Oxygen Versus PAP for Sleep Apnea in Heart Failure (OPTIMAL-HF)

Oxygen Versus PAP for Treatment of Sleep Apnea in Chronic Heart Failure

The purpose of this study is to compare three treatment modalities for central, or mixed obstructive and central, sleep apnea in patients with chronic heart failure and reduced ejection fraction. The modalities to be tested are nocturnal supplemental oxygen (NSO) and continuous positive airway pressure (CPAP). The main outcome measures will be left ventricular ejection fraction on echocardiogram and peak oxygen consumption on cardiopulmonary exercise testing.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Sleep Apnea Syndromes
• Intervention / Treatment: Device: Continuous positive airway pressure; Behavioral: Healthy Lifestyle and Sleep Education; Device: Nocturnal supplemental oxygen

Detailed Description

Chronic heart failure (HF) is a highly prevalent disease, with a lifetime risk of approximately 20%. Sleep apnea is a common co-morbid condition, occurring in approximately half of patients with chronic HF, and often has predominantly central or mixed obstructive and central characteristics. Although it is associated with increased mortality in patients with HF, sleep apnea is usually asymptomatic and patients are therefore often unwilling to accept standard therapy with positive airway pressure. At the outset of this study, there were three treatment modalities currently recommended by the American Academy of Sleep Medicine for the treatment of predominantly central sleep apnea in HF patients: nocturnal supplemental oxygen (NSO), continuous positive airway pressure (CPAP) and adaptive servo-ventilation (ASV). Recently, ASV was found to increase mortality in patients with heart failure with reduced ejection fraction and central sleep apnea. There are only limited data on the comparative efficacy and tolerability of these three modalities. The present study is designed to compare these modalities with respect to effects on ventricular function, exercise capacity, and other measures of cardiovascular risk.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

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:

• Veteran receiving care within the Veterans Health Administration healthcare system
• Age 18 years
• Physician diagnosis of chronic heart failure, American Heart Association Stage C-D
• LVEF <45%
• No change in active cardiac medications for 4 weeks prior to randomization
• Ability to provide informed consent
• Moderate to severe central or mixed central and obstructive sleep apnea, defined as an apnea-hypopnea index (AHI) 15 events per hour, with a central AHI >5 events/hour

Exclusion Criteria:

• Hospitalization for acute decompensated HF within previous 30 days
• Hospitalization for myocardial infarction or cardiac surgery within previous 90 days
• Presence of a left ventricular assist device
• History of heart transplantation
• Poorly controlled hypertension (>170/>110)
• Poorly controlled diabetes (HbA1c > 9.0)
• Severe renal failure with estimated glomerular filtration rate <30 ml/min
• Prior stroke with functional impairment or other severe, uncontrolled medical problems that may impair ability to participate in the study exams, based on medical history and review of medical records
• Severe chronic insomnia, with reported usual sleep duration <4 hours
• Severe daytime sleepiness, defined as Epworth Sleepiness Scale score 18 or higher or a report of falling asleep driving during the previous year, and deemed a safety risk by study physician
• Awake resting oxyhemoglobin saturation <89%
• Pregnancy
• Smoking by subject or other person in the subject's bedroom, or other open flame in bedroom
• Current use of a positive airway pressure device (including continuous or bi-level positive airway pressure or adaptive servo-ventilation) or supplemental oxygen therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP; Nocturnal continuous positive airway pressure	Device: Continuous positive airway pressure; Nocturnal continuous positive airway pressure, titrated to minimize apnea-hypopnea index; Other Names: CPAP; Behavioral: Healthy Lifestyle and Sleep Education; A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle; Other Names: HLSE
Experimental: NSO; Nocturnal supplemental oxygen	Behavioral: Healthy Lifestyle and Sleep Education; A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle; Other Names: HLSE; Device: Nocturnal supplemental oxygen; Nocturnal supplemental oxygen, titrated to 2-4 liters/minute with target of eliminating nocturnal hypoxemia; Other Names: NSO
Other: HLSE; Healthy lifestyle and sleep education control	Behavioral: Healthy Lifestyle and Sleep Education; A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle; Other Names: HLSE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction	Standard transthoracic 2-dimensional and Doppler echocardiography will be performed. M-mode measurements of LV dimensions will be performed and analyzed according to the American Society of Echocardiography recommendations and LVEF measured using the modified Simpson's method. Measurement is change from baseline in LVEF.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Oxygen Consumption (VO2 Peak)	Treadmill exercise testing will be performed using a motor-driven treadmill and a modified Naughton protocol, with a lightweight disposable pneumotach device positioned in the participant's mouth interfaced with a metabolic cart. Change in VO2 peak between baseline and final visit will be the co-primary outcome of the study. Secondary outcome measures from cardiopulmonary exercise testing include VO2 at anaerobic threshold and VE/VCO2 slope.	3 months
24-hour Ambulatory Blood Pressure	24-hour blood pressure will be measured using a blood pressure cuff that is connected by rubber tubing to a small pressure monitoring device, programmed to measure BP at 20 minute intervals during the day and 30 minute intervals at night (11 PM to 7 AM) for a period of 24 hours. The investigators will assess 24-hour mean arterial pressure as the primary blood pressure outcome, with additional assessment of nocturnal versus diurnal blood pressure effects.	3 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Daniel J Gottlieb, MD MPH, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2014
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: March 1, 2013
• First Submitted That Met QC Criteria: March 6, 2013
• First Posted (Estimate): March 8, 2013

Study Record Updates

• Last Update Posted (Estimate): January 24, 2023
• Last Update Submitted That Met QC Criteria: December 29, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Heart Failure; Sleep Apnea; Exercise Test; Ventricular Ejection Fraction
• 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
• Other Study ID Numbers: CLIN-008-12S

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: Yes
• product manufactured in and exported from the U.S.: No