Treatment of Central Sleep Apnoea in Patients With Heart Failure With Nasal High Flow Therapy (nHFT) (RELAX)

Treatment of Central Sleep Apnoea and Cheyne Stokes Respiration in Patients With Heart Failure: Nasal High-flow Oxygen Therapy?

To investigate whether nHFT is an effective treatment for patients with Chronic Heart Failure (CHF) and central sleep apnea (CSA).

This study is a prospective one armed uncontrolled intervention pilot study investigating 4 weeks of nHFT at home in 10 patients with CHF and CSA.

Study Overview

• Status: Terminated
• Conditions: Cheyne-Stokes Respiration; Central Sleep Apnea
• Intervention / Treatment: Device: Nasal high flow oxygen therapy

Detailed Description

Study population: 10 CHF patients with a Left Ventricular Injection Fraction(LVEF)< 45% and CSA/Cheyne Stokes Respiration (CSR) (apnoea/hypopnea index (AHI) > 15/hour); with at least 50% of the total number of events having a central character will be included. Patients with other diseases that will influence the respiratory system negatively during sleep i.e. chronic obstructive pulmonary disease (COPD Global Initiative of Obstructive Lung Diseases (GOLD) class 3 and 4), neuromuscular diseases and thorax cage deformities, as well as patients with CHF and CSA that use another form of treatment for their CSA at the time of inclusion, will be excluded.

Intervention: nHFT will be titrated during a first titration night and used at home during the night for 4 weeks consecutively.

Main study parameters/endpoints:

1. To investigate the effect of nHFT with and without oxygen in reducing the apnoea/hypopnoea index during sleep after 4 weeks use nHFT.
2. To investigate improvements in oxygen desaturation index, sleep quality and sleepiness, physical condition, left ventricular ejection fraction (LVEF), heart beat variability (HRV), N-terminal natriuretic peptide (NTproBNP) after 4 weeks use nHFT .
3. Physiological condition; work of breathing and respiratory drive and measuring mouth-throat pressure.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • Department of Pulmonary diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Moderate to severe CSA/CSR (AHI>15), in which CSA is defined when at least 50% of the apnoeas are central apnoeas
2. Heart failure with reduced ejection fraction, defined as a LVEF < 45% of predicted

Exclusion Criteria:

1. Other diseases affecting respiration during sleep (COPD GOLD 3 or 4, neuromuscular disorders, thorax cage deformities)
2. At the moment of the inclusion, the patient does not have a therapy to treat the CSA, such as continuous positive airway pressure (CPAP), oxygen, bilevel intermittent positive airway pressure (BiPAP) or acetazolamide.

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

Experimental: Nasal high flow oxygen therapy; The patient is hospitalized for one night. Initially patients will start with a flow rate of 10 L/min and when they are asleep during the night 90-minute periods of the following settings will be performed: Moderate flow rate: 20 L/min without additional oxygen (with room air, which means a fractional inspired oxygen (FiO2) of 21%); High flow rate: 40-50 L/min without additional oxygen; Moderate flow rate: 20 L/min with FiO2 of 28% (comparable to the 2 L/min additional oxygen through a nasal cannula); High flow rate: 40-50 L/min with FiO2 of 28%

Device: Nasal high flow oxygen therapy; nHFT will be titrated during a first titration night and used at home during the night for 4 weeks consecutively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of apnea/hypopnea index	the change/reduction in AHI after 4 weeks of treatment with nHFT.	Baseline, 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement physical condition	Exercise tolerance assessed with the 6-minute walking test	Baseline, 4 weeks
Work of breathing	Transdiaphragmatic pressure as a marker of diaphragmatic true work of breathing, measured with the use of oesophageal and gastric balloon catheters	Baseline titration night
Drive to breath	Drive to breath assessed with surface electromyography (EMG) of the respiratory muscles	Baseline titration night, 4 weeks
Sleep latency	Assessed as the the length of time that it takes to accomplish the transition from full wakefulness to sleep, measured by means of electro-encephalogram (ECG) as part of the polysomnography	Baseline, 4 weeks
Cardiac functioning	Left ventricular injection fraction (LVEF),	Baseline, 4 weeks
change in oxygen desaturation index (ODI) during sleep while on nHFT	measured after 4 weeks of home nHFT treatment, as compared to the baseline ODI during spontaneous nocturnal breathing.	Baseline, 4 weeks
Sleep efficiency	The percentage of total time in bed actually spent in sleep, assessed with polysomnography	Baseline, 4 weeks
Total rapid-eye movement (REM) stage sleep cycles recorded	Assessed with polysomnography	Baseline, 4 weeks
Heart rate variability	Heart rate variability will be assessed by 24-uur ECG recordings	Baseline, 4 weeks
N-terminal natriuretic peptide (NTproBNP)	Assessed in venous blood	Baseline, 4 weeks

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Study Director: Marieke Duiverman, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Actual): October 18, 2018
• Study Completion (Actual): October 18, 2018

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 14, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: December 13, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: High flow oxygen therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Heart Failure; Sleep Apnea Syndromes; Apnea; Cheyne-Stokes Respiration; Sleep Apnea, Central
• Other Study ID Numbers: 201700147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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