Sleep-Disordered Breathing in Chronic Thromboembolic Pulmonary Hypertension

Study Overview
=================
Brief Summary
-----------------
There is evidence for a high prevalence of Sleep Disorder Breathing (SDB) in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Central Sleep Apnea, Cheyne-Stokes Breathing and Obstructive Sleep Apnea appear to occur in CTEPH. However, there is no information on the impact of CTEPH treatment modalities on concomitant SDB. Furthermore, the use of PAP therapy in CTEPH has not yet been investigated. CTEPH is a rare and serious disease and there may be a bidirectional association of SDB and CTEPH. This study plans to investigate the prevalence of SDB in CTEPH and compare it to datasets of large epidemiological studies on SDB. Furthermore, the impact of CTEPH treatment on SDB will be analyzed and CTEPH patients for possible PAP treatment will be defined.

Official Title
-----------------
Sleep-Disordered Breathing in Chronic Thromboembolic Pulmonary Hypertension - a Prospective, Descriptive Cohort Study

Conditions
-----------------
Chronic Thromboembolic Pulmonary Hypertension, Sleep Disordered Breathing

Intervention / Treatment
-----------------
* Drug: Riociguat
* Procedure: Pulmonary Endarteriectomy
* Procedure: Ballon Pulmonary Angioplasty


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recently diagnosed untreated CTEPH NYHA I-III Exclusion Criteria: Age<18 Pulmonary Hypertension other than CTEPH Previous diagnosis of SDB Ongoing PAP treatment Use of nasal oxygen

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pulmonary Endarteriectomy - PEA<br>CTEPH treatment via PEA. This arm includes patients who will receive Pulmonary Endarteriectomy (PEA) according to local CTEPH board recommendation. A standardized polygraphy will be conducted before the PEA - intervention, to obtain information concerning Sleep Disorder Breathing. 6 months after the PEA surgery another polygraphy will be accomplished and the results compared with the first polygraphy and the other arms. If Sleep Disorder Breathing remains, a personalized recommendation on further specific therapy (e.g. nocturnal continuous positive airway pressure ventilation) will be made. | Procedure: Pulmonary Endarteriectomy<br>* Patients will receive Pulmonary Endarteriectomy if they are suitable for this procedure according to the recommendation of the local CTEPH board. Patients must also consent to this surgical procedure.<br>* Other names: PEA;|
| Active Comparator: Balloon Pulmonary Angioplasty - BPA<br>CTEPH treatment via BPA. Patients who are suitable for Balloon Pulmonary Angioplasty (BPA) according to the recommendation of the local CTEPH board (e.g. patients not suitable for Pulmonary Endarteriectomy). A standardized polygraphy will be conducted before the first BPA intervention, to gain information about possible sleep-disordered breathing. 6 months after the first BPA intervention another polygraphy will be accomplished and the results compared with the first polygraphy and the other arms. If Sleep Disorder Breathing remains, a personalized recommendation on further specific therapy (e.g. nocturnal continuous positive airway pressure ventilation) will be made. | Procedure: Ballon Pulmonary Angioplasty<br>* Patients will receive Ballon Pulmonary Angioplasty if they are suitable for this procedure according to the recommendation of the local CTEPH board (e.g. not suitable for PEA). Patients must also consent to this procedure.The BPA will be accomplished in several interventions.<br>* Other names: BPA;|
| Active Comparator: Medical Treatment<br>CTEPH treatment via Medical Treatment. Patients who are inoperable (not suitable for Pulmonary Endarteriectomy) and not eligible for BPA according to the recommendation of the local CTEPH board will get medical treatment with Riociguat. The treatment will be assigned according to the currently valid guidelines (2015 European Respiratory Society / European Society of Cardiology guidelines on the diagnosis and treatment of pulmonary hypertension). A standardized polygraphy will be conducted before the medical treatment starts, another polygraphy will be conducted after 6 months of treatment if Riociguat. The results will be compared with the first polygraphy and the other arms. If Sleep Disorder Breathing remains, a personalized recommendation on further specific therapy (e.g. nocturnal continuous positive airway pressure ventilation) will be made. | Drug: Riociguat<br>* Patients will be treated with Riociguat according to guidelines (2015 ERS/ESC guidelines for the diagnosis and treatment of pulmonary hypertension) and manufacturers recommendation.<br>* Other names: Adempas;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AHI change under CTEPH treatment | Change from baseline AHI (Apnoe-Hypopnoe Index, events/h) after 6 months of CTEPH treatment | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with persisting elevated AHI (= ≥15/h) after CTEPH treatment | Patients with persisting elevated AHI will be assessed for further PAP treatment | Time point: 6 months after the individual start of the CTEPH treatment |