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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Other: Blood Sample

• Study Type: Interventional
• Enrollment (Actual): 908
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • ULB Erasme Ziekenhuis
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• France
  • Brest, France, 29200
    • CHU de Brest - Hôpital de la Cavale Blanche
  • Le Kremlin-Bicêtre, France, 94270
    • Hopital de Bicetre
  • Lille Cedex, France, 59037
    • Hôpital Cardiologique - Chru Lille
  • MONTPELLIER Cedex 5, France, 34295
    • CHU de Montpellier - Arnaud de Villeneuve
  • Toulouse, France, 31059
    • Hopital Larrey CHU de Toulouse
• Germany
  • Bonn, Germany, 53105
    • Universitatsklinikum Bonn
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
  • Giessen, Germany, 35392
    • Universitaetsklinikum Giessen
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg
  • Immenhaus, Germany, 34376
    • Lungenfachklinik Immenhausen
  • Jena, Germany, 07747
    • Universitätsklinikum Jena Klinik für Innere Medizin I
  • Luebeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein
• Netherlands
  • Amsterdam, Netherlands, 1007 MB
    • VUMC Amsterdam
• Poland
  • Lublin, Poland, 20-718
    • Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego
  • Otwock, Poland, 05-400
    • Europejskie Centrum Zdrowia Otwock Sp. z o.o
  • Szczecin, Poland, 70-111
    • Samodzielny Publiczny Szpital Kliniczny nr 2 PUM
• Spain
  • Barcelona, Spain, 8035
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 8036
    • Hosp. Clinic I Provincial de Barcelona
  • Madrid, Spain, 28051
    • Hosp. Univ. 12 de Octubre
  • Salamanca, Spain, 37008
    • Hosp. Clinico Univ. de Salamanca
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Toledo, Spain, 45004
    • Hosp. Virgen de La Salud
• Ukraine
  • Cherkasy, Ukraine, 18009
    • CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'
  • Dnipro, Ukraine, 49070
    • CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
  • Kyiv, Ukraine, 02000
    • SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
  • Kyiv, Ukraine, 03038
    • SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'
• 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
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Aurora, Colorado, United States, 80045-2548
      • University Of Colorado Cardiac And Vascular Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jacksonville, Florida, United States, 32204
      • Ascension St. Vincent's Lung Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University Of Iowa - Hospitals & Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02111-1552
      • Tufts Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5990
      • University of Nebraska Medical Center
  • New York
    • Liverpool, New York, United States, 13088
      • Pulmonary Health Physicians, PC
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Texas
    • Dallas, Texas, United States, 75390-8550
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The Houston Methodist Research Institute
  • Virginia
    • Richmond, Virginia, United States, 23230
      • Pulmonary Associates of Richmond

Participation Criteria

Eligibility Criteria

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

Description

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 (%)

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 PH and non-PH; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2019
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): February 18, 2022

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: CR108723; NAPUH0001 (Other Identifier: Janssen Research & Development, LLC)

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