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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Other: Blood Sample; Diagnostic test: Cardiac MRI

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn
  • Giessen, Germany, 35392
    • Universitaetsklinikum Giessen
  • Luebeck, Germany, 23538
    • Universitätsklinikum Schleswig Holstein
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Royal United Hospital
  • Glasgow, United Kingdom, G81 4DY
    • National Waiting Times Centre Board Golden Jubilee National Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Sheffield, United Kingdom, S10 2RX
    • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Participants with Low or Intermediate Probability of PH; 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; Blood samples will be taken and analyzed to evaluate the presence of PH.; Diagnostic test: Cardiac MRI; Cardiac MRI will be performed to evaluate the presence of PH.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Actelion Clinical Trial, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2020
• Primary Completion (Actual): May 13, 2022
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: CR108827; NAPUH0003 (Other Identifier: Actelion)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No