The Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Admissions and Mortality in Patients With Heart Failure and Central Sleep Apnea
Condition: Heart Failure; Central Sleep Apnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Central; Heart Failure
Intervention: Oxygen; Room Air
Intervention description: Active nocturnal oxygen concentrator; Sham nocturnal oxygen concentrator (room air)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 98.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        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.