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.
- 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: 14.1Level: LLTClassification code 10040976Term: Sleep apnea syndromeSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersMedDRA version: 14.1Level: PTClassification code 10037400Term: Pulmonary hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]MedDRA version: 14.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
- Registration Number
- EUCTR2012-003037-41-AT
- Lead Sponsor
- Medizinische Universität Graz, Universitätsklinik für Innere Medizin, Klinische Abteilung für Lungenkrankheiten
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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) <60% of the predicted value and a ratio of FEV1 to forced vital capacity (FVC) of =70% diagnosed by spirometry. According to the recently published COPD criteria, the inclusion criteria correspond to group B, C and D of the Combined Assessment of COPD test.
Sleep Apnea
Patients with moderate to severe sleep apnea will be included in this study. Thus, according to the American Association of Sleep Medicine (AASM) criteria, which is considered to be the current gold standard, patients with an AHI > 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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>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.<br>
- Secondary Outcome Measures
Name Time Method 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.