Effects of Roflumilast on Pulmonary Vascular Resistance in Patients with Chronic Obstructive Pulmonary Disease and Sleep Apnea (the so called Overlap Syndrome) with and without Non-invasive Ventilation. A Pilot Study.

Effects of Roflumilast on pulmonary vascular resistance in patients with COPD and sleep apnea (Overlap Syndrome) with and without non-invasive ventilation. A Pilot Study. - Effects of Roflumilast in Overlap Syndrome

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-003037-41-AT

Enrollment

Unknown

Registered

2012-08-08

Start date

2012-09-21

Completion date

Unknown

Last updated

2016-10-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

This study is about pulmonary hypertension due to lung diseases. The lung disease in this study will be the overlap syndrome which is defined as chronic obstructive pulmonary disease concomitant with sleep apnea. MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 14.1 Level: LLT Classification code 10040976 Term: Sleep apnea syndrome System Organ Class: 10038738 - Respiratory, th

Interventions

Trade Name: Daxas Pharmaceutical Form: Film-coated tablet INN or Proposed INN: ROFLUMILAST CAS Number: 162401-32-3 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 5

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: This study is aimed to show the effect of roflumilast on pulmonary vascular resistance in patients suffering from both sleep apnea and COPD, the so called overlap syndrome. Therefore inclusion criteria are based on gold standards for each disease separately. Adult patients with an age of >18 years fulfilling both, COPD and sleep apnea criteria, will be invited to participate in this study. COPD Regarding clinical experience and experimental data, pulmonary hypertension can be observed in patients with overlap syndrome even with only mild to moderate COPD. Hence, according to the GOLD criteria, we decided to include patients with COPD corresponding to a forced expiratory volume in 1 second (FEV1) 15 events per hour (moderate 15-30/h, severe >30/h) diagnosed by overnight polysomnography will be included in this study. Pulmonary Hemodynamics As the goal of this study is to investigate the effects of roflumilast on an abnormal pulmonary hemodynamical state, only those patients will be included who present with a PVR>150 dyn×s×cm-5 and a mPAP > 20mmHg at the baseline right heart catheterization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10

Exclusion criteria

Exclusion criteria: Underweight is very rare in patients suffering from sleep apnea as significant weight loss is important goal in these patients. Therefore weight loss which is a common side effect of roflumilast may be advantageous in the majority of patients with sleep apnea syndrome. Patients with a body mass index less than 20kg/m² will not be included in this study. Roflumilast is metabolized in the liver through cytochrome-P450 isoenzymes. Hence, roflumilast is contraindicated in patients with with moderate to severe liver failure. Patients with Child-Pugh class B to C will also be excluded from this study. Furthermore, patients working as professional drivers and patients with daytime hypercapnia ( pCO2 >55mmHg) will be excluded from this study. Further exclusion criteria: pregnancy, pulmonary hypertension due to other reasons, active clinical depression, therapy with roflumilast or NIV in history, immunosupression, treatment with combined CYP3A4/CYP1A2 inhibitors.

Design outcomes

Primary

Measure	Time frame
Main Objective: Our aim is to investigate if there is a measurable effect of roflumilast in patients suffering from overlap syndrome and pulmonary hypertension, who receive a sequential combination therapy of roflumilast as a potent PDE4 inhibitor and nocturnal non-invasive ventilation as add-on therapy. This pilot study could provide a rationale data for further studies addressing the role of PDE4 inhibitors and other novel anti-inflammatory drugs as a new potential treatment option for pulmonary hypertension in COPD.;Secondary Objective: A secondary objective will be the storage of blood samples in the biobank for further investigation.;Primary end point(s): The primary endpoint in this study will be the change of pulmonary vascular resistance, measured by right heart catheterization, in patients with overlap syndrome after treatment with roflumilast.;Timepoint(s) of evaluation of this end point: The primary endpoint in this study will be measured after a 6-month treatment with roflumilast.	—

Measure

Time frame

Main Objective: Our aim is to investigate if there is a measurable effect of roflumilast in patients suffering from overlap syndrome and pulmonary hypertension, who receive a sequential combination therapy of roflumilast as a potent PDE4 inhibitor and nocturnal non-invasive ventilation as add-on therapy. This pilot study could provide a rationale data for further studies addressing the role of PDE4 inhibitors and other novel anti-inflammatory drugs as a new potential treatment option for pulmonary hypertension in COPD.;Secondary Objective: A secondary objective will be the storage of blood samples in the biobank for further investigation.;Primary end point(s): The primary endpoint in this study will be the change of pulmonary vascular resistance, measured by right heart catheterization, in patients with overlap syndrome after treatment with roflumilast.;Timepoint(s) of evaluation of this end point: The primary endpoint in this study will be measured after a 6-month treatment with roflumilast.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary endpoints will be changes after treatment with roflumilast and changes after treatment with roflumilast and additional treatment with nocturnal non-invasive ventilation. Measured parameters will be changes of the other right heart catheterization parameters and changes in six-minute walk distance, questionnaires, polysomnographic parameters, lung function parameters including blood gas analysis, clinical chemistry parameters and body weight.;Timepoint(s) of evaluation of this end point: Secondary endpoints will be changes after 6-month treatment with roflumilast and changes after 12 months of roflumilast including 6 months treatment with nocturnal non-invasive ventilation.	—

Measure

Time frame

Secondary end point(s): Secondary endpoints will be changes after treatment with roflumilast and changes after treatment with roflumilast and additional treatment with nocturnal non-invasive ventilation. Measured parameters will be changes of the other right heart catheterization parameters and changes in six-minute walk distance, questionnaires, polysomnographic parameters, lung function parameters including blood gas analysis, clinical chemistry parameters and body weight.;Timepoint(s) of evaluation of this end point: Secondary endpoints will be changes after 6-month treatment with roflumilast and changes after 12 months of roflumilast including 6 months treatment with nocturnal non-invasive ventilation.

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Countries

Austria

Contacts

Public ContactClinical Trials Information

Medical University of Graz

kabor.kovacs@klinikum-graz.at

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026