Heart FailurePhase 3NCT03745898
The Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Admissions and Mortality in Patients With Heart Failure and Central Sleep Apnea
A Phase 3 study testing Oxygen and Room Air in people with Heart Failure and Central Sleep Apnea, run by Brigham and Women's Hospital at 26 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Heart Failure, Central Sleep Apnea
- What is being tested?
- Oxygen and Room Air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 26 sitesUnited States
- Study dates
- 15 Apr 2019to 17 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- at least one hospitalization for heart failure within the 24 months prior to enrollment or;
- 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.
- 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.).
Who cannot join
- 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%.
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- 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.
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
United States26 sites
University of New Mexico School of Medicine
Albuquerque, New Mexico, 87131
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Virginia
Charlottesville, Virginia, 22904
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45220
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43202
University of Miami
Coral Gables, Florida, 33124
Wayne State University
Detroit, Michigan, 48217
University Hospitals
Highland Hills, Ohio, 44122
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Saint Luke's Mid America Health Institute
Kansas City, Kansas, 64111
University of Wisconsin-Madison
Madison, Wisconsin, 53706
Yale School of Medicine
New Haven, Connecticut, 06510
Icahn School of Medicine at Mount Sinai
New York, New York, 11029
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15260
Oregon Health & Science University
Portland, Oregon, 97239
University of Utah
Salt Lake City, Utah, 84112
University of Washington
Seattle, Washington, 98195
Washington University in St. Louis
St Louis, Missouri, 63130
Stanford University
Stanford, California, 94305
University of Arizona
Tucson, Arizona, 85721
Main Line Health
Wynnewood, Pennsylvania, 19096
About this study
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)
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).
- Conditions
- Heart Failure, Central Sleep Apnea
- Being tested
- Oxygen, Room Air
- Medical subject headings
- Heart Failure, Sleep Apnea, Central
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxygenDrug
Active nocturnal oxygen concentrator
Room AirOther
Also called Sham Oxygen
Sham nocturnal oxygen concentrator (room air)
| Study group | Role | What they receive |
|---|---|---|
| Nocturnal Oxygen Therapy | Active comparator | Active nocturnal oxygen therapy Receives: Drug: Oxygen |
| Sham Nocturnal Oxygen Therapy | Sham comparator | Sham nocturnal oxygen therapy (room air) Receives: Other: Room Air |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (6)
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)
Measured: From enrollment to study termination, attrition or death. Min = 41 days, Max = 626 Days
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.
Measured: Baseline, 6 month follow up
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.
Measured: Baseline, 6 month follow up
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.
Measured: Baseline, 6 month follow up
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.
Measured: Baseline, 6 month follow up
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.
Measured: Baseline, 6 month follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start15 Apr 2019
- Primary completion17 Jun 2022
- Study completion17 Jun 2022
Why it stopped: Low feasibility of completion within the study period due to delayed site activation and slow participant accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ohio State University
- Responsible party
- Principal investigator, Susan Redline, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03745898
- Sponsor's protocol ID
- U24HL140412-01_UG3
- Other IDs
- U24HL140412-01
- Status last verified
- Jul 2023
- First submitted
- 9 Nov 2018
- Last updated
- 1 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All relevant deidentified data will be deposited in Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) and the National Sleep Research Resource (NSRR)
Publications
Redline S, Li D, Javaheri S, Patel SR, Parthasarathy S, Fang JC, Brown LK, Dunlap M, Badr MS, Shah N, Chi L, Majid R, Teodorescu M, Stewart G, Hsich E, Polonsky T, Vader J, Johnson MR, Auckley D, Yaggi HK, Kao A, Azarbarzin A, Alex R, Rueschman M, Wolfe L, Gottlieb DJ, Sands SA, Zee PC, Mehra R, Mokhlesi B, Khayat R, Lewis EF, Abraham WT, Wang R. Nocturnal Oxygen Therapy for Central Sleep Apnea in Patients with Heart Failure: A Multisite, Double-Blind, Sham-controlled Randomized Clinical Trial (LOFT-HF). Ann Am Thorac Soc. 2025 Dec;22(12):1951-1960. doi: 10.1513/AnnalsATS.202504-409OC.
PubMed 40929650
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03745898
- Acronym / sponsor ID
- U24HL140412-01_UG3
- Conditions
- Heart Failure, Central Sleep Apnea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low feasibility of completion within the study period due to delayed site activation and slow participant accrual
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Ohio State University
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 17 Jun 2022 (actual)
- Study completion
- 17 Jun 2022 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Posted 1 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nocturnal Oxygen Therapy | Active comparator | Drug: OxygenActive nocturnal oxygen therapy |
| Sham Nocturnal Oxygen Therapy | Sham comparator | Other: Room AirSham nocturnal oxygen therapy (room air) |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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).
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxygenActive nocturnal oxygen concentrator | Drug | Nocturnal Oxygen Therapy |
| Room AirAlso: Sham OxygenSham nocturnal oxygen concentrator (room air) | Other | Sham Nocturnal Oxygen Therapy |
Primary outcome
First Occurrence of Mortality Due to Any Cause or an Unplanned Hospitalization for Worsening Heart Failure or a Life-saving Cardiovascular (CV) Intervention
Time frame: 12 months
This is a composite primary outcome
6 secondary outcomes
Recurrent Event Analyses of Mortality and Morbidity
Time frame: From enrollment to study termination, attrition or death. Min = 41 days, Max = 626 Days
Quality of Life and Symptoms - HF Disease-specific Quality of Life
Time frame: Baseline, 6 month follow up
Quality of Life and Symptoms - Generic-quality of Life
Time frame: Baseline, 6 month follow up
Quality of Life and Symptoms - Depressive Symptoms
Time frame: Baseline, 6 month follow up
Quality of Life and Symptoms - Sleep Symptoms and Sleep Related Daytime Impairment
Time frame: Baseline, 6 month follow up
Functional Status
Time frame: Baseline, 6 month follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40929650Redline S, Li D, Javaheri S, Patel SR, Parthasarathy S, Fang JC, Brown LK, Dunlap M, Badr MS, Shah N, Chi L, Majid R, Teodorescu M, Stewart G, Hsich E, Polonsky T, Vader J, Johnson MR, Auckley D, Yaggi HK, Kao A, Azarbarzin A, Alex R, Rueschman M, Wolfe L, Gottlieb DJ, Sands SA, Zee PC, Mehra R, Mokhlesi B, Khayat R, Lewis EF, Abraham WT, Wang R. Nocturnal Oxygen Therapy for Central Sleep Apnea in Patients with Heart Failure: A Multisite, Double-Blind, Sham-controlled Randomized Clinical Trial (LOFT-HF). Ann Am Thorac Soc. 2025 Dec;22(12):1951-1960. doi: 10.1513/AnnalsATS.202504-409OC.
- Individual participant dataSharing planned: Yes. All relevant deidentified data will be deposited in Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) and the National Sleep Research Resource (NSRR)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oxygen and Room Air in people with Heart Failure and Central Sleep Apnea, run by Brigham and Women's Hospital at 26 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First Occurrence of Mortality Due to Any Cause or an Unplanned Hospitalization for Worsening Heart Failure or a Life-saving Cardiovascular (CV) Intervention (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03745898, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.