Multicenter Study on the Development of Pulmonary Arterial Hypertension Screening Models Based on Artificial Intelligence for Patients With Systemic Sclerosis

NCT07236970 | Recruiting

• 2 other identifiers: 25/046_ARENASPI24/1880
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 5

Brief Summary

Pulmonary Arterial Hypertension (PAH) is a rare and severe condition that can be associated with Systemic Sclerosis (SSc), significantly worsening the prognosis of the latter disease. Screening programs based on clinical, laboratory, pulmonary function test, electrocardiographic, and echocardiographic data have been shown to enable earlier diagnosis and improve the prognosis of PAH associated with SSc. However, the hemodynamic criteria for the diagnosis of PAH have recently changed, and the usefulness of these screening programs in this new context is unknown. The primary objective of this study is to develop a PAH screening program in patients with SSc through the use of different artificial intelligence algorithms, comparing these algorithms with classical screening programs. These algorithms will be externally validated in different hospitals in Spain. As secondary objectives, the study will assess the usefulness of various proteins involved in the metabolic pathways related to the development of PAH, as well as certain parameters of right ventricular function and measures of quality-of-life impact, in the prognostic evaluation of PAH associated with SSc. To this end, simple and reproducible clinical data will be used, such as electrocardiogram, echocardiogram, and different quality-of-life scales obtained from major PAH and SSc registries. Machine learning techniques and Bayesian networks will be applied to generate artificial intelligence models for screening and prognostic assessment.

Conditions

Pulmonary Hypertension; Systemic Sclerosis (SSc); Systemic Sclerosis-Associated PAH

Keywords

Pulmonary Hypertension; Systemic Sclerosis; algorhythm; artificial intelligence; machine learning

Outcome Measures

Primary Outcomes (3)

• Diagnostic accuracy of AI-based screening models for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc)

  Sensitivity, specificity, and area under the ROC curve (AUC) of machine learning and Bayesian network-based algorithms compared with classical screening algorithms, using right heart catheterization as the diagnostic gold standard.

  At baseline (cross-sectional assessment at study entry)

• Event-free survival in patients with systemic sclerosis-associated PAH

  Time to first clinical event defined as all-cause mortality, hospitalization due to PAH, or clinical worsening (progression of WHO functional class, decline in 6-minute walk distance, or worsening hemodynamics).

  Up to 24 months of follow-up

• Patient-reported quality of life in systemic sclerosis-associated PAH

  Change in quality-of-life scores measured with validated questionnaires from baseline to follow-up.

  Baseline and 24 months

Secondary Outcomes (10)

• Correlation of circulating activina A with event-free survival in SSc-PAH

  From baseline to 24 months.

• Correlation of circulating activina B with event-free survival in SSc-PAH

  From baseline to 24 months

• Correlation of circulating inhibina alfa with event-free survival in SSc-PAH

  From baseline to 24 months

• Correlation of circulating follistatin with event-free survival in SSc-PAH

  From baseline to 24 months

• Correlation of circulating FSTL3 with event-free survival in SSc-PAH

  From baseline to 24 months

Study Arms (3)

Cohort 1

Development cohort for an AI model based on widely available clinical data. 300 controls with Systemic Sclerosis (SSc) without Pulmonary Hypertension (PAH) and 50 cases of SSc with PAH

Cohort 2

External validation of the screening model: 200 controls with SSc without PAH and 50 cases with PAH associated with SSc

Cohort 3

Prognostic models including protein analysis, cardiac imaging, PREMS and PROMS: 100 patients with PAH-SSc

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with systemic sclerosis (SSc), with and without pulmonary arterial hypertension (PAH), recruited from the Spanish national PAH registry (REHAP), the systemic sclerosis registry at the Rheumatology Department, and the CSUR national referral unit for pulmonary hypertension at Hospital Universitario 12 de Octubre, as well as participating centers. Cohort 1 (development cohort): 300 SSc patients without PAH and 50 SSc patients with confirmed PAH, retrospectively selected from 2016 to 2024. Cohort 2 (external validation cohort): 200 SSc patients without PAH and 50 with PAH-SSc, prospectively recruited from participating centers and REHAP during the first 2 years of the study. Cohort 3 (prognostic cohort): 100 patients with PAH-SSc prospectively recruited from REHAP and participating centers between January 2025 and December 2026.

You may qualify if:

• Age ≥ 18 years
• Clinical diagnosis of systemic sclerosis (SSc) according to ACR/EULAR criteria
• For controls (SSc without PAH): absence of pulmonary arterial hypertension; patients with isolated or combined post-capillary pulmonary hypertension (pulmonary capillary pressure \> 15 mmHg) or Group 3 pulmonary hypertension may be included, limited to 20% of this group
• For cases (SSc-associated PAH): confirmed PAH by right heart catheterization (mean pulmonary arterial pressure \> 20 mmHg, pulmonary capillary pressure \< 15 mmHg, pulmonary vascular resistance \> 2 Wood Units)

You may not qualify if:

• Missing data in the main variables at diagnosis (clinical assessment, blood tests, electrocardiogram, transthoracic echocardiogram).
• Inability to provide informed consent

Sponsors & Collaborators

• Alejandro Cruz Utrilla: lead

Study Sites (5)

Hospital Universitario Clínico San Cecilio

Granada, Andalusia, 18007, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

MeSH Terms

Conditions

Hypertension, Pulmonary; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Cardiologist Consultant in the Pulmonary Hypertension Unit, Principal Investigator

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: November 19, 2025
• Study Start: May 30, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

ES (5)