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

Early Phase 1
Completed
Conditions
Hypertension, Pulmonary
Interventions
Other: Blood Sample
Registration Number
NCT04193046
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
908
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
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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 (%)
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Participants with PH and non-PHBlood SampleBlood 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.
Primary Outcome Measures
NameTimeMethod
Expression Levels of miRNAs BiomarkersDay 1

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).

Biomarker signatures for miRNADay 1

Blood will be collected for miRNA to identify a biomarker signature(s) for detection of participants at high risk of PH.

Biomarker Signature Performance in Identifying Participants with PHDay 1

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.

Comparison of Performance of Biomarker Signatures and Transthoracic Echocardiogram (TTE) Based on Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive ValueDay 1

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.

Secondary Outcome Measures
NameTimeMethod
Area Under ROC Curve in Participants with PH who are Receiving Therapies Versus not Receiving drug TherapyDay 1

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.

Area Under ROC Curve in Participants with PAH, CTEPH, Isolated pre-Capillary and post-Capillary PHDay 1

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.

Trial Locations

Locations (48)

Europejskie Centrum Zdrowia Otwock Sp. z o.o

🇵🇱

Otwock, Poland

Universitatsklinikum Bonn

🇩🇪

Bonn, Germany

Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego

🇵🇱

Lublin, Poland

Ascension St. Vincent's Lung Institute

🇺🇸

Jacksonville, Florida, United States

Norton Pulmonary Specialists

🇺🇸

Louisville, Kentucky, United States

VUMC Amsterdam

🇳🇱

Amsterdam, Netherlands

Hammersmith Hospital

🇬🇧

London, United Kingdom

Hosp. Univ. Marques de Valdecilla

🇪🇸

Santander, Spain

Hosp. Univ. Vall D Hebron

🇪🇸

Barcelona, Spain

Hosp. Univ. 12 de Octubre

🇪🇸

Madrid, Spain

SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'

🇺🇦

Kyiv, Ukraine

Hopital de Bicetre

🇫🇷

Le Kremlin-Bicêtre, France

Universitaetsklinikum Giessen

🇩🇪

Giessen, Germany

Universitätsklinikum Schleswig-Holstein

🇩🇪

Luebeck, Germany

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

🇬🇧

Sheffield, United Kingdom

Thoraxklinik Heidelberg

🇩🇪

Heidelberg, Germany

Hosp. Clinico Univ. de Salamanca

🇪🇸

Salamanca, Spain

Royal Free Hospital

🇬🇧

London, United Kingdom

CHU de Brest - Hôpital de la Cavale Blanche

🇫🇷

Brest, France

Hosp. Virgen de La Salud

🇪🇸

Toledo, Spain

Hosp. Clinic I Provincial de Barcelona

🇪🇸

Barcelona, Spain

Lungenfachklinik Immenhausen

🇩🇪

Immenhaus, Germany

Royal United Hospital

🇬🇧

Bath, United Kingdom

National Waiting Times Centre Board Golden Jubilee National Hospital

🇬🇧

Glasgow, United Kingdom

Universitätsklinikum Jena Klinik für Innere Medizin I

🇩🇪

Jena, Germany

University Of Colorado Cardiac And Vascular Center

🇺🇸

Aurora, Colorado, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

University Of Iowa - Hospitals & Clinics

🇺🇸

Iowa City, Iowa, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Pulmonary Health Physicians, PC

🇺🇸

Liverpool, New York, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Hopital Larrey CHU de Toulouse

🇫🇷

Toulouse, France

Pulmonary Associates Of Richmond

🇺🇸

Richmond, Virginia, United States

Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie

🇩🇪

Dresden, Germany

Hôpital Cardiologique - Chru Lille

🇫🇷

Lille Cedex, France

CHU de Montpellier - Arnaud de Villeneuve

🇫🇷

MONTPELLIER Cedex 5, France

Samodzielny Publiczny Szpital Kliniczny nr 2 PUM

🇵🇱

Szczecin, Poland

CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'

🇺🇦

Dnipro, Ukraine

SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine

🇺🇦

Kyiv, Ukraine

ULB Erasme Ziekenhuis

🇧🇪

Bruxelles, Belgium

UZ Leuven Gasthuisberg

🇧🇪

Leuven, Belgium

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'

🇺🇦

Cherkasy, Ukraine

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

LSU Health Sciences Center New Orleans

🇺🇸

New Orleans, Louisiana, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

The Houston Methodist Research Institute

🇺🇸

Houston, Texas, United States

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