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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03745898

Enrollment

Registered

2018-11-19

Start date

2019-04-15

Completion date

2022-06-17

Last updated

2023-08-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure, Central Sleep Apnea

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).

Interventions

DRUGOxygen

Active nocturnal oxygen concentrator

OTHERRoom Air

Sham nocturnal oxygen concentrator (room air)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
First Occurrence of Mortality Due to Any Cause or an Unplanned Hospitalization for Worsening Heart Failure or a Life-saving Cardiovascular (CV) Intervention	12 months	This is a composite primary outcome

Secondary

Measure	Time frame	Description
Quality of Life and Symptoms - HF Disease-specific Quality of Life	Baseline, 6 month follow up	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	Baseline, 6 month follow up	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.
Recurrent Event Analyses of Mortality and Morbidity	From enrollment to study termination, attrition or death. Min = 41 days, Max = 626 Days	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)
Quality of Life and Symptoms - Sleep Symptoms and Sleep Related Daytime Impairment	Baseline, 6 month follow up	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.
Functional Status	Baseline, 6 month follow up	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.
Quality of Life and Symptoms - Depressive Symptoms	Baseline, 6 month follow up	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Nocturnal Oxygen Therapy Active nocturnal oxygen therapy Oxygen: Active nocturnal oxygen concentrator	48
Sham Nocturnal Oxygen Therapy Sham nocturnal oxygen therapy (room air) Room Air: Sham nocturnal oxygen concentrator (room air)	50
Total	98

Baseline characteristics

Characteristic	Sham Nocturnal Oxygen Therapy	Total	Nocturnal Oxygen Therapy
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	22 Participants	35 Participants	13 Participants
Age, Categorical Between 18 and 65 years	28 Participants	63 Participants	35 Participants
Age, Continuous	62.78 years STANDARD_DEVIATION 11.12	61.69 years STANDARD_DEVIATION 11.67	60.56 years STANDARD_DEVIATION 12.22
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	10 Participants	28 Participants	18 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	3 Participants	1 Participants
Race (NIH/OMB) White	37 Participants	66 Participants	29 Participants
Region of Enrollment United States	50 Participants	98 Participants	48 Participants
Sex: Female, Male Female	11 Participants	23 Participants	12 Participants
Sex: Female, Male Male	39 Participants	75 Participants	36 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	6 / 48	6 / 50
other Total, other adverse events	6 / 48	5 / 50
serious Total, serious adverse events	26 / 48	22 / 50

Outcome results

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

Time frame: 12 months

Population: Recruitment incomplete due to early termination

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Nocturnal Oxygen Therapy	First Occurrence of Mortality Due to Any Cause or an Unplanned Hospitalization for Worsening Heart Failure or a Life-saving Cardiovascular (CV) Intervention	15 Participants
Sham Nocturnal Oxygen Therapy	First Occurrence of Mortality Due to Any Cause or an Unplanned Hospitalization for Worsening Heart Failure or a Life-saving Cardiovascular (CV) Intervention	9 Participants

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.

Time frame: Baseline, 6 month follow up