Treatment of Sleep Related Breathing Disorders in Patients With Pulmonary Hypertension (CSRPH)

Treatment of Sleep Related Breathing Disorders in Patients With Pulmonary Hypertension (CSRPH)

The purpose of this study is to study the differential short-term effect of nocturnal oxygen, acetazolamide tablets and nocturnal non-invasive positive pressure ventilation on symptoms, exercise capacity and nocturnal breathing disturbances in subjects with pulmonary hypertension and sleep related breathing disorders

• Trial with medicinal product

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension; Breathing-Related Sleep Disorder
• Intervention / Treatment: Drug: acetazolamide; Drug: Placebo tablet; Other: Supplemental oxygen; Procedure: Non-invasive ventilation; Other: Room air

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Respiratory Clinic, University Hospital of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• percapillary pulmonary hypertension diagnosed by right heart catheterisation -- stable therapy and clinical condition for at least 4 weeks
• sleep disordered breathing with apnea/hypopnea index > 10 events/h and/or median nocturnal oxygen saturation <90%

Exclusion criteria:

• Pregnancy
• severe daytime hypoxemia (PaO2 < 7.2 kPA)
• patients with predominantly obstructive sleep apnea.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: acetazolamide; 1 week therapy, cross-over design	Drug: acetazolamide; 250 mg bid; Other Names: Diamox
Placebo Comparator: Placebo tablet; One week, cross-over design	Drug: Placebo tablet; Placebo tablet (Mannitol) similar to acetazolamide
Experimental: supplemental oxygen during nights; One week, cross-over design	Other: Supplemental oxygen; Oxygen deliverded by nasal cannula; Other Names: Oxygen concentrator
Experimental: Non-invasive ventilation; One week, cross-over design	Procedure: Non-invasive ventilation; Bi-level non-invasive ventilation via nasal mask
Sham Comparator: room air; room air applied via sham-oxygen-concentrator	Other: Room air; Room air applied via sham oxygen concentrator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exercise capacity	Assessment by the 6 minute walk distance	1 week
Quality of Life	Assessment by the short form of the SF 36 questionnaire	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sleep related breathing disorders	assessed by polysomnography according to standard techniques	1 week
hemodynamics measured by echocardiography	right ventricular dimension right ventricular over right atrial pressure	1 week
venous blood analysis	C reactive protein NT-proBNP IL-6	1 week
Nocturnal oxygen desaturation	Assessed by fingertip puleoxymetry	1 week
arterial blood analysis	oxygenation electrolytes	1 week
Vigilance	Assessed by the MURT test	1 week

Collaborators and Investigators

• Sponsor: University of Zurich

Publications and helpful links

General Publications

• Ulrich S, Fischler M, Speich R, Bloch KE. Sleep-related breathing disorders in patients with pulmonary hypertension. Chest. 2008 Jun;133(6):1375-1380. doi: 10.1378/chest.07-3035. Epub 2008 Mar 13.
• Schumacher DS, Muller-Mottet S, Hasler ED, Hildenbrand FF, Keusch S, Speich R, Bloch KE, Ulrich S. Effect of oxygen and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in precapillary pulmonary hypertension and sleep-disturbed breathing. Chest. 2014 Nov;146(5):1226-1236. doi: 10.1378/chest.14-0495.
• Ulrich S, Keusch S, Hildenbrand FF, Lo Cascio C, Huber LC, Tanner FC, Speich R, Bloch KE. Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized, double-blind, cross-over trial. Eur Heart J. 2015 Mar 7;36(10):615-23. doi: 10.1093/eurheartj/eht540. Epub 2013 Dec 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: January 14, 2011
• First Submitted That Met QC Criteria: August 31, 2011
• First Posted (Estimate): September 1, 2011

Study Record Updates

• Last Update Posted (Estimate): December 12, 2012
• Last Update Submitted That Met QC Criteria: December 11, 2012
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Breathing-Related Sleep Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Neurologic Manifestations; Hypertension; Disease; Sleep Wake Disorders; Respiratory Aspiration; Parasomnias; Hypertension, Pulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: CSRPH