A Study for the Identification of Biomarker Signatures for Early Detection of Pulmonary Hypertension (PH)

Study Overview
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Brief Summary
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The primary purpose of this study is to identify and develop biomarker signatures based on circulating micro ribonucleic acid (RNA) in the blood samples associated with high risk of pulmonary hypertension (PH) to assist in the diagnosis of PH; to estimate the sensitivity, specificity, positive predictive value, and negative predictive value of the biomarker signatures in identifying participants with PH by comparing the biomarker signatures to right heart catheterization (RHC) and to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the biomarker signatures with the sensitivity, specificity, positive predictive value, and negative predictive value of transthoracic echocardiogram (TTE) in identifying participants with PH documented by RHC.

Official Title
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A Prospective, Multicenter Study for the Identification of Biomarker Signatures for the Early Detection of Pulmonary Hypertension (PH)

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Other: Blood Sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having undergone an right heart catheterization (RHC) within 18 months (prevalent PH participants) or 6 months (prevalent non-PH participants) or have undergone or planned RHC within 6 weeks (incident participants). The results of the incident RHC (incident participants) or the most recent RHC (prevalent participants) will be used to classify the participant in one of the above study population categories Medically stable on the basis of physical examination, medical history and vital signs performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator Must provide an Informed Consent Form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study Must provide a separate informed consent (or their legally-acceptable representative must sign) if he or she agrees to provide an optional (deoxyribonucleic acid [DNA]) sample for research (where local regulations permit). Refusal to give consent for the optional (DNA) research sample does not exclude a participant from participation in the study Exclusion Criteria: Participants requiring renal dialysis History of lung or heart transplant (waiting list status or consideration of enlisting is allowed) Severe left ventricular dysfunction: Left ventricular ejection function less then (<) 35 percent (%)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Participants with PH and non-PH<br>Blood samples will be collected for biomarker analysis from new (incident) and existing (prevalent) participants who undergo right heart catheterization (RHC). Participants will be categorized into non-PH or PH based on the results of the RHC and those who are found to have PH will be further classified into the different groups of PH. A transthoracic echocardiography (TTE) will be performed if not done previously. | Other: Blood Sample<br>* Prevalent (existing) and incident (new) participants who are found to either have PH or not by RHC will provide blood sample for the establishment of a biomarker signature of PH.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression Levels of miRNAs Biomarkers | Blood samples will be collected for micro Ribonucleic acid (miRNA) assay by qPCR to identify a biomarker signature for the early detection of pulmonary hypertension (PH). | Day 1 | 
| Biomarker signatures for miRNA | Blood will be collected for miRNA to identify a biomarker signature(s) for detection of participants at high risk of PH. | Day 1 | 
| Biomarker Signature Performance in Identifying Participants with PH | Biomarker signature performance will be evaluated by estimating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the biomarker signatures documented by RHC for identifying participants with PH. | Day 1 | 
| Comparison of Performance of Biomarker Signatures and Transthoracic Echocardiogram (TTE) Based on Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value | The performance of the biomarkers signatures will be compared to the performance of TTE to identify participants with PH documented by RHC via sensitivity, specificity, positive predictive value, and negative predictive value. The sensitivity/specificity of the tests will be compared using McNemar's test. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under ROC Curve in Participants with PH who are Receiving Therapies Versus not Receiving drug Therapy | Performance of the biomarker signatures will be assessed using ROC curve in participants with PH who are receiving pulmonary arterial hypertension-specific drug therapies versus participants who are not receiving any drug therapy. | Day 1 | 
| Area Under ROC Curve in Participants with PAH, CTEPH, Isolated pre-Capillary and post-Capillary PH | Performance of the biomarker signatures will be assessed using ROC curve in participants with pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), isolated pre-capillary and post-capillary PH. | Day 1 |