The Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Admissions and Mortality in Patients With Heart Failure and Central Sleep Apnea
Study Details
Study Description
Brief 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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Nocturnal Oxygen Therapy Active nocturnal oxygen therapy |
Drug: Oxygen
Active nocturnal oxygen concentrator
|
Sham Comparator: Sham Nocturnal Oxygen Therapy Sham nocturnal oxygen therapy (room air) |
Other: Room Air
Sham nocturnal oxygen concentrator (room air)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- First occurrence of mortality due to any cause or an unplanned hospitalization for worsening heart failure or a life-saving cardiovascular (CV) intervention [Through study completion, an average of 2.5 years]
This is a composite primary outcome
Secondary Outcome Measures
- Recurrent event analyses of morbidity [Through study completion, an average of 2.5 years]
- Recurrent event analyses of mortality [Through study completion, an average of 2.5 years]
- Quality of Life and Symptoms - HF disease-specific quality of life [12 months]
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.
- Quality of Life and Symptoms - Generic-quality of life [12 months]
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. There is no total score or range.
- Quality of Life and Symptoms - Depressive symptoms [12 months]
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.
- Quality of Life and Symptoms - Sleep symptoms and sleep related daytime impairment [12 months]
Sleep symptoms and sleep related daytime impairment will be assessed by the change in the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Sleep Related Impairment Questionnaires. Scores range from 8 - 40. The final score is represented by the T-score, a standardized score with a mean of 50 and a standard deviation (SD) of 10.
- Functional Status [12 months]
Functional status will be assessed by the change in New York Heart Association (NYHA) Functional Class Ranking
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged ≥ 21 years at the date of consent.
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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.
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Central sleep apnea, defined using as an apnea-hypopnea index (AHI) > 15/h with ≥ 50% central events (apnea and hypopneas).
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New York Heart Association (NYHA) Class III or IV, or NYHA Class II with any of the following:
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at least one hospitalization for heart failure within the 24 months prior to enrollment or;
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a BMI corrected BNP ≥ 300 pg/ml or a corrected NT-proBNP ≥ 1500 pg/ml or;
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an ED visit for HF exacerbation where the patient has received an IV diuretic within 12 months of enrollment.
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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).
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In the investigator's opinion, willing and able to comply with all study requirements.
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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:
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Current positive airway pressure use or predominantly obstructive rather than central sleep apnea.
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Oxygen saturation < 90% at rest during the day.
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Nocturnal oxygen saturation < 88% for > 5 continuous minutes unaccompanied by apneas or hypopneas.
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Chronic daytime or nighttime use of supplemental oxygen.
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Participants and their bed-partners who currently smoke in the bedroom.
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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%.
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Cardiac surgery, percutaneous coronary intervention, myocardial infarction or unstable angina within the previous 3 months.
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Transient ischemic attack or stroke within the previous 3 months.
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Cardiac resynchronization therapy implantation scheduled or performed within 3 months prior to randomization.
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Primary hemodynamically-significant uncorrected valvular heart disease (obstructive or regurgitant) or any valvular disease expected to require surgery during the trial.
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Acute myocarditis/pericarditis or other cause of potentially reversible cardiomyopathy (e.g., post-partum cardiomyopathy, tachycardia-induced cardiomyopathy), within the previous 6 months.
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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).
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Pregnancy or of child bearing potential without a negative pregnancy test within 10 days prior to enrollment.
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Life expectancy < 1 year for diseases unrelated to chronic HF.
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Enrolled or planning to enroll in another study that may conflict with protocol requirements or confound subject results in this trial.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University of Arizona | Tucson | Arizona | United States | 85721 |
2 | Stanford University | Stanford | California | United States | 94305 |
3 | Yale School of Medicine | New Haven | Connecticut | United States | 06510 |
4 | University of Miami | Coral Gables | Florida | United States | 33124 |
5 | Northwestern University Feinberg School of Medicine | Chicago | Illinois | United States | 60611 |
6 | University of Chicago | Chicago | Illinois | United States | 60637 |
7 | Saint Luke's Mid America Health Institute | Kansas City | Kansas | United States | 64111 |
8 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
9 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
10 | Wayne State University | Detroit | Michigan | United States | 48217 |
11 | Washington University in St. Louis | Saint Louis | Missouri | United States | 63130 |
12 | University of New Mexico School of Medicine | Albuquerque | New Mexico | United States | 87131 |
13 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 11029 |
14 | University of Cincinnati | Cincinnati | Ohio | United States | 45220 |
15 | MetroHealth Medical Center | Cleveland | Ohio | United States | 44109 |
16 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
17 | Ohio State University | Columbus | Ohio | United States | 43202 |
18 | University Hospitals | Highland Hills | Ohio | United States | 44122 |
19 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
20 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15260 |
21 | Main Line Health | Wynnewood | Pennsylvania | United States | 19096 |
22 | University of Texas Health Science Center at Houston | Houston | Texas | United States | 77030 |
23 | University of Utah | Salt Lake City | Utah | United States | 84112 |
24 | University of Virginia | Charlottesville | Virginia | United States | 22904 |
25 | University of Washington | Seattle | Washington | United States | 98195 |
26 | University of Wisconsin-Madison | Madison | Wisconsin | United States | 53706 |
Sponsors and Collaborators
- Brigham and Women's Hospital
- Ohio State University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- U24HL140412-01_UG3
- U24HL140412-01