Acute Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension

NCT ID: NCT03365479

Last Updated: 2018-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2018-10-24

Brief Summary

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.

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.

Conditions

Pulmonary Hypertension; Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Iloprost

Intervention Type: DRUG

Single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer

Interventions

Iloprost

Single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Giessen

OTHER

Sponsor Role: lead

Responsible Party

Jan Grimminger

Study Chair: Ghofrani H. Ardeschir, Prof. Dr. University of Giessen

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Clinic Giessen and Marburg

Giessen, Hesse, Germany

Kerckhoff-Klinik

Bad Nauheim, , Germany

Countries

Germany

Other Identifiers

V04_21112017

Identifier Type: -

Identifier Source: org_study_id