L. 3212-1 and L. 3213-1 who are not covered by the provisions of Article L. 1121-8 and patients admitted to a health or social establishment for purposes other than research * No Social security affiliation * Isolated DVT * Pregnant women,parturients women * Other indication for anticoagulant therapy (e.g. atrial fibrillation, mechanic valve) * Life expectancy \< 6 months * Any patients for whom there is a strong indication to treat longer than 6 months: PE provoked by a major persistent factor (e.g. cancer) or Recurrent unprovoked PE * PE provoked by a major transient risk factor

Locations (13)

CHU Amiens

Amiens, France, France

ACTIVE_NOT_RECRUITING

CHU Angers

Angers, France, France

NOT_YET_RECRUITING

CHU Brest

Brest, France, France

RECRUITING

Hôpital Louis MourierAP-HP

Colombes, France, France

NOT_YET_RECRUITING

CHD Vendée - La Roche sur Yon

La Roche-sur-Yon, France, France

RECRUITING

Kremlin-Bicêtre AP-HP

Le Kremlin-Bicêtre, France, France

NOT_YET_RECRUITING

CH Les Sables d'Olonne

Les Sables-d'Olonne, France, France

NOT_YET_RECRUITING

Hegp Ap-Hp

Paris, France, France

NOT_YET_RECRUITING

CH Quimper

Quimper, France, France

RECRUITING

CHU St-Etienne

Saint-Etienne, France, France

NOT_YET_RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

Symptomatic recurrent venous thromboembolism (VTE), including objectively confirmed nonfatal symptomatic PE or proximal deep vein thrombosis or fatal PE during a 24-month follow-up after inclusion in the study

In case of a suspected VTE or death during follow-up, the study personnel will collect related clinical data on the electronic case report form, and prepare an adjudication file, including symptoms, clinical notes, hospital discharge summary, and results of all diagnostic tests. All suspicion of VTE recurrence will be adjudicated blindly by an independent central Clinical Events Committee. To assess the primary objective, RPVO will be defined by a perfusion mismatched defect of at least 5% of the whole lung, corresponding to a segmental defect. SPECT imaging should not be used at inclusion and should not result in proposing prolonged anticoagulation. SPECT images will be numerically stored and interpretation will be later performed independently by two nuclear medicine physicians who will be blinded to clinical history and the patient's outcome. Any difference in interpretation will be resolved by consensus.

Time frame: From baseline to Month 24

Secondary Outcomes

Adjudicated symptomatic objectively confirmed recurrent VTE during the follow-up period.

Time frame: From baseline to Month 24

Percentage of patients with RPVO (as defined by a perfusion defect > 5%) on V/Q SPECT/CT imaging at inclusion in the study.

Time frame: Inclusion

Different cut-offs of pulmonary vascular obstruction index will be evaluated to predict the risk of VTE recurrence at 2 years, by generating ROC curves

Time frame: Inclusion

Other predictors of adjudicated symptomatic objectively confirmed recurrent VTE at 2 years including: age

Time frame: Inclusion

The following score will be computed : HERDOO2 (Hyperpigmentation, Edema, Redness, D-Dimer, Obesity, Old)

Prediction score of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism recurrence in patients with unprovoked PE, (test in patients at intermediate risk of recurrence in this trial). Patient with score of 0 to 1 have a low risk of recurrent VTE, whereas patient with a score of at least 2, have a high risk of recurrence

Time frame: Inclusion

Potential predictors of RPVO including : demographics

Time frame: Inclusion

Symptomatic recurrent VTE during a 3 Months follow-up period in patients with suspicion of PE recurrence who has been left untreated based on a negative V/Q SPECT/CT scan

Symptomatic recurrent VTE including objectively confirmed nonfatal symptomatic PE or proximal DVT or fatal VTE

Time frame: 3 Months follow-up period after the suspicion of PE recurrence

Dyspnea index will be assessed using mMRC scale (Modified Medical Research Council)

The mMRC scale is a self-assessment tool used to measure the level of impairment caused by breathlessness during daily activities, rated on a scale from 0 to 4.\[2\] 0, no breathlessness except on strenuous exercise and 4, too breathless to leave the house, or breathless when dressing or undressing.

Time frame: Inclusion and Month 6

Quality of life (QoL) will be assessed using PEmb-Qol (Pulmonary Embolism Quality of Life)

The PEmb-QoL is a validated 40-item questionnaire to quantify health-related quality of life in patients having experienced pulmonary embolism (PE). It covers six health dimensions: frequency of complaints, activities of daily living limitations, work-related problems, social limitations, intensity of complaints, and emotional complaints.The PEmb-QoL dimension scores are calculated by taking the mean of the constituting items. Dimension scores are then transformed to a scale from 0-100 to make them comparable across dimensions, with higher scores indicating worse outcome.

Time frame: Inclusion and Month 6

Number of Participants with chronic thromboembolic pulmonary hypertension (CTEPH).

CTEPH will be defined by a mean pulmonary artery pressure \>20 mmHg.

Time frame: From baseline to Month 24

Mortality of all causes.

Time frame: From baseline to Month 24

Percentage of patients with RPVO (> 5%) on V/Q SPECT/CT imaging using Technegas and Krypton.

Time frame: Inclusion

The following score will be computed : PADIS-PE score.

PADIS-PE (score derived from the PADIS study : Prolonged Anticoagulation During eighteen months versus placebo after Initial Six-month treatment for a first episode of idiopathic Pulmonary Embolism randomized trial). A higher score indicates a higher risk of recidive.

Time frame: Inclusion

Other predictors of adjudicated symptomatic objectively confirmed recurrent VTE at 2 years including: gender

Time frame: Inclusion

Other predictors of adjudicated symptomatic objectively confirmed recurrent VTE at 2 years including: obesity

Body Mass Index \> 30 kg/m2

Time frame: Inclusion

Other predictors of adjudicated symptomatic objectively confirmed recurrent VTE at 2 years including: D-Dimer

Measurement of the concentration of plasma D-dimer

Time frame: Inclusion

Other predictors of adjudicated symptomatic objectively confirmed recurrent VTE at 2 years including: inherited or acquired thrombophilia

Number of Participants with inherited or acquired thrombophilia

Time frame: Inclusion

Other predictors of adjudicated symptomatic objectively confirmed recurrent VTE at 2 years including: residual vein thrombosis

Number of Participants with residual vein thrombosis

Time frame: Inclusion

Residual Pulmonary Vascular Obstruction Index Computed with Ventilation/perfusion SPECT/CT Imaging to Predict the Risk of Venous Thromboembolism Recurrence in Patients with Pulmonary Embolism (PRONOSPECT)

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts