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Trial record 3 of 33 for:    CTEPH | Recruiting, Not yet recruiting, Available Studies

Early Non-invasive Detection of CTEPH After Pulmonary Embolism (InShape2)

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ClinicalTrials.gov Identifier: NCT02555137
Recruitment Status : Recruiting
First Posted : September 21, 2015
Last Update Posted : September 7, 2016
Sponsor:
Information provided by (Responsible Party):
Leiden University Medical Center

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 2 years from the index PE diagnosis. During that period, the study protocol will not interfere with standard patient care, allowing diagnostic tests as deemed indicated by the treating physician including echocardiography in case of new respiratory symptoms. At the end of the follow-up period, all patients will be subjected to a second echocardiography that will be handled according to the above stated procedures to evaluate the presence of CTEPH.


Condition or disease Intervention/treatment
Chronic Thromboembolic Pulmonary Hypertension Other: 'prediction score' and 'rule-out criteria'

Detailed Description:

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 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 2 years from the index PE diagnosis. During that period, the study protocol will not interfere with standard patient care, allowing diagnostic tests as deemed indicated by the treating physician including echocardiography in case of new respiratory symptoms. At the end of the follow-up period, all patients will be subjected to a second echocardiography that will be handled according to the above stated procedures to evaluate the presence of CTEPH.


Study Type : Observational [Patient Registry]
Estimated Enrollment : 336 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: Early Non-invasive Detection of CTEPH After Pulmonary Embolism - The InShape-2 Study
Study Start Date : February 2016
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : December 2019


Group/Cohort Intervention/treatment
outcome cohort study
'prediction score' and 'rule-out criteria'
Other: 'prediction score' and 'rule-out criteria'
The combination of the 'prediction score' and the 'rule-out criteria' constitutes an accurate follow-up after PE aimed at diagnosing CTEPH in early stages.




Primary Outcome Measures :
  1. 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'.


Secondary Outcome Measures :
  1. 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

  2. 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. 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).

  4. 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.

  5. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive patients treated for objectivated symptomatic acute PE
Criteria

Inclusion Criteria:

  • All patients with an objectivated first or recurrent diagnosis of symptomatic acute PE, who have been treated for at least three months with therapeutically dosed anticoagulant therapy according to current guidelines;
  • Signed and dated informed consent of the subject available before the start of any specific study procedures;
  • Age ≥18 years;

Exclusion criteria:

  • Known CTEPH or PH;
  • Known (i.e. echocardiographic confirmed) NYHA class III or IV chronic heart failure due to left ventricular systolic dysfunction, left ventricular diastolic dysfunction or significant valvular lesions;
  • Severe renal failure (eGFR <15 ml/min) or renal replacement therapy;
  • Medical or psychological condition that would not permit completion of the study or signing of informed consent, including life expectancy less than six months, or unwillingness to sign informed consent;
  • Non-compliance or inability to adhere to treatment or to the follow-up visits.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02555137


Contacts
Contact: F.A. Klok, MD PhD 0031-71-5263761 f.a.klok@lumc.nl
Contact: M.V. Huisman, prof 0031-71-5263761 m.v.huisman@lumc.nl

Locations
Belgium
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: M. Delcroix, prof         
Netherlands
VUmc Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: A. Vonk Noordegraaf, prof         
Haga Recruiting
Den Haag, Netherlands, 2545 CH
Contact: A.T.A. Mairuhu, MD PHD         
LUMC Recruiting
Leiden, Netherlands, 2333ZA
Contact: Yvonne Ende-Verhaar, MD    0031715298096    y.m.ende-verhaar@lumc.nl   
Poland
medical university of Warsaw Recruiting
Warsaw, Poland
Contact: P Pruszczyk, prof         
Sponsors and Collaborators
Leiden University Medical Center
Investigators
Principal Investigator: F.A. Klok, MD PhD Department of Thrombosis and Hemostasis LUMC Leiden

Publications of Results:
Responsible Party: Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT02555137     History of Changes
Other Study ID Numbers: NL54450.058.15
First Posted: September 21, 2015    Key Record Dates
Last Update Posted: September 7, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Leiden University Medical Center:
chronic thromboembolic pulmonary hypertension
pulmonary embolism
pulmonary hypertension
screening
echocardiography

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Embolism
Pulmonary Embolism
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Embolism and Thrombosis