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

Hypertension, Pulmonary Clinical Trial

— CIPHER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04193046
• Other study ID #: CR108723
• Secondary ID: NAPUH0001
• Status: Completed
• Phase: Early Phase 1
• Start date: December 16, 2019
• Est. completion date: February 18, 2022

Study information

• Verified date: April 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 908
• Est. completion date: February 18, 2022
• Est. primary completion date: December 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (%)

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary

Intervention

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.

Locations

Country	Name	City	State
Belgium	ULB Erasme Ziekenhuis	Bruxelles
Belgium	UZ Leuven Gasthuisberg	Leuven
France	CHU de Brest - Hôpital de la Cavale Blanche	Brest
France	Hopital de Bicetre	Le Kremlin-Bicêtre
France	Hôpital Cardiologique - Chru Lille	Lille Cedex
France	CHU de Montpellier - Arnaud de Villeneuve	MONTPELLIER Cedex 5
France	Hopital Larrey CHU de Toulouse	Toulouse
Germany	Universitatsklinikum Bonn	Bonn
Germany	Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie	Dresden
Germany	Universitaetsklinikum Giessen	Giessen
Germany	Thoraxklinik Heidelberg	Heidelberg
Germany	Lungenfachklinik Immenhausen	Immenhaus
Germany	Universitätsklinikum Jena Klinik für Innere Medizin I	Jena
Germany	Universitätsklinikum Schleswig-Holstein	Luebeck
Netherlands	VUMC Amsterdam	Amsterdam
Poland	Wojewódzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego	Lublin
Poland	Europejskie Centrum Zdrowia Otwock Sp. z o.o	Otwock
Poland	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM	Szczecin
Spain	Hosp. Clinic I Provincial de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Virgen de La Salud	Toledo
Ukraine	CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'	Cherkasy
Ukraine	CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'	Dnipro
Ukraine	SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'	Kyiv
Ukraine	SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine	Kyiv
United Kingdom	Royal United Hospital	Bath
United Kingdom	National Waiting Times Centre Board Golden Jubilee National Hospital	Glasgow
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital	Sheffield
United States	University Of Colorado Cardiac And Vascular Center	Aurora	Colorado
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Cincinnati	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	The Houston Methodist Research Institute	Houston	Texas
United States	University Of Iowa - Hospitals & Clinics	Iowa City	Iowa
United States	Ascension St. Vincent's Lung Institute	Jacksonville	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	Pulmonary Health Physicians, PC	Liverpool	New York
United States	University of Southern California	Los Angeles	California
United States	Norton Pulmonary Specialists	Louisville	Kentucky
United States	LSU Health Sciences Center New Orleans	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Pulmonary Associates Of Richmond	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Netherlands,  Poland,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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