A Study for the Identification of Biomarker Signatures for Diagnosis of Pulmonary Hypertension (PH) in Participants at Low or Intermediate Probability of PH Undergoing Cardiac Magnetic Resonance Imaging

Study Overview
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Brief Summary
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The primary purpose of this study is to estimate the percentage of participants in the population considered clinically as not having pulmonary hypertension (PH) that are positive for PH biomarker (micro ribonucleic acid [RNA]); estimate the percentage of participants in the population considered clinically as not having PH that are positive for PH by cardiac magnetic resonance imaging (MRI) and compare results of the MRI to the biomarker results; to determine the performance of the biomarker signatures identified in the CIPHER (NAPUH0001) study in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), in a population considered clinically as not having PH.

Official Title
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A Prospective Multicenter Study for the Assessment of Biomarker Signatures for the Diagnosis of Pulmonary Hypertension (PH) in Patients at Low or Intermediate Probability of PH Undergoing Cardiac Magnetic Resonance Imaging (MRI) CIPHER-MRI

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Other: Blood Sample
* Diagnostic Test: Cardiac MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Referred for diagnostic work-up for pulmonary hypertension (PH) With low or intermediate (but not high) probability of PH by transthoracic echocardiography (TTE) according to European Society of Cardiology (ESC)/ European Respiratory Society (ERS) Guidelines if at the time of enrollment Right Heart Catheterization (RHC) is not deemed to be clinically indicated 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 sign an Informed consent (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study Must sign a separate approval in the ICF if he or she agrees to provide an optional (DNA) sample for research. Refusal to give consent for the optional (DNA) research sample does not exclude a participant from participation in the study Exclusion Criteria: Undergone RHC within 2 years Participants requiring renal dialysis Participants post-lung or heart transplant Severe left ventricular dysfunction: left ventricular ejection fraction less then (<) 35 percent Ongoing Contagious respiratory disease

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 Low or Intermediate Probability of PH<br>Participants who underwent a work-up for the suspicion of PH that includes transthoracic echocardiography (TTE) and who were considered to have a low or intermediate probability of PH according to TTE (local interpretation) will be enrolled. Blood samples will be taken and a cardiac magnetic resonance imaging (MRI) will be performed to evaluate the presence of Pulmonary Hypertension (PH). The TTEs that were performed by local standards will be collected and undergo central interpretation using European society of Cardiology / European respiratory society (ESC/ERS) guidelines to confirm the local interpretation. | Other: Blood Sample<br>* Blood samples will be taken and analyzed to evaluate the presence of PH.<br>Diagnostic Test: Cardiac MRI<br>* Cardiac MRI will be performed to evaluate the presence of PH.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in the Population Considered Clinically as not Having PH that are Positive for PH Biomarker | Percentage of (transthoracic echocardiography [TTE] low/intermediate probability) participants who are positive for the biomarker will be estimated. | Up to 90 Days | 
| Percentage of Participants Considered Clinically as not Having PH that are Positive for PH by Cardiac MRI | Percentage of participants considered clinically as not having PH that are positive for PH by cardiac magnetic resonance imaging (MRI) will be evaluated. | Up to 90 Days | 
| Performance of Biomarker Results | The performance of the biomarker in the diagnosis of PH will be evaluated using the MRI result. | Up to 90 Days | 
| Performance of the Biomarker Signatures Identified in the CIPHER Study in Terms of Sensitivity, specificity, positive predictive value (PPV) and Negative Predictive Value (NPV), in Participants not Having PH | Performance of the biomarker signatures identified in the CIPHER study in terms of sensitivity, specificity, PPV and NPV, in a population considered clinically as not having PH will be estimated. | Up to 90 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker Data Pooled with the Biomarker Data Collected from the CIPHER (NAPUH0001) Study | The biomarker data collected from participants with low/intermediate suspicion of PH in the CIPHER-MRI study will be pooled with the data collected from the high to intermediate suspicion of PH participants in the CIPHER (NAPUH0001) study to evaluate the performance of the biomarker signature(s) developed in CIPHER (NAPUH0001). | Up to 90 Days |