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)

Official title

Residual Pulmonary Vascular Obstruction (RPVO) Index Computed With Ventilation/Perfusion SPECT/CT Imaging to Predict the Risk of Venous Thromboembolism (VTE) Recurrence in Patients With Pulmonary Embolism (PE)

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.

Interventions

• Other Ventilation/Perfusion Single Photon Emission Computed Tomography (V/Q SPECT/CT)
  All patients will undergo a V/Q SPECT/CT scan at inclusion.

Primary outcome measures

• 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 [Time frame: From baseline to Month 24]

Secondary outcome measures (12)

• 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) [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 [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) [Time frame: Inclusion and Month 6]
• Quality of life (QoL) will be assessed using PEmb-Qol (Pulmonary Embolism Quality of Life) [Time frame: Inclusion and Month 6]
• Number of Participants with chronic thromboembolic pulmonary hypertension (CTEPH). [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]

Eligibility criteria

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 and parturients
• 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)
• Recurrent unprovoked PE

PE provoked by a major transient risk factor (e.g. surgery with general anesthesia for greater than 30 min, confined to bed in hospital for at least 3 days with an acute illness, cesarean section)

AND none of the following persistent factors :

• BMI ≥ 30
• Chronic respiratory disease
• Chronic inflammatory disease (e.g., ulcerative colitis, rheumatoid arthritis, etc.)
• Hepatocellular insufficiency
• Renal insufficiency with creatinine clearance < 60 mL/min
• Chronic or persistent immobilization

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

France · 13 centers

• CHU Amiens — Amiens
• CHU Angers — Angers
• CHU Brest — Brest
• Hôpital Louis MourierAP-HP — Colombes
• CHD Vendée - La Roche sur Yon — La Roche-sur-Yon
• Kremlin-Bicêtre AP-HP — Le Kremlin-Bicêtre
• CH Les Sables d'Olonne — Les Sables-d'Olonne
• Hegp Ap-Hp — Paris
• … and 5 more centers

Identifiers

NCT: NCT06372730 · 29BRC23.0161 · 2023-A01566-39

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗