- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03365479
Acute Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension
Acute Hemodynamic Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension
Primary objective
• To evaluate the effect of rapid inhalation of 2.5μgiloprost using the Breelib nebulizer on pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension
Secondary objectives
- To evaluate the effect of rapid iloprost inhalation using the Breelib nebulizer on mean pulmonary arterial pressure (mPAP), cardiac output (CO), cardiac index (CI), systemic blood pressure, arterial oxygen saturation, heart rate, and pulmonary arterial wedge pressure (PAWP).
- To evaluate the safety and tolerability of the rapid iloprost inhalation using the Breelib nebulizer.
Study Overview
Status
Intervention / Treatment
Detailed Description
This study aims to investigate the acute hemodynamic and pharmacological effects of a single inhalation of Iloprost (2.5μg) during right heart catheterization (RHC) using the Breelib nebulizer. Patients with confirmed diagnosis of pulmonary arterial hypertension (PAH = WHO group 1), NYHA functional class III and with stable background pulmonary vasoactive treatment or treatment naïve PAH patients will be challenged with the iloprost inhalation dosage during RHC. As a proof-of concept design, the study will include consecutive PAH patients only challenged with a single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer during right heart catheterization (day 2).
The acute hemodynamic response will be followed over 30 minutes. Change of pulmonary hemodynamics, systemic blood pressure, right ventricular echocardiographic parameters and adverse events will be assessed at baseline and 5, 10, 15, 30 minutes after the end of inhalation.
Recently, the Breelib nebulizer has been evaluated within a multicenter, randomized, unblinded, study. This safety and feasibility study compared inhalation time, pharmacokinetics, and acute tolerability of inhaled iloprost delivered via Breelib versus the standard I-Neb nebulizer. The primary safety endpoints (AEs) were reported with a low frequency and were consistent with the known safety profile of iloprost. Median inhalation times were considerably shorter while maximum iloprost plasma concentration and systemic exposure were significantly higher, with Breelib versus I-Neb. Previously, it was shown that the acute hemodynamic response of iloprost inhalation via the previous used I-Neb nebulizer resulted in a relevant and significant reduction of PVR and increase in CI. Moreover, previous generation of nebulizers also resulted in a significant reduction of PVR and increase in CI 5-15min after iloprost inhalation.
Therefore, the aim of the current study is to determine the acute hemodynamic effects on the pulmonary and the systemic circulation as well as on the gas exchange of 2.5 μg iloprost delivered via the Breelib device. The investigators aim to characterize the hemodynamic profile of the inhalation with Breelib as the investigators speculate that the shortened inhalation time will result in an enhanced hemodynamic response with substantial reduction of pulmonary vascular resistance (PVR). Moreover, as a secondary outcome measurement the investigators aim to assess the response of mean pulmonary arterial pressure, cardiac index/cardiac output, systemic blood pressure, right ventricular echocardiographic parameters and oxygen saturation after inhalation of 2.5μg iloprost and analyze adverse events.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Bad Nauheim, Germany
- Kerckhoff-klinik
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Hesse
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Giessen, Hesse, Germany, 35392
- University Clinic Giessen and Marburg
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed diagnosis of pulmonary arterial hypertension, WHO group 1 diagnosed according to current guidelines
- New York Heart Association functional class III
- mPAP ≥ 25 mmHg, PAWP ≤ 15 mmHg
- Age ≥ 18 years; ≤ 85 years
- planned right heart catheterization based on clinical grounds
- Stable specific PAH medications other than prostanoids
- Signed informed consent
Exclusion Criteria:
- other etiologic groups of pulmonary hypertension (WHO group 2, 3, 4, 5)
- Unstable or severe coronary artery disease (history of cardiac surgery, history of coronary intervention 2 years prior to inclusion), uncontrolled arterial hypertension, severe left ventricular hypertrophy, severe congenital or acquired valvular or myocardial disease, systolic blood pressure < 90 mmHg, heart rate of <55 or >105 beats·min-1 before inhalation
- Progressive left heart failure History of severe ventricular arrhythmias
- Pulmonary veno-occlusive disease
- Transitory ischemic attack (TIA) or stroke ≤ 3months
- Severe hepatic impairment (> CHILD B)
- Severe, terminal renal impairment
- Use of intravenous, subcutaneous or oral prostacyclin/IP receptor agonists
- Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Study cohort
The study comprises a 1-day Screening period, followed by a right heart catheterization with a single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer
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Single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change of PVR (∆PVR)
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
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5, 10, 15, 30 minutes after the end of inhalation
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change of mPAP
Time Frame: at baseline and 5, 10, 15, 30 minutes after the end of inhalation
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at baseline and 5, 10, 15, 30 minutes after the end of inhalation
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Change of PAWP
Time Frame: at baseline and 5, 10, 15, 30 minutes after the end of inhalation
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at baseline and 5, 10, 15, 30 minutes after the end of inhalation
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Change of CI
Time Frame: at baseline and 5, 10, 15, 30 minutes after the end of inhalation
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at baseline and 5, 10, 15, 30 minutes after the end of inhalation
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Change of systemic blood pressure
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
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5, 10, 15, 30 minutes after the end of inhalation
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Change of oxygen saturation
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
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5, 10, 15, 30 minutes after the end of inhalation
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Change of right heart echocardiography
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
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5, 10, 15, 30 minutes after the end of inhalation
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Adverse events (AEs)
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
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5, 10, 15, 30 minutes after the end of inhalation
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- V04_21112017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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