Right Heart and Lung Blood Flow During Exercise (RIGHT-NET 2.0) (RIGHT-NET 2)

September 25, 2026 updated by: Marco Salvatore, IRCCS SYNLAB SDN

The Right Heart International NETwork 2.0 (RIGHT-NET 2.0)

RIGHT-NET 2.0 is a multicenter observational study with a retrospective-prospective design that builds on the original RIGHT-NET study. It aims to observe and document the functional status of the right heart-pulmonary circulation unit (RH-PCU) at rest and during exercise stress transthoracic echocardiography (ExTTE) in clinically stable patients referred to cardiology, internal medicine, echocardiography, and exercise testing laboratories. The study will also include healthy volunteers, individuals with cardiovascular risk factors but no overt disease, athletes undergoing sports eligibility evaluation, and healthy individuals living at high altitude. Patients will be classified according to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The study plans to enroll at least 1000 additional subjects beyond the original RIGHT-NET cohort of 1000 participants, for a total anticipated enrollment of approximately 2000 subjects across 22 Italian and 16 international centers. Data will be collected through the REDCap electronic data capture platform in a pseudonymized format.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

The clinical and instrumental assessment of the right heart-pulmonary circulation unit is an essential step in the diagnostic, prognostic, and therapeutic algorithm of cardiorespiratory diseases. The original RIGHT-NET study demonstrated the relevance of physiological versus pathological responses through evaluation of the TAPSE/sPAP ratio and mPAP/CO slope during exercise stress echocardiography, both of which carry prognostic significance and predict all-cause mortality across healthy subjects, athletes, high-altitude residents, and patients with cardiopulmonary disease.

Study objectives include advancing understanding of RH-PCU physiology and pathophysiology during exercise, assessing the discriminative capacity of TAPSE/sPAP and mPAP/CO slope across clinical conditions, investigating associations between RH-PCU functional indices and short-, medium-, and long-term clinical outcomes including all-cause mortality, refining diagnostic and prognostic thresholds in line with the 2022 ESC/ERS guidelines, and building a standardized dataset via REDCap.

For each participant, demographic, anthropometric, and clinical characteristics will be collected, together with laboratory tests, invasive and non-invasive diagnostic procedures (including right heart catheterization, cardiac MRI, nuclear diagnostics, and arterial blood gas analysis), therapy data, and clinical outcomes. Data will be analyzed using R (version >= 4.3.1) with descriptive statistics, group comparisons, univariate and multivariate regression models, and supervised machine learning techniques (random forest, gradient boosting, support vector machine) for predictive modeling.

As an observational study, participation does not alter the participant's diagnostic or therapeutic pathway, and no additional insurance coverage beyond standard clinical practice is required.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2000

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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients referred, as part of their routine clinical pathway, to cardiology, internal medicine, echocardiography, or exercise testing (ergometry) laboratories at the participating centers, selected based on a documented clinical indication for right heart-pulmonary circulation unit assessment as determined by the referring physician, and classified according to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The population also includes healthy volunteers, including individuals undergoing occupational fitness assessment; individuals with cardiovascular risk factors but no overt cardiopulmonary disease; athletes referred for sports eligibility evaluation; and healthy individuals living at high altitude.

Description

Inclusion Criteria

  • Patients referred as part of their routine clinical pathway for evaluation in cardiology, internal medicine, echocardiography, or exercise testing laboratories, with a documented clinical indication for assessment of right heart-pulmonary circulation unit function, as determined by the referring physician
  • Classified according to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
  • Healthy volunteers, including individuals undergoing occupational fitness assessment
  • Individuals with cardiovascular risk factors but no overt cardiopulmonary disease
  • Athletes referred for sports eligibility evaluation
  • Healthy individuals living at high altitude
  • Clinically stable at the time of enrollment
  • Provision of consent to the processing of personal data in anonymous and aggregated form

Exclusion Criteria

  • Active oncological disease
  • Clinical conditions incompatible with the execution of exercise stress echocardiography (e.g., inability to perform physical exercise, severe musculoskeletal limitations, unstable angina, recent acute myocardial infarction, uncontrolled arrhythmias)
  • Current pregnancy
  • Any other condition judged by the referring physician to be incompatible with participation in the study

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

  • Observational Models: COHORT
  • Time Perspectives: OTHER

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Patients with Clinical Indication for RH-PCU Assessment

Patients referred, as part of their routine clinical pathway, to cardiology, internal medicine, echocardiography, or exercise testing laboratories for evaluation of right heart-pulmonary circulation unit function, based on a documented clinical indication as determined by the referring physician. Patients are classified according to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Intervention/exposure of interest: rest and exercise stress transthoracic color-Doppler echocardiography (ExTTE); additional non-invasive and invasive diagnostic procedures (right heart catheterization, cardiac MRI, nuclear diagnostics, arterial blood gas analysis) are performed where clinically indicated, as part of standard care.
Healthy Volunteers

Healthy individuals enrolled as volunteers or referred for assessment of fitness for work, with no known cardiopulmonary disease. Intervention/exposure of interest: rest and exercise stress transthoracic echocardiography (ExTTE), performed as part of the study assessment.
Subjects with Cardiovascular Risk Factors

Individuals presenting cardiovascular risk factors (e.g. hypertension, dyslipidemia, obesity, diabetes) but without overt cardiovascular or respiratory disease. Intervention/exposure of interest: rest and exercise stress transthoracic echocardiography (ExTTE), performed as part of the study assessment.
Athletes Undergoing Sports Eligibility Evaluation

Athletes referred to participating centers for evaluation of fitness for competitive or amateur sports activity. Intervention/exposure of interest: rest and exercise stress transthoracic echocardiography (ExTTE), performed as part of the study assessment.
Healthy Subjects Living at High Altitude

Healthy individuals residing at high altitude, included to characterize right heart-pulmonary circulation unit adaptation to chronic hypoxic exposure. Intervention/exposure of interest: rest and exercise stress transthoracic echocardiography (ExTTE), performed as part of the study assessment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
TAPSE/sPAP ratio at rest and during exercise stress echocardiography
Time Frame: Baseline

Tricuspid annular plane systolic excursion / systolic pulmonary artery pressure (TAPSE/sPAP) ratio, calculated by resting nd during exercise stress echocardiography as a non-invasive index of right ventricular-pulmonary arterial coupling.
Baseline
mPAP/CO slope at rest and during exercise stress echocardiography
Time Frame: Baseline

Slope of the relationship between mean pulmonary artery pressure (mPAP) and cardiac output (CO), derived at rest and during incremental exercise stress echocardiography as a non-invasive index of pulmonary vascular function.
Baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of the composite outcome of all-cause mortality or hospitalization for heart failure at follow-up
Time Frame: 1 year

Number of participants experiencing the composite outcome of death from any cause or hospitalization for left or right heart failure, analyzed in relation to baseline right heart-pulmonary circulation unit (RH-PCU) functional indices.
1 year
Area under the ROC curve (AUC) of the TAPSE/sPAP ratio for predicting the composite outcome of all-cause mortality or hospitalization for heart failure, compared with 2022 ESC/ERS Guideline risk-stratification thresholds
Time Frame: 1 Year

Receiver operating characteristic (ROC) curve analysis of the resting TAPSE/sPAP ratio, assessing its diagnostic and prognostic discriminative ability for the long-term composite outcome (Outcome 3), and refinement of cut-off values relative to the risk-stratification thresholds defined in the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.
1 Year
Area under the ROC curve (AUC) of the mPAP/CO slope for predicting the composite outcome of all-cause mortality or hospitalization for heart failure, compared with 2022 ESC/ERS Guideline risk-stratification thresholds
Time Frame: 1 Year

Receiver operating characteristic (ROC) curve analysis of the mPAP/CO slope during exercise stress echocardiography, assessing its diagnostic and prognostic discriminative ability for the long-term composite outcome (Outcome 3), and refinement of cut-off values relative to the risk-stratification thresholds defined in the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.
1 Year

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS SYNLAB SDN

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of Graz
University of Pisa
Federico II University
Azienda Sanitaria Universitaria Friuli Centrale
University of Trieste
University of Padova
Medical University of Lodz
Ohio State University
University Of Perugia
University Hospital Heidelberg
University of Milan
Universitat Politècnica de Catalunya
IRCCS Multimedica
CRO "Centro Clinical Trials" IRCCS Ospedale Policlinico San Martino
Fondazione IRCCS Policlinico San Matteo di Pavia
Cardio-Thoracic-Vascular Department. University Hospital San Giovanni di Dio e Ruggi d'Aragona. Salerno
Umberto I Hospital, Nocera Inferiore
University of Molise
Institute of Family Medicine, University of Szeged, Hungary
Cardarelli Hospital
IRCCS Ospedale San Raffaele
ASST Grande Ospedale Metropolitano Niguarda
Azienda Ospedaliera dei Colli
Jewish General Hospital (Montreal, Quebec, Canada)
Institute of Clinical Physiology, CNR, Pisa

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marco Salvatore, MD,PhD, IRCCS SYNLAB SDN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2027

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2036

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 18, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 1, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • n . 2/25 OSS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings