Acute and Long-term Effects of CPAP in OSA

Acute, Intermediate and Long-term Effects of CPAP Therapy in Obstructive Sleep Apnoea: a Two-phase Interventional Trial.

Two-phase interventional non-inferiority trial (phase 1: at least 8 weeks of CPAP; phase 2: 2 weeks of CPAP withdrawal) including 32 patients with moderate to severe OSA to compare the physiological consequences of a short-term CPAP withdrawal to the changes in previously untreated OSA. The trial has been designed as a validation of the CPAP-withdrawal model. Baseline in-laboratory sleep studies will be performed prior to CPAP initiation, after 6-8 weeks on CPAP (treatment effect) and following 2 weeks of CPAP therapy withdrawal (withdrawal effect, effect of OSA recurrence).

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea of Adult
• Intervention / Treatment: Device: Continuous positive airway pressure (CPAP)

Detailed Description

Background and Aim: Obstructive sleep apnoea (OSA) is a prevalent sleep-related breathing disorder. OSA is associated with daytime sleepiness, impaired quality of life, and adverse cardiovascular outcome. OSA can be effectively treated with nocturnal continuous positive airway pressure (CPAP) that restores normal breathing during sleep by preventing upper airway collapse. However, many patients in whom treatment of OSA is indicated are not able to adhere to CPAP, and the consequences of untreated OSA seem to differ between OSA phenotypes. Therefore, treatment alternatives to CPAP and a better understanding of treatment implications in different phenotypes of OSA are important targets in this research field. Thus, effective and controlled study designs are needed to address these research questions. Conventional randomised controlled CPAP trials are limited by low CPAP adherence resulting in an underestimation of the treatment effect. In addition, the impracticability of withholding an effective treatment from symptomatic patients resulting in inclusion of less symptomatic and patients with less severe OSA has limited the conclusions from previous trials. The CPAP therapy withdrawal model was introduced to allow studying the pathophysiological consequences of OSA and treatment effects of CPAP in an effective and controlled way. Optimally treated patients previously diagnosed with OSA established on CPAP therapy are included and undergo a short-term therapy interruption. A therapy withdrawal results in recurrence of OSA and pathophysiological changes can be attributed to OSA in this controlled model. However, it is uncertain whether the consequences of OSA during a short-term CPAP therapy withdrawal are comparable to long-term consequences of untreated OSA.

The aim of this two-phase interventional trial is to assess the effects of intermediate and long-term CPAP therapy as well as acute CPAP therapy withdrawal resulting in OSA recurrence compared to longstanding untreated OSA on cardiovascular and symptom outcomes in moderate and severe OSA. The objective is to study the comparability of conventional CPAP therapy trials with the CPAP withdrawal model in terms of evaluating relevant cardiovascular and patient-centred outcomes in OSA.

The investigators hypothesise that the treatment effect of CPAP in previously treatment-naïve patients with OSA - if adherent to CPAP - will support the same conclusions on OSA pathophysiology and therapy effects as a short-term CPAP withdrawal in treatment-adherent patients having a recurrence of OSA in response to CPAP withdrawal and thus support the use of this effective CPAP withdrawal model to use as future study design in interventional trials in OSA. It is hypothesised that the CPAP withdrawal is non-inferior to conventional CPAP trials in studying the effect on blood pressure and OSA-symptoms.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esther Irene I Schwarz, MD; Phone Number: +41442553828; Email: estherirene.schwarz@usz.ch
• Study Contact Backup: Name: Joël J Herzig; Email: joel.herzig@usz.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Recruiting
    • University Hospital Zürich
    • Contact: Joël J Herzig; Email: joel.herzig@usz.ch
    • Contact: Esther I Schwarz, MD; Phone Number: 0041442553828; Email: estherirene.schwarz@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Untreated moderate or severe OSA with an apnoea-hypopnoea-index (AHI) of ≥ 20/h and an oxygen desaturation index (>3%-dips) of ≥ 20/h in an in-laboratory sleep study
• Epworth Sleepiness Scale Score ≥7/24 points
• Indication for CPAP therapy
• Written informed consent

Exclusion Criteria:

• Moderate or more severe obstructive or restrictive ventilatory disorder (FEV1 or FVC < 70%)
• Heart failure
• Other types of sleep-related breathing disorders, e.g. sleep-associated hypoventilation, central sleep apnoea, Cheyne Stoke's Breathing
• Hypoxic or hypercapnic respiratory failure (awake paO2 < 9 kPa or paCO2 > 6 kPa)
• Active treatment for OSA (CPAP, mandibular advancement device, hypoglossal nerve stimulation)
• Current professional driver or previous sleepiness-related accidents
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm (therapy initiation followed by therapy withdrawal); Continuous positive airway pressure (CPAP)	Device: Continuous positive airway pressure (CPAP); Nocturnal continuous positive airway pressure therapy is the gold standard treatment for symptomatic OSA. It provides positive pressure via a nasal or oronasal mask to prevent upper airway collapse during sleep.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nocturnal systolic blood pressure	Ambulatory blood pressure monitoring (ABPM)	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Epworth Sleepines Scale Score (ESS)	Subjective sleepiness, ESS min-max 0-24 points and ESS >10 indicating pathological daytime sleepiness	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
48h, 24h, diurnal and nocturnal systolic and diastolic blood pressure	ABPM	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Office systolic and diastolic blood pressure	Morning office blood pressure	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
48h, 24h, diurnal, nocturnal and office heart rate	Heart rate from ABPM, office measurement and from sleep studies	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Heart rate variability in the time and frequency domain (CV, RMSSD, pRR50, LF, HF, LF/HF)	Measures of heart rate variability (daytime and nighttime)	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Blood pressure variability (BPV, systolic and diastolic)	BPV from ABPM and beat-to-beat blood pressure measurement	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Baroreflex sensitivity (BRS)	Finometer	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Arterial stiffness	ABPM	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Measures of nocturnal hypoventilation (median and maximal transcutaneous partial pressure of CO2 = tcpCO2)	Sleep study parameters	at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal
Measures of nocturnal hypoxaemia (mean nocturnal oxygen saturation = ¢SpO2)	Sleep study parameters	at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal
Measures of nocturnal hypoxaemia (time spent with SpO2 below 90% = t<90)	Sleep study parameters	at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal
Measures of nocturnal hypoxaemia (hypoxic burden)	Sleep study parameters	at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal
Measures of OSA severity (apnoea-hypopnoea-index)	Sleep study parameters	at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal
Measures of OSA severity (oxygen-desaturation index)	Sleep study parameters	at baseline and at least 8 weeks of CPAP as well as after 2 weeks of CPAP withdrawal
Sleepiness (Stanford Sleepiness Scale (SSS))	Questionnaire; 7-point Likert scale to quantify a patient's sleepiness at the time the questionnaire is completed; highr scores indicate more sleepiness	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Fatigue (fatigue severity scale (FSS))	Questionnaire; 9 items, higher score indicates more fatigue	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Disease-specific quality of life (Functional Outcomes of Sleep Questionnaire (FOSQ))	Questionnaires, Disease-specific quality of life questionnaire to determine functional status in adults; measures are designed to assess the impact of disorders of excessive sleepiness on multiple activities of everyday living and the extent to which these abilities are improved by effective treatment; 30 items; higher scores are better	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Superoxide dismutase	Marker of oxidative stress (U/ml)	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Urinary catecholamines	Epinephrine and norepinephrine in morning urine (nnmol/mmol)	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Pulse rise index (>6 beats per minute)	from nocturnal oximetry	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal
Nocturnal oxymetry measures (¢SpO2, t<90, ODI-3%, ODI-4%)	nocturnal pulse oximetry	at baseline and at 2 and at least 8 weeks of CPAP as well as after 1 and after 2 weeks of CPAP withdrawal

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Esther I Schwarz, MD, University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 10, 2024
• First Submitted That Met QC Criteria: February 17, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: BASEC Nr. 2020-02002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No