Clinical Trial: Early Non-invasive Detection of CTEPH After Pulmonary Embolism

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Early Non-invasive Detection of CTEPH After Pulmonary Embolism - The InShape-2 Study

Brief Summary:

This is a prospective, international, multicenter outcome cohort study. This study starts at the moment patients visit the outpatient clinic 3 to 6 months after a diagnosis of acute PE as part of routine medical care. If patients consent to study participation, the CTEPH clinical prediction score will be calculated. CTEPH is considered to be not present in patients with a low probability (≤6 points) and no symptoms suggestive of CTEPH, i.e. dyspnea on exertion, edema, newly developed palpitations, syncope or chest pains.The remaining patients with either high probability (>6 points) or who report symptoms that may be associated with CTEPH will be subjected to the 'rule-out criteria'. CTEPH will be assumed not present in patients with an age- and gender dependent normal NT-proBNP level (as defined by the assay's manufacturer), in the absence of any of the 3 ECG criteria. Patients who have an abnormal result from the 'rule-out criteria' will be referred for transthoracic echocardiography. All echocardiograms will be performed according to a predefined standardized protocol.

In case of echocardiographic intermediate or high probability of PH, patients will be referred for further diagnostic work-up of suspected CTEPH starting with perfusion lung scan or VQ-scan and right heart catheterization, of which the results will be discussed by an independent interdisciplinary working group of PH specialists, to ensure optimal diagnostic management. This latter diagnostic work-up of an abnormal echocardiograph lies within the setting of standard medical care.

All patients who were not diagnosed with pulmonary hypertension of any origin, or with NYHA class III or IV heart failure due to left ventricular systolic dysfunction, left ventricular diastolic dysfunction or significant valvular lesions, will be followed for a total of

Detailed Summary:

This is a prospective, international, multicenter outcome cohort study. This study starts at the moment patients visit the outpatient clinic 3 to 6 months after a diagnosis of acute PE as part of routine medical care. If patients consent to study participation, the CTEPH clinical prediction score will be calculated. This score consists of 6 variables that should be assessed at the time of PE diagnosis: unprovoked PE (+6 points), known hypothyroidism (+3 points), diagnostic delay >2 weeks (+3 points), right ventricular dysfunction on computed tomography pulmonary angiography (CTPA) or echocardiography (+2 points), known diabetes mellitus (-3 points) and thrombolytic therapy or embolectomy for the acute PE event (-3 points) CTEPH is considered to be not present in patients with a low probability (≤6 points) and no symptoms suggestive of CTEPH, i.e. dyspnea on exertion, edema, newly developed palpitations, syncope or chest pains. The remaining patients with either high probability (>6 points) or who report symptoms that may be associated with CTEPH will be subjected to the 'rule-out criteria'. CTEPH will be assumed not present in patients with an age- and gender dependent normal NT-proBNP level (as defined by the assay's manufacturer), in the absence of these 3 ECG criteria: 1) rSR' or rSr' pattern in lead V1, 2) R:S >1 in lead V1 with R >0.5mV and 3) QRS axis >90o. Patients who have an abnormal result from the 'rule-out criteria' will be referred for transthoracic echocardiography. All echocardiograms will be judged by the echocardiographic criteria for suspected PH according to the 2015 ESC guidelines.

In case of echocardiographic intermediate or high probability of PH, patients will be referred for further diagnostic work-up of suspected CTEPH starting with perfusion lung scan or VQ-scan and right heart catheterization, of which the results will be di
Sponsor: Leiden University Medical Center

Current Primary Outcome: The accuracy of the screening algorithm to detect CTEPH, as reflected by the 2-year incidence of confirmed CTEPH in patients in whom CTEPH was initially considered not present based on the 'risk stratification score' and the 'rule out criteria'. [ Time Frame: 2-year follow-up ]

The primairy endpoint is to evaluate the diagnostic accuracy of a CTEPH screening program based on the 'risk stratification score' and the 'rule out criteria'.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The cumulative incidence and incidence rate of CTEPH in the total study population with corresponding 95% confidence interval [ Time Frame: 2-year follow-up ]
    The cumulative incidence and incidence rate of CTEPH in the total study population will be calculated with corresponding 95% confidence interval
  • Feasibility of the screening algorithm, the number of necessary echocardiograms at baseline and the number of relevant echocardiographic findings at baseline, i.e. those that require treatment [ Time Frame: 2-year follow-up ]
    number of necessary echocardiograms at baseline and the number of relevant echocardiographic findings at baseline, i.e. those that require treatment
  • 3 Cost-effectiveness of the screening algorithm: a study-based cost-effectiveness analysis (CEA: diagnostic costs per early CTEPH diagnosis) and a model-based cost-utility analysis (CUA: societal costs per QALY). [ Time Frame: 2-year follow-up ]
    cost-effectiveness of the strategy for standardized follow-up after PE aimed at diagnosing CTEPH in early stages.The economic evaluation will include a study-based cost-effectiveness analysis (CEA: diagnostic costs per early CTEPH diagnosis) and a model-based cost-utility analysis (CUA: societal costs per QALY).
  • incremental diagnostic accuracy of electrocardiographically derived ECG-vectoranalysis on top of the manual ECG assessment by comparing the c-statistics and reclassification numbers between the manually and automatically assessed ECG parameters [ Time Frame: 2-year follow-up ]
    The additional diagnostic accuracy of the electrocardiographically derived ECG-VCG will be assessed by comparing the c-statistics and reclassification numbers between the manually and automatically assessed ECG parameters in the algorithm.
  • Inter-observer variability in the measurement of the RV/LV ratio on computed tomography pulmonary angiography (CTPA) expressed as the kappa-value of the ventricular dimension measurements by two independent researchers. [ Time Frame: 2-year follow-up ]
    Determination of the inter-observer variability in the measurement of the RV/LV ratio on computed tomography pulmonary angiography (CTPA).


Original Secondary Outcome: Same as current

Information By: Leiden University Medical Center

Dates:
Date Received: September 15, 2015
Date Started: February 2016
Date Completion: December 2019
Last Updated: September 6, 2016
Last Verified: September 2016