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

October 25, 2018 updated by: Jan Grimminger, University of Giessen

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Nauheim, Germany
        • Kerckhoff-Klinik
    • Hesse
      • Giessen, Hesse, Germany, 35392
        • University Clinic Giessen and Marburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Iloprost
Single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change of PVR (∆PVR)
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
5, 10, 15, 30 minutes after the end of inhalation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Change of mPAP
Time Frame: at baseline and 5, 10, 15, 30 minutes after the end of inhalation
at baseline and 5, 10, 15, 30 minutes after the end of inhalation
Change of PAWP
Time Frame: at baseline and 5, 10, 15, 30 minutes after the end of inhalation
at baseline and 5, 10, 15, 30 minutes after the end of inhalation
Change of CI
Time Frame: at baseline and 5, 10, 15, 30 minutes after the end of inhalation
at baseline and 5, 10, 15, 30 minutes after the end of inhalation
Change of systemic blood pressure
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
5, 10, 15, 30 minutes after the end of inhalation
Change of oxygen saturation
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
5, 10, 15, 30 minutes after the end of inhalation
Change of right heart echocardiography
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
5, 10, 15, 30 minutes after the end of inhalation
Adverse events (AEs)
Time Frame: 5, 10, 15, 30 minutes after the end of inhalation
5, 10, 15, 30 minutes after the end of inhalation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Giessen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 24, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 7, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • V04_21112017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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