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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00810693
Registration number
NCT00810693
Ethics application status
Date submitted
17/12/2008
Date registered
18/12/2008
Date last updated
22/11/2023
Titles & IDs
Public title
A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH)
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Scientific title
Randomized, Double-blind, Placebo-controlled, Multi-centre, Multi-national Study to Evaluate the Efficacy and Safety of Oral BAY63-2521 (1 mg, 1.5 mg, 2 mg, or 2.5 mg Tid) in Patients With Symptomatic Pulmonary Arterial Hypertension (PAH)
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Secondary ID [1]
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2008-003482-68
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Secondary ID [2]
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12934
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Universal Trial Number (UTN)
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Trial acronym
PATENT-1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Pulmonary Hypertension
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Condition category
Condition code
Respiratory
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Other respiratory disorders / diseases
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Cardiovascular
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Hypertension
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Placebo
Experimental: Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT - Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks
Experimental: Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT - Participants received Riociguat orally as a film-coated tablet up to 1.5mg three times daily (tid) (titration between 1.0 mg and 1.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks
Placebo comparator: Placebo - Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
BAY63-2521: 1mg tid - 2.5mg tid orally for 12 weeks
Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
BAY63-2521: 1.5mg tid orally for 12 weeks
Treatment: Drugs: Placebo
Matching Placebo tid orally for 12 weeks
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12
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Assessment method [1]
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6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
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Timepoint [1]
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Baseline and week 12
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Secondary outcome [1]
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Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12
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Assessment method [1]
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The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80\*(PAPmean - PCWP)/CO
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Timepoint [1]
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Baseline and week 12
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Secondary outcome [2]
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N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12
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Assessment method [2]
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N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.
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Timepoint [2]
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Baseline and week 12
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Secondary outcome [3]
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World Health Organization (WHO) Functional Class - Change From Baseline to Week 12
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Assessment method [3]
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The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (participants with PH but without resulting limitation of physical activity) to class IV (participants with PH with inability to carry out any physical activity without symptoms. These participants manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH.
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Timepoint [3]
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Baseline and week 12
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Secondary outcome [4]
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Percentage of Participants With Clinical Worsening
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Assessment method [4]
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The combined endpoint "time to clinical worsening", made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; atrial septostomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH .
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Timepoint [4]
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At week 12
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Secondary outcome [5]
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Borg CR 10 Scale - Change From Baseline to Week 12
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Assessment method [5]
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The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal").
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Timepoint [5]
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Baseline and week 12
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Secondary outcome [6]
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EQ-5D Utility Score - Change From Baseline to Week 12
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Assessment method [6]
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EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).
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Timepoint [6]
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Baseline and week 12
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Secondary outcome [7]
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Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12
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Assessment method [7]
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The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst).
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Timepoint [7]
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Baseline and week 12
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Eligibility
Key inclusion criteria
* Male and female patients with symptomatic PAH (Idiopathic, Familial, Associated PAH due to connective tissue disease, congenital heart disease, portal hypertension with liver cirrhosis, or due to anorexigen or amphetamine use)
* Treatment naive patients and patients pre-treated with an Endothelin Antagonist or a Prostacyclinanalogue (except I.V.).
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Minimum age
18
Years
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Maximum age
80
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* All types of pulmonary hypertension except subtypes of Venice Group I specified in the inclusion criteria, severe COPD (chronic obstructive pulmonary disease), uncontrolled arterial hypertension, left heart failure.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
17/12/2008
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
14/05/2012
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Sample size
Target
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Accrual to date
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Final
445
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
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Recruitment hospital [1]
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- Darlinghurst
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Recruitment hospital [2]
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- New Lambton Heights
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- Auchenflower
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- Herston
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Royal Hobart Hospital - Hobart
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Recruitment hospital [6]
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- Prahran
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2010 - Darlinghurst
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2305 - New Lambton Heights
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4066 - Auchenflower
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4029 - Herston
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7000 - Hobart
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Recruitment postcode(s) [6]
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3181 - Prahran
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Recruitment outside Australia
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United Kingdom
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Bayer
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521 given orally for 12 weeks, in patients with symptomatic Pulmonary Arterial Hypertension (PAH).
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Trial website
https://clinicaltrials.gov/study/NCT00810693
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Trial related presentations / publications
Archer SL. Riociguat for pulmonary hypertension--a glass half full. N Engl J Med. 2013 Jul 25;369(4):386-8. doi: 10.1056/NEJMe1306684. No abstract available. Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ; PATENT-1 Study Group. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013 Jul 25;369(4):330-40. doi: 10.1056/NEJMoa1209655. Rosenkranz S, Ghofrani HA, Beghetti M, Ivy D, Frey R, Fritsch A, Weimann G, Saleh S, Apitz C. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart. 2015 Nov;101(22):1792-9. doi: 10.1136/heartjnl-2015-307832. Epub 2015 Jul 1. Wang C, Jing ZC, Huang YG, Zhou DX, Liu ZH, Meier C, Nikkho S, Curram J, Zhang P, He JG. Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison. Heart Asia. 2016 May 17;8(1):74-82. doi: 10.1136/heartasia-2015-010712. eCollection 2016. Ghofrani HA, Humbert M, Langleben D, Schermuly R, Stasch JP, Wilkins MR, Klinger JR. Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension. Chest. 2017 Feb;151(2):468-480. doi: 10.1016/j.chest.2016.05.024. Epub 2016 Jun 2. Benza RL, Boucly A, Farber HW, Frost AE, Ghofrani HA, Hoeper MM, Lambelet M, Rahner C, Bansilal S, Nikkho S, Meier C, Sitbon O. Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study. J Heart Lung Transplant. 2022 Mar;41(3):411-420. doi: 10.1016/j.healun.2021.10.013. Epub 2021 Oct 28. Benza RL, Farber HW, Frost AE, Ghofrani HA, Corris PA, Lambelet M, Nikkho S, Meier C, Hoeper MM. Application of the REVEAL risk score calculator 2.0 in the CHEST study. Respir Med. 2022 Apr-May;195:106783. doi: 10.1016/j.rmed.2022.106783. Epub 2022 Mar 1. Benza RL, Ghofrani HA, Grunig E, Hoeper MM, Jansa P, Jing ZC, Kim NH, Langleben D, Simonneau G, Wang C, Busse D, Meier C, Ghio S. Effect of riociguat on right ventricular function in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant. 2021 Oct;40(10):1172-1180. doi: 10.1016/j.healun.2021.06.020. Epub 2021 Jul 10. Humbert M, Coghlan JG, Ghofrani HA, Grimminger F, He JG, Riemekasten G, Vizza CD, Boeckenhoff A, Meier C, de Oliveira Pena J, Denton CP. Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann Rheum Dis. 2017 Feb;76(2):422-426. doi: 10.1136/annrheumdis-2015-209087. Epub 2016 Jul 25. Saleh S, Becker C, Frey R, Muck W. Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulm Circ. 2016 Mar;6(Suppl 1):S86-96. doi: 10.1086/685404.
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Results publications and other study-related documents
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Journal
Archer SL. Riociguat for pulmonary hypertension--a...
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Ghofrani HA, Galie N, Grimminger F, Grunig E, Humb...
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Rosenkranz S, Ghofrani HA, Beghetti M, Ivy D, Frey...
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Wang C, Jing ZC, Huang YG, Zhou DX, Liu ZH, Meier ...
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Ghofrani HA, Humbert M, Langleben D, Schermuly R, ...
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Benza RL, Boucly A, Farber HW, Frost AE, Ghofrani ...
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Benza RL, Farber HW, Frost AE, Ghofrani HA, Corris...
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Results are available at
https://clinicaltrials.gov/study/NCT00810693
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