Early Non-invasive Detection of CTEPH After Pulmonary Embolism

NCT02555137 | Completed

• 1 other identifier: NL54450.058.15
• Study Type: observational
• Target: 424
• Locations: 3 countries
• Sites: 5

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.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Keywords

chronic thromboembolic pulmonary hypertension; pulmonary embolism; pulmonary hypertension; screening; echocardiography

Outcome Measures

Primary Outcomes (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'.

  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'.

  2-year follow-up

Secondary Outcomes (5)

• The cumulative incidence and incidence rate of CTEPH in the total study population with corresponding 95% confidence interval

  2-year follow-up

• 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

  2-year follow-up

• 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).

  2-year follow-up

• 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

  2-year follow-up

• 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.

  2-year follow-up

Study Arms (1)

outcome cohort study

'prediction score' and 'rule-out criteria'

Other: 'prediction score' and 'rule-out criteria'

Interventions

'prediction score' and 'rule-out criteria' OTHER

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.

outcome cohort study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients treated for objectivated symptomatic acute PE

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leiden University: lead

Study Sites (5)

UZ Leuven

Leuven, 3000, Belgium

Location

VUmc

Amsterdam, 1081 HV, Netherlands

Location

LUMC

Leiden, 2333ZA, Netherlands

Location

Haga

The Hague, 2545 CH, Netherlands

Location

medical university of Warsaw

Warsaw, Poland

Location

Related Publications (3)

• Klok FA, Tesche C, Rappold L, Dellas C, Hasenfuss G, Huisman MV, Konstantinides S, Lankeit M. External validation of a simple non-invasive algorithm to rule out chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Thromb Res. 2015 May;135(5):796-801. doi: 10.1016/j.thromres.2014.12.009. Epub 2014 Dec 13.

  PMID: 25746363 RESULT

• Klok FA, Surie S, Kempf T, Eikenboom J, van Straalen JP, van Kralingen KW, van Dijk AP, Vliegen HW, Bresser P, Wollert KC, Huisman MV. A simple non-invasive diagnostic algorithm for ruling out chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. Thromb Res. 2011 Jul;128(1):21-6. doi: 10.1016/j.thromres.2011.03.004. Epub 2011 Mar 30.

  PMID: 21450333 RESULT

• Fabyan KD, Holley AB. Postpulmonary embolism syndrome. Curr Opin Pulm Med. 2021 Sep 1;27(5):335-341. doi: 10.1097/MCP.0000000000000789.

  PMID: 34127618 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Hypertension

Study Officials

• F.A. Klok, MD PhD

  Department of Thrombosis and Hemostasis LUMC Leiden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: September 15, 2015
• First Posted: September 21, 2015
• Study Start: February 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 9, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); PL (1); BE (1)