The Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Admissions and Mortality in Patients With Heart Failure and Central Sleep Apnea

Heart Failure Clinical Trial

Official title:

The Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Admissions and Mortality in Patients With Heart Failure and Central Sleep Apnea (LOFT-HF)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03745898
• Other study ID #: U24HL140412-01_UG3
• Secondary ID: U24HL140412-01
• Status: Terminated
• Phase: Phase 3
• Start date: April 15, 2019
• Est. completion date: June 17, 2022

Study information

• Verified date: July 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to evaluate the long-term effects of Nocturnal Oxygen Therapy (NOXT) on the mortality and morbidity of patients with stable heart failure and a reduced ejection fraction (HFrEF), already receiving optimal guideline-directed medical therapy (GDMT), who have central sleep apnea (CSA).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 98
• Est. completion date: June 17, 2022
• Est. primary completion date: June 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Aged = 21 years at the date of consent.
• History of chronic, stable heart failure with reduced ejection fraction with left ventricular ejection fraction (LVEF) = 50% determined by echocardiography, radionuclide angiography, left ventriculography, or cardiac magnetic resonance imaging, within the year prior to enrollment.
• Central sleep apnea, defined using as an apnea-hypopnea index (AHI) > 15/h with = 50% central events (apnea and hypopneas).
• New York Heart Association (NYHA) Class III or IV, or NYHA Class II with any of the

following:

1. at least one hospitalization for heart failure within the 24 months prior to enrollment or;

2. a BMI corrected BNP = 300 pg/ml or a corrected NT-proBNP = 1500 pg/ml or;

3. an ED visit for HF exacerbation where the patient has received an IV diuretic within 12 months of enrollment.

• Treatment with stable, optimized guideline-directed medical therapies (GDMT) according to applicable guidelines in the U.S. and Canada, where stable is defined as the addition of no new class of disease-modifying drug for = 30 days prior to randomization (reasons for intolerance to GDNT must be documented).
• In the investigator's opinion, willing and able to comply with all study requirements.
• Able to fully understand study information and sign an Institutional Review Board (IRB) approved informed consent (including HIPAA authorization in the U.S.).

Exclusion Criteria:

• Current positive airway pressure use or predominantly obstructive rather than central sleep apnea.
• Oxygen saturation < 90% at rest during the day.
• Nocturnal oxygen saturation < 88% for > 5 continuous minutes unaccompanied by apneas or hypopneas.
• Chronic daytime or nighttime use of supplemental oxygen.
• Participants and their bed-partners who currently smoke in the bedroom.
• Severe pulmonary disease requiring continuous home oxygen therapy or the continuous or frequent intermittent use of oral steroids or documented severe chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) < 50%.
• Cardiac surgery, percutaneous coronary intervention, myocardial infarction or unstable angina within the previous 3 months.
• Transient ischemic attack or stroke within the previous 3 months.
• Cardiac resynchronization therapy implantation scheduled or performed within 3 months prior to randomization.
• Primary hemodynamically-significant uncorrected valvular heart disease (obstructive or regurgitant) or any valvular disease expected to require surgery during the trial.
• Acute myocarditis/pericarditis or other cause of potentially reversible cardiomyopathy (e.g., post-partum cardiomyopathy, tachycardia-induced cardiomyopathy), within the previous 6 months.
• End-stage (Stage D) heart failure (HF) requiring continuous outpatient intravenous (IV) inotropic therapy, placement of ventricular assist device, listing for cardiac transplantation, or end-of-life care (e.g. hospice care).
• Pregnancy or of child bearing potential without a negative pregnancy test within 10 days prior to enrollment.
• Life expectancy < 1 year for diseases unrelated to chronic HF.
• Enrolled or planning to enroll in another study that may conflict with protocol requirements or confound subject results in this trial.

Related Conditions & MeSH terms

• Apnea
• Central Sleep Apnea
• Heart Failure
• Sleep Apnea Syndromes
• Sleep Apnea, Central

Intervention

Drug:
• Oxygen
Active nocturnal oxygen concentrator

Other:
• Room Air
Sham nocturnal oxygen concentrator (room air)

Locations

Country	Name	City	State
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Miami	Coral Gables	Florida
United States	Wayne State University	Detroit	Michigan
United States	University Hospitals	Highland Hills	Ohio
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Saint Luke's Mid America Health Institute	Kansas City	Kansas
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	Yale School of Medicine	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Washington	Seattle	Washington
United States	Stanford University	Stanford	California
United States	University of Arizona	Tucson	Arizona
United States	Main Line Health	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Ohio State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First Occurrence of Mortality Due to Any Cause or an Unplanned Hospitalization for Worsening Heart Failure or a Life-saving Cardiovascular (CV) Intervention	This is a composite primary outcome	12 months
Secondary	Recurrent Event Analyses of Mortality and Morbidity	Count of occurrences of mortality due to any cause or an unplanned hospitalization for worsening heart failure or a Life-saving Cardiovascular (CV) Intervention. (Death, Hospitalization HF / Outpatient HF, Myocardial Infarction / Unstable Angina, Resuscitated Cardiac Arrest, Stroke)	From enrollment to study termination, attrition or death. Min = 41 days, Max = 626 Days
Secondary	Quality of Life and Symptoms - HF Disease-specific Quality of Life	HF disease-specific quality of life will be assessed by the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life for those who have heart failure. An overall summary score is derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	Baseline, 6 month follow up
Secondary	Quality of Life and Symptoms - Generic-quality of Life	Generic-quality of life will be assessed by the change in the Euroqol - 5 Dimensions (EQ-5D) questionnaire. The questionnaire comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. A total score in calculated using a US-specific weighted algorithm with a possible range [-0.109,1], where 1 represents the best outcome with 'no problems' selected for every item on the scale.	Baseline, 6 month follow up
Secondary	Quality of Life and Symptoms - Depressive Symptoms	Depressive symptoms will be assessed by the change in the Patient Health Questionnaire - 8 items (PHQ-8). A scores ranges from 0 to 24. A score greater than 10 is considered major depression and a score 20 or more is considered severe major depression.	Baseline, 6 month follow up
Secondary	Quality of Life and Symptoms - Sleep Symptoms and Sleep Related Daytime Impairment	Sleep symptoms and sleep related daytime impairment will be assessed by the change in the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) Questionnaire and Sleep Related Impairment (SRI) Questionnaire. The final score for each is represented by the T-score, a standardized score with a population mean of 50 and a standard deviation (SD) of 10, where a higher score indicates a worse score. For SRI a T-score >= 60 implies high levels of sleep related impairment, and for PROMIS SD a T-score >= 60 implies high levels of sleep disturbance.	Baseline, 6 month follow up
Secondary	Functional Status	Functional status will be assessed by the change in New York Heart Association (NYHA) Functional Class Ranking, where higher classes indicate decreased function (worse outcome). Possible Classes are I-IV, which indicate a score of 1-4. Class I indicates No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. ; Class II indicates Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. ; Class III indicates Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. ; and Class IV indicates Symptoms of heart failure at rest. Any physical activity causes further discomfort.	Baseline, 6 month follow up