Effect of BMPR-2 Gene Mutations on Hemodynamic Response by Iloprost Inhalation in Pulmonary Arterial Hypertension

NCT01054105 | Completed

• 2 other identifiers: WJC-IIT-1001GIRBA 2278
• Study Type: observational
• Target: 73
• Locations: 1 country
• Sites: 6

Brief Summary

In the present study, the investigators want to investigate the prevalence of BMPR-2 gene mutations in the Korean PAH patients (Step-I) and to test that the PAH patients treated with iloprost inhalation solution (Ventavis®) would show hemodynamic response, especially assessed by exercise echocardiography (Step-II).

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary hypertension; genes; mutation; drug therapy

Outcome Measures

Primary Outcomes (1)

• Cardiopulmonary exercise test parameters

  after 3 months active follow-up

Secondary Outcomes (5)

• Major cardiovascular Events (cardiovascular mortality, all cause mortality, hospitalization)

  After 2 years follow-up

• Six-minutes walking test

  After 3 months active follow-up

• WHO/NYHA class

  After 3 months active follow-up

• Echo parameters

  After 3 months active follow-up

• NT-proBNP

  After 3 months active follow-up

Study Arms (2)

Step I: BMPR-2 gene analysis

BMPR-2 gene analysis on 100 IPAH or heritable PAH Patients

Drug: Iloprost

Step-II: Iloprost and Exercise Echo

Illoprost inhalation for 3 months \& Check-up before and after treatment; WHO functional classification Assessment of exercise capacity (6M walk test) Cardiopulmonary exercise echocardiography NT-proBNP

Drug: Iloprost

Interventions

Iloprost DRUG

Iloprost inhalation, 2.5 - 5mcg, 6 times per day

Also known as: Allowable patients from Step-I, Step-II: Illoprost and Exercise Echo

Step I: BMPR-2 gene analysis; Step-II: Iloprost and Exercise Echo

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Previously diagnosed PAH

You may qualify if:

• The patients aged from 20 to 80 years
• Newly diagnosed WHO category I PAH patients: Patients who meet the following criteria within 3 months obtained by right heart catheterization (mean PAP of more than 25 mm Hg at rest and mean pulmonary arterial wedge pressure (PCWP) or left ventricular end-diastolic pressure of 15 mm Hg or less) or echocardiography (peak PAP of more than 40mmHg and mean PAP more than 30mmHg).
• Previously diagnosed PAH patients who refractory to conventional treatment except iloprost inhalation solution (Ventavis): Patients meet the echo criteria (peak PAP of more than 40mmHg and mean PAP more than 30mmHg) who have been treated with PAH medications except iloprost inhalation solution (Ventavis) after diagnosed as WHO Group 1 PAH based on prior RHC data (above criteria) but refractory to them.
• The patients who are able to undergo low intensity exercise test (low dose bicycle or walking)

You may not qualify if:

• The patients with other left heart disease (category II in WHO classification of pulmonary hypertension); ex. Congestive HF, cardiomyopathy, significant valvular heart disease, significant arrhythmia, suspicious elevated PCWP.
• The patients with category III,IV and V in WHO classification of pulmonary hypertension:
• Pulmonary hypertension with lung disease and/or hypoxemia
• Chronic obstructive pulmonary disease
• Interstitial lung disease
• Sleep disorder breathing
• Alveolar hyperventilation disorders
• Chronic exposure to high altitude
• Developmental abnormalities
• Pulmonary hypertension due to chronic thrombotic and/or embolic disease
• Thromboembolic obstruction of the proximal pulmonary arteries
• Thromboembolic obstruction of the distal pulmonary arteries
• Non-thrombotic pulmonary embolism (e.g. tumor or parasitic)
• Miscellaneous disorders affecting the pulmonary vasculature
• Patients with contraindication to Ventavis;(Hypersensitive to Ventavis, High risk of bleeding, which can be increased by use of Ventavis (e.g. active peptic ulcer, trauma, intracranial hemorrhage)

Sponsors & Collaborators

• Gachon University Gil Medical Center: lead
• Seoul National University Hospital: collaborator
• Seoul National University Bundang Hospital: collaborator
• The Catholic University of Korea: collaborator
• Bayer: collaborator

Study Sites (6)

Soonchunhyang University Bucheon Hospital

Bucheon-si, South Korea

Location

Gachon University Gil Hospital

Incheon, 405-760, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Catholic University Seoul Saint Mary's Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Sungkyunkwan University Seoul Samsung Hospital

Seoul, South Korea

Location

Related Publications (1)

• Jang AY, Kim BG, Kwon S, Seo J, Kim HK, Chang HJ, Chang SA, Cho GY, Rhee SJ, Jung HO, Kim KH, Seo HS, Kim KH, Shin J, Lee JS, Kim M, Lee YJ, Chung WJ. Prevalence and clinical features of bone morphogenetic protein receptor type 2 mutation in Korean idiopathic pulmonary arterial hypertension patients: The PILGRIM explorative cohort. PLoS One. 2020 Sep 23;15(9):e0238698. doi: 10.1371/journal.pone.0238698. eCollection 2020.

  PMID: 32966279 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

BMPR-2 genes

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

Iloprost

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Wook-Jin Chung, MD,PhD

  Gachon University Gil Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 21, 2010
• First Posted: January 22, 2010
• Study Start: October 1, 2010
• Primary Completion: December 25, 2018
• Study Completion: December 25, 2018
• Last Updated: December 27, 2018

Record last verified: 2018-12

Locations

KR (6)