## Protocol Section
### Identification Module
**NCT ID:** NCT03365479

**Brief Title:** Acute Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension

**Official Title:** Acute Hemodynamic Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension

#### Organization Study ID Info
**ID:** V04_21112017
#### Organization
**Class:** OTHER
**Full Name:** University of Giessen
### Status Module
#### Completion Date
**Date:** 2018-10-24

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-10-26

**Type:** ACTUAL

**Last Update Submit Date:** 2018-10-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2018-08-01

**Type:** ACTUAL

#### Start Date
**Date:** 2017-05-01

**Type:** ACTUAL

**Status Verified Date:** 2018-10

#### Study First Post Date
**Date:** 2017-12-07
**Type:** ACTUAL
**Study First Submit Date:** 2017-11-27
**Study First Submit QC Date:** 2017-12-01
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Giessen

#### Responsible Party

**Investigator Affiliation:** University of Giessen

**Investigator Full Name:** Jan Grimminger

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

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Pulmonary Hypertension

- Pulmonary Arterial Hypertension

**Keywords:**

- pulmonary hypertension

- iloprost

- inhaled

- breelib

- nebulizer

- pulmonary arterial hypertension

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 30

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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

**Intervention Names:**

- Drug: Iloprost

**Label:** Study cohort

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Study cohort

**Description:** Single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer

**Name:** Iloprost

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Change of PVR (∆PVR)

**Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation

#### Secondary Outcomes

**Measure:** Change of mPAP

**Time Frame:** at baseline and 5, 10, 15, 30 minutes after the end of inhalation

**Measure:** Change of PAWP

**Time Frame:** at baseline and 5, 10, 15, 30 minutes after the end of inhalation

**Measure:** Change of CI

**Time Frame:** at baseline and 5, 10, 15, 30 minutes after the end of inhalation

**Measure:** Change of systemic blood pressure

**Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation

**Measure:** Change of oxygen saturation

**Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation

**Measure:** Change of right heart echocardiography

**Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation

**Measure:** Adverse events (AEs)

**Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation

### Eligibility Module

**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 Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Giessen

**Country:** Germany

**Facility:** University Clinic Giessen and Marburg

**State:** Hesse

**Zip:** 35392

**Location 2:**

**City:** Bad Nauheim

**Country:** Germany

**Facility:** Kerckhoff-Klinik

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: Hypertension

- ID: M27137

- Name: Respiratory Aspiration

- Relevance: LOW

- As Found: Unknown

- ID: M10027

- Name: Hypertension, Pulmonary

- Relevance: HIGH

- As Found: Pulmonary Hypertension

- ID: M2261

- Name: Pulmonary Arterial Hypertension

- Relevance: HIGH

- As Found: Pulmonary Arterial Hypertension

- ID: M30541

- Name: Familial Primary Pulmonary Hypertension

- Relevance: HIGH

- As Found: Pulmonary Arterial Hypertension

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T4807

- Name: Pulmonary Arterial Hypertension

- Relevance: HIGH

- As Found: Pulmonary Arterial Hypertension

### Condition Browse Module - Meshes

- ID: D000006976

- Term: Hypertension, Pulmonary

- ID: D000081029

- Term: Pulmonary Arterial Hypertension

- ID: D000065627

- Term: Familial Primary Pulmonary Hypertension

- ID: D000006973

- Term: Hypertension

### Intervention Browse Module - Ancestors

- ID: D000010975

- Term: Platelet Aggregation Inhibitors

- ID: D000014665

- Term: Vasodilator Agents

### Intervention Browse Module - Browse Branches

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: PlAggInh

- Name: Platelet Aggregation Inhibitors

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M18735

- Name: Iloprost

- Relevance: HIGH

- As Found: Cyst

- ID: M13865

- Name: Platelet Aggregation Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000016285

- Term: Iloprost

### Misc Info Module

- Version Holder: 2024-05-24
