Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03953560 |
| Other study ID # |
0034667956480 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 16, 2019 |
| Est. completion date |
February 15, 2022 |
Study information
| Verified date |
March 2022 |
| Source |
Hospitales Universitarios Virgen del Rocío |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Routine screening for Chronic thromboembolic pulmonary hypertension (CTEPH) i after PE is not
supported by current evidence and guidelines.
This study aims to evaluate if a screening program for patients with acute PE based on
telephone monitoring of symptoms and further examination if only symptomatic patients could
help an early detection of CTEPH.
Description:
Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication following
an acute or silent pulmonary embolism (PE). A history of acute PE was reported in 75% of
CTEPH patients. Nevertheless, incidence of CTEPH after a confirmed acute PE vary widely
depending of the studies, with estimated incidence from 0.5 to 4%. Performing a follow-up
examination of patients diagnosed with acute PE regardless of persisting symptoms and using
all available technical procedures is not cost-effective. As a consequence, routine screening
for CTEPH after PE is not supported by current evidence and guidelines.
CTEPH is a very disabling and mortal disease, although it is a potential curable disease.
However, delayed diagnosis and misdiagnosis is common. Patients are frequently diagnosed with
CTEPH at advanced stages of the disease leading to worse clinical outcomes. Early diagnosis
of CTEPH is essential, as delay in diagnosis may be associated with a worse prognosis, higher
perioperative mortality and inoperable diseases stages. Overall, evidence from various
sources suggests that early detection and treatment of CTEPH is advantageous in achieving
favorable clinical outcomes. Therefore, there is an important unmet need for early diagnosing
this disease.
Focusing diagnostic procedures only on symptomatic patients may be a practical approach for
detecting relevant CTEPH.
This study aims to evaluate if a screening program for patients with acute PE based on
telephone monitoring of symptoms and further examination if only symptomatic patients could
help an early detection of CTEPH.
Objectives
- Primary outcome: To estimate the impact of an easy and simple strategy to identify
CTEPH.
- Secondary outcomes:
- To identify patients with CTED after PE
- To obtain external validation from scores to identify patients at risk to develop
CTEPH
- To develop new score to identify high risk population to develop CTEPH
Hypothesis Conceptual hypothesis: The use of a strategy to detect CTEPH will increase number
of patients diagnosed of pulmonary hypertension.
Operational hypothesis: The use of a strategy to detect CTEPH will increase in a 200% the
number of patients diagnosed with CTEPH.
Design Cohorts study in consecutive patients with objectively confirmed PE.
Specialists implied Internal medicine, Pulmonologist, Hematologist from 20 hospitals.
Inclusion criteria: 1) Age > 18 year 2) Objectively confirmed diagnosis of acute PE by
multidetector CT, V/Q lung scan, or selective pulmonary angiography, according to established
diagnostic criteria, with or without symptomatic DVT, 3) Ability of subject to understand the
character and consequences of the study, 4) informed consent of the subject. Exclusion
criteria: refused informed consent, inability to cooperation.
Intervention Investigator from each center will recover consecutive PE patients and collect
baseline, demographic and co-morbidities.
In all patients enrolled in the study a short questionnaire regarding dyspnea symptoms will
be performed. All patients that refer dyspnea grade ≥ II according NYHA-WHO modified scale
will be cited as outpatient to be evaluated
A written informed consent will be required all patients evaluated in consultant.
Imaging studies and right heart catheterization is the procedure agreeing with the standard
care according to current ESC/ERS Guidelines.
In all patients, the following tests will be performed:
1. Pulsioximetry.
2. Electrocardiogram.
3. Blood sample with determination of NT-ProBNP.
4. Echocardiography. Only an echocardiography indicative of PH warrants further evaluation
5. V/Q scintigraphy. Possible CTEPH can be assumed when mismatched perfusion defects are
detected by VQ scan.
6. Right heart catheterization & Pulmonary CT Scan are required for confirming the
diagnosis
The relationship of Doppler echocardiography-estimated PASP with right heart catheterization
(RHC)-measured PASP was examined using Spearman's correlation coefficients. The Bland-Altman
method was then used to assess the agreement between Doppler echocardiography-estimated and
RHC measured PASP. Doppler echocardiography-estimated PASP within +/- 10mmHg of the value
measured on RHC was considered accurate, consistent with the cutoffs used in other
publications.
Secondary outcome include number of patients with chronic thromboembolic disease (CTED),
described as chronic thromboembolic pulmonary vascular obstruction with normal resting
pulmonary artery pressures.
Treatment: No treatment required
Statistical Plans Sample size calculation We estimate CTEPH prevalence in reference group of
1%, and a prevalence of CTEPH in interventional group of 2.8%. With unilateral test, con
confidence level of 95%, statistic power of 80% and losses expected of 25%, we calculated a
final sample size of 947.
The investigators calculate that 16-20 centers in Spain are needed to recruit patients
Investigators will compare baseline characteristics of patients with and without CTEPH using
chi-square tests for categorical variables and non-parametric rank tests for continuous
variables. Cumulative incidence of CTEPH will be estimated using the Kaplan-Meier technique.
To do external validation of previous score to predict CTEPH discriminative power by
calculating the area under the receiver-operating characteristic (ROC) curve will be done,
performing a non-parametric test of the equality of the areas under the ROC curves.
Goodness-of-fit of the score points for each score in a logistic regression model using
Pearson's chi-square test.
Student's t test and X2 test (or Fisher's exact test where appropriate) will be used to
compare continuous or categorical variables, and multivariable analysis through a logistic
regression model using the Wald method (step back) to identify independent predictors for the
occurrence of CTEPH. Covariates entering in the model will be selected by a significance
level of p <0.20 on univariable analysis, or by a well-known association reported in the
literature. Then, the investigators will build a prognostic score assigning points to each
independent variable according to regression coefficients β, rounding to the nearest integer.
The investigators will assign a risk score to each patient by adding up points for each
independent variable. Performance will be quantified in terms of calibration using the
Hosmer-Lemeshow test. Model discrimination will be assessed using the C-statistic. Internal
validity of the score will be confirmed using bootstrap analysis. For the statistical
analysis the investigators will use the IBM SPSS Statistics program (version 19; SPSS Inc.,
Chicago, IL), and a two-sided p<0.05 was considered to be statistically significant.
