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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT04193046

Collaborator

(none)

908

Enrollment

Locations

Arm

26.1

Actual Duration (Months)

18.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Pulmonary	Other: Blood Sample	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

908 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Dec 16, 2019

Actual Primary Completion Date :

Dec 20, 2021

Actual Study Completion Date :

Feb 18, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Expression Levels of miRNAs Biomarkers [Day 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 miRNA [Day 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 PH [Day 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 Value [Day 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

Area Under ROC Curve in Participants with PH who are Receiving Therapies Versus not Receiving drug Therapy [Day 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 PH [Day 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (%)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	University Of Colorado Cardiac And Vascular Center	Aurora	Colorado	United States	80045-2548
3	Ascension St. Vincent's Lung Institute	Jacksonville	Florida	United States	32204
4	Mayo Clinic	Jacksonville	Florida	United States	32224
5	University Of Iowa - Hospitals & Clinics	Iowa City	Iowa	United States	52242
6	Norton Pulmonary Specialists	Louisville	Kentucky	United States	40202
7	LSU Health Sciences Center New Orleans	New Orleans	Louisiana	United States	70112
8	Tufts Medical Center	Boston	Massachusetts	United States	02111-1552
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-5990
11	Pulmonary Health Physicians, PC	Liverpool	New York	United States	13088
12	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
13	University of Cincinnati	Cincinnati	Ohio	United States	45267
14	UT Southwestern Medical Center	Dallas	Texas	United States	75390-8550
15	The Houston Methodist Research Institute	Houston	Texas	United States	77030
16	Pulmonary Associates Of Richmond	Richmond	Virginia	United States	23230
17	ULB Erasme Ziekenhuis	Bruxelles		Belgium	1070
18	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
19	CHU de Brest - Hôpital de la Cavale Blanche	Brest		France	29200
20	Hopital de Bicetre	Le Kremlin-Bicêtre		France	94270
21	Hôpital Cardiologique - Chru Lille	Lille Cedex		France	59037
22	CHU de Montpellier - Arnaud de Villeneuve	MONTPELLIER Cedex 5		France	34295
23	Hopital Larrey CHU de Toulouse	Toulouse		France	31059
24	Universitatsklinikum Bonn	Bonn		Germany	53105
25	Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie	Dresden		Germany	01307
26	Universitaetsklinikum Giessen	Giessen		Germany	35392
27	Thoraxklinik Heidelberg	Heidelberg		Germany	69126
28	Lungenfachklinik Immenhausen	Immenhaus		Germany	34376
29	Universitätsklinikum Jena Klinik für Innere Medizin I	Jena		Germany	07747
30	Universitätsklinikum Schleswig-Holstein	Luebeck		Germany	23538
31	VUMC Amsterdam	Amsterdam		Netherlands	1007 MB
32	Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego	Lublin		Poland	20-718
33	Europejskie Centrum Zdrowia Otwock Sp. z o.o	Otwock		Poland	05-400
34	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM	Szczecin		Poland	70-111
35	Hosp. Univ. Vall D Hebron	Barcelona		Spain	8035
36	Hosp. Clinic I Provincial de Barcelona	Barcelona		Spain	8036
37	Hosp. Univ. 12 de Octubre	Madrid		Spain	28051
38	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37008
39	Hosp. Univ. Marques de Valdecilla	Santander		Spain	39008
40	Hosp. Virgen de La Salud	Toledo		Spain	45004
41	CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'	Cherkasy		Ukraine	18009
42	CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'	Dnipro		Ukraine	49070
43	SI 'National Scientific Center Institute of Cardiology of M.D. Strazhesko' of NAMS of Ukraine	Kyiv		Ukraine	02000
44	SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'	Kyiv		Ukraine	03038
45	Royal United Hospital	Bath		United Kingdom	BA1 3NG
46	National Waiting Times Centre Board Golden Jubilee National Hospital	Glasgow		United Kingdom	G81 4DY
47	Royal Free Hospital	London		United Kingdom	NW3 2QG
48	Hammersmith Hospital	London		United Kingdom	W12 0HS
49	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2RX

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen Research & Development, LLC

ClinicalTrials.gov Identifier:

NCT04193046

Other Study ID Numbers:

CR108723
NAPUH0001

First Posted:

Dec 10, 2019

Last Update Posted:

Apr 27, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hypertension, Pulmonary

Hypertension

Study Results

No Results Posted as of Apr 27, 2022