Clinical trial NCT06872710: Prognostic Value of Vitamin D and Intact Parathyroid Hormone (iPTH) in Pulmonary Hypertension
Official title: Prognostic Value of Vitamin D and IPTH in Pulmonary Hypertension
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Pulmonary Hypertension
Keywords: Vitamin D
iPTH
hyperparathyroidism
Lead sponsor: Universidad Complutense de Madrid
Sponsor class: OTHER
Collaborators: name: Hospital Clinic of Barcelona
First posted: 2025-03-12
Enrollment: 345
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
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.

Brief summary: The aim of this observational study is to analyse the prognostic value of 25(OH)-vitamin D, iPTH and other serum biomarkers in patients with pulmonary hypertension.

Serum samples are obtained from the Spanish Biobank of pulmonary hypertension. Clinical data will be collected from the Spanish registries on pulmonary hypertension (REHAP and REHAR).

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)

Eligibility criteria: 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:

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

Primary outcomes:
measure: Survival
timeFrame: Events (deaths) will be analyzed from the blood sample extraction until March 1st 2025.
Secondary outcomes:
measure: Survival (hazard risk) and transplant-free survival
timeFrame: Events (death or transplant) will be analyzed from the blood sample extraction until March 1st 2025.
measure: Clinical risk factors
timeFrame: Parameters will be obtained from the registry at the nearest date within six months of the date of plasma sampling in the Biobank
Other outcomes:
Locations:
Study officials:
affiliation: Universidad Complutense de Madrid
name: Francisco Perez Vizcaino, PhD
role: PRINCIPAL_INVESTIGATOR
References: