Clinical Trial on Pulmonary Hypertension - Clinical Trials Registry

Study Overview

Status

Not yet recruiting

Conditions

Pulmonary Hypertension

Intervention / Treatment

Other

Detailed Description

Background. Pulmonary hypertension (PH) is a heterogeneous pathophysiological condition characterized by progressive pulmonary vascular narrowing that ultimately results in right-sided heart failure and eventually death or lung transplantation.

Pulmonary arterial hypertension (PAH, group 1 PH), PH associated to chronic respiratory diseases or hypoxia (CRDPH, group 3 PH) and chronic thromboembolic pulmonary hypertension (CTEPH, group 4) are subgroups of pulmonary hypertension.

The effectiveness of current pharmacological treatments is suboptimal and a large proportion of patients still had events or died despite receiving combination therapy. Vitamin D deficiency has been found to be much more frequent in PAH patients than in the general population or even compared to patients with other severe cardiovascular diseases. Our previous study (PMID: 32041235) showed that PAH deficiency has a negative prognostic impact in three subgroups of PAH (idiopathic, heritable and drug-induced). Animal studies support that vitamin D deficiency worsens PAH.

Serum samples are available from the Spanish Biobank of pulmonary hypertension in IDIBAPS (Hospital Clinic, Barcelona) which has collected and stored samples from Spanish PH patients since 2013. The samples are anonymized and linked to clinical data, which are recorded in the registries REHAP (group 1 and 4 PH) and REHAR (group 3 PH) and are continuously updated.

Biomarkers, including, but not limited, to 25-OH-vitamin D and iPTH, will be measured in the samples using commercial ELISA kits. These measured values will be related to the clinical variables. Patients will be classified according to the biomarker levels. The analysis of the Receiver operating characteristic (ROC) curve will be performed and the optimal cutoff values for biomarkers levels will be chosen based for each biomarker.

The main end-point of the study is to analyze whether the levels of a given serum biomarker predicts survival as analyzed by a Kaplan-Meier analysis and statistically compared using the log-rank test.

Secondary end-points. The Cox's proportional hazards model will be also used to include additional covariates. Additional variables that will be compared: 6-min walking distance, tricuspid annular plane systolic excursion (TAPSE), B-type natriuretic peptide (BNP) and the N-terminal fragment of pro-BNP (NT-pro-BNP) levels, New York Heart Association (NYHA) functional class, the non-invasive risk score (PMID: 28775050).

Two-sample comparisons will be analyzed using Mann-Whitney test for non normal continuous variables, t-test for normal continuous variables, and exact Fisher test or chi-square for trends for NYHA functional class or risk assessment. Data will be presented as scatter plots and medians. A p-value less than 0.05 will be considered statistically significant.

This is a collaborative study within the Ciberes Network Francisco Pérez Vizcaíno (Univ Complutense) Isabel Blanco (IDIBAPS) Rui Adao (Univ Complutense)

Study Type

Observational

Enrollment (Estimated)

345

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Francisco Perez Vizcaino, PhD, Full professor
Phone Number: 34-913941464
Email: fperez@med.ucm.es

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Patients diagnosed of PH (groups 1, 3 and 4) which have donated serum samples to the Spanish Biobank of PH. All these patients are included in the Spanish registries of PH (REHAP for groups 1 and 4, REHAR for group 3) Samples available in the Biobank from controls who have donated serum and have no known cardiovascular disease.

Description

Inclusion Criteria: Samples from patients with group 1, 3 or 4 PH stored in the Spanish PH Biobank (IdiBAPS). A maximum of 100 samples was limited for PAH associated to groups 1.1, 1.2 and 1.3 (idiopathic, heritable and drug-induced PH) and 100 samples from group 4. Samples will be randomly selected by the Biobank managers. All available samples from control (matched for sex and age) and group 3 PH.

Exclusion Criteria:

Samples from PAH associated to HIV infection, schistosomiasis or PAH with features of venous/capillary (PVOD/PCH) involvement.
Samples from patients that were analyzed in our previous study (PMID: 32041235)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Control 46 anonymized serum samples from controls without any known cardiovascular disease collected at the Biobank, matched by sex and age with the other cohorts. All the available samples were recruited. This group is used to compare the biomarker levels in healthy individuals.
Pulmonary arterial hypertension (group 1 PH) 170 anonymized serum samples from patients with pulmonary arterial hypertension, including patients with idiopathic PAH (87), heritable PAH (5), drug-induced PAH (8), PH associated to connective tissue disease (27), PH associated to portal hypertension (12), associated ot congenital heart disease (31). Samples were randomly selected by the Biobank administrators with the only condition that they had not been previously analyzed by us.
Chronic thromboembolic pulmonary hypertension (group 4 PH) 100 anonymized serum samples from patients with chronic thromboembolic pulmonary hypertension.
Pulmonary hypertension associated to Chronic Respiratory Disease or hypoxia (group 3 PH) 30 anonymized serum samples from patients with CRD-associated PH. All the available samples were recruited.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival Time Frame: Events (deaths) will be analyzed from the blood sample extraction until March 1st 2025.	The main end-point of the study is to analyze whether the levels of the serum biomarker predicts survival as analyzed by a Kaplan-Meier analysis and statistically compared using the log-rank test.	Events (deaths) will be analyzed from the blood sample extraction until March 1st 2025.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival (hazard risk) and transplant-free survival Time Frame: Events (death or transplant) will be analyzed from the blood sample extraction until March 1st 2025.	Survival will also be analyzed using the Cox's proportional hazards model to analyze potential co-variates. To analyze whether the levels of the serum biomarker predicts transplant-free survival as analyzed by a Kaplan-Meier analysis and statistically compared using the log-rank test.	Events (death or transplant) will be analyzed from the blood sample extraction until March 1st 2025.
Clinical risk factors Time Frame: Parameters will be obtained from the registry at the nearest date within six months of the date of plasma sampling in the Biobank	Additional variables that will be compared: 6-min walking distance, tricuspid annular plane systolic excursion (TAPSE), B-type natriuretic peptide (BNP), the N-terminal fragment of pro-BNP (NT-pro-BNP) levels, New York Heart Association (NYHA) functional class and the non-invasive risk score (PMID: 28775050). Two-sample comparisons will be analyzed using Mann-Whitney test for non normal continuous variables, t-test for normal continuous variables, and exact Fisher test or chi-square for trends for NYHA functional class or risk assessment. Data will be presented as scatter plots and medians. A p-value less than 0.05 will be considered statistically significant.	Parameters will be obtained from the registry at the nearest date within six months of the date of plasma sampling in the Biobank

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Complutense de Madrid

Collaborators

Hospital Clinic of Barcelona

Investigators

Principal Investigator: Francisco Perez Vizcaino, PhD, Universidad Complutense de Madrid

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2025

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

December 28, 2025

Study Registration Dates

First Submitted

March 3, 2025

First Submitted That Met QC Criteria

March 7, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)