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

NCT03745898 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: U24HL140412-01_UG3U24HL140412-01
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 26

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).

Conditions

Heart Failure; Central Sleep Apnea

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Recurrent Event Analyses of Mortality and Morbidity

  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

  Baseline, 6 month follow up

• Quality of Life and Symptoms - Generic-quality of Life

  Baseline, 6 month follow up

• Quality of Life and Symptoms - Depressive Symptoms

  Baseline, 6 month follow up

• Quality of Life and Symptoms - Sleep Symptoms and Sleep Related Daytime Impairment

  Baseline, 6 month follow up

Study Arms (2)

Nocturnal Oxygen Therapy

ACTIVE COMPARATOR

Active nocturnal oxygen therapy

Drug: Oxygen

Sham Nocturnal Oxygen Therapy

SHAM COMPARATOR

Sham nocturnal oxygen therapy (room air)

Other: Room Air

Interventions

Oxygen DRUG

Active nocturnal oxygen concentrator

Nocturnal Oxygen Therapy

Room Air OTHER

Sham nocturnal oxygen concentrator (room air)

Also known as: Sham Oxygen

Sham Nocturnal Oxygen Therapy

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Ohio State University: collaborator

Study Sites (26)

University of Arizona

Tucson, Arizona, 85721, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

University of Miami

Coral Gables, Florida, 33124, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Saint Luke's Mid America Health Institute

Kansas City, Kansas, 64111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Wayne State University

Detroit, Michigan, 48217, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

University of New Mexico School of Medicine

Albuquerque, New Mexico, 87131, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 11029, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45220, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43202, United States

Location

University Hospitals

Highland Hills, Ohio, 44122, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15260, United States

Location

Main Line Health

Wynnewood, Pennsylvania, 19096, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53706, United States

Location

Related Publications (1)

• 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.

  PMID: 40929650 DERIVED

MeSH Terms

Conditions

Heart Failure; Sleep Apnea, Central

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Limitations and Caveats

Study incomplete due to early termination

Results Point of Contact

• Title: Dr. Susan Redline
• Organization: Brigham and Women's Hospital

sredline@bwh.harvard.edu

(617) 732-5500

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Senior Physician

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 19, 2018
• Study Start: April 15, 2019
• Primary Completion: June 17, 2022
• Study Completion: June 17, 2022
• Last Updated: August 1, 2023
• Results First Posted: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

US (26)