Effects of Empagliflozin and Continuous Positive Airway Pressure on Sleep, Cardiac Function, Oxidative Stress Markers, and Patient-Reported Outcomes in Adults With Heart Failure and Obstructive Sleep Apnea: A Randomized Controlled Clinical Trial.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Change in Apnea-Hypopnea Index (AHI).
研究概览
简要总结
The goal of this randomized clinical trial was to evaluate the effects of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i) on sleep and cardiac outcomes in adults with heart failure (HF) and obstructive sleep apnea syndrome (OSA). The study also examined how subsequent initiation of continuous positive airway pressure (CPAP) therapy affected sleep and cardiac outcomes, and whether response to treatment differed according to baseline obstructive sleep apnea severity.
The main questions it aims to answer were:
- Does empagliflozin affect sleep apnea severity and nocturnal oxygenation before CPAP initiation?
- Does prior empagliflozin treatment influence the response to subsequent CPAP therapy?
- Does empagliflozin affect oxidative stress markers, including total oxidative status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI)?
- Does CPAP therapy initiation affect cardiac outcomes in both groups?
- Does response to treatment differ according to baseline obstructive sleep apnea severity, including mild, moderate, and severe disease?
Researchers compared participants receiving empagliflozin in addition to background HF therapy with those continuing background HF therapy without empagliflozin to evaluate the effects of empagliflozin.
Participants:
- Were randomly assigned to receive empagliflozin plus background HF pharmacotherapy or background HF pharmacotherapy therapy without empagliflozin
- Underwent sleep studies, transthoracic echocardiography and clinical assessments at baseline, 3 months, and 6 months.
- Provided blood samples for measurement of cardiac biomarkers and oxidative stress markers.
- Completed standardized questionnaires assessing sleep quality and symptoms.
- Initiated CPAP therapy after 3 months and continued treatment until the end of the study.
详细描述
Heart failure and obstructive sleep apnea frequently coexist and are linked through complex pathophysiological mechanisms, including intermittent hypoxemia, sympathetic activation, oxidative stress, and hemodynamic alterations. This bidirectional interaction contributes to disease progression, impaired quality of life, and adverse clinical outcomes. While CPAP remains the standard treatment for OSA, treatment response in patients with coexisting HF is variable, and additional therapeutic strategies targeting both conditions are of clinical interest.
Sodium-glucose cotransporter-2 inhibitors, including empagliflozin, have demonstrated significant cardiovascular benefits in patients with HF. Their mechanisms of action, including osmotic diuresis, reduction in intravascular and interstitial fluid volume, and improvement in cardiac function, may also influence the pathophysiology of OSA, particularly by reducing nocturnal rostral fluid shift and upper airway collapsibility. However, prospective randomized data evaluating the effects of SGLT2i on sleep-disordered breathing in patients with HF and OSA remain limited.
This randomized controlled clinical trial was designed to evaluate the effects of empagliflozin on sleep, cardiac, and biochemical outcomes in adults with coexisting HF and OSA, and to assess the impact of subsequent CPAP therapy. The study incorporated a sequential two-phase design to allow differentiation between the early effects of pharmacological therapy and the later effects of CPAP.
In the first phase (0-3 months), participants were randomly assigned in a 1:1 ratio to receive empagliflozin in addition to background HF therapy or to continue background HF therapy without empagliflozin. This phase was designed to evaluate the isolated effect of empagliflozin on OSA severity, nocturnal oxygenation, cardiac function, and oxidative stress.
In the second phase (3-6 months), CPAP therapy was initiated in all participants, while empagliflozin treatment was continued in the study group. This phase was designed to assess the effect of CPAP therapy in both groups and to explore whether prior exposure to empagliflozin influenced the response to CPAP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This was an open-label study without masking. Objective outcome measures, including sleep study parameters, echocardiographic assessments, and biochemical markers, were used to minimize potential bias.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosed heart failure (HF) on stable guideline-directed medical therapy
- •Obstructive sleep apnea (OSA) confirmed by sleep study (mild, moderate, or severe)
- •No prior treatment with empagliflozin or other sodium-glucose cotransporter-2 inhibitors
- •No prior treatment with continuous positive airway pressure therapy
- •Body mass index (BMI) <40 kg/m²
- •Clinical eligibility for CPAP therapy according to current recommendations
- •Ability to provide written informed consent
排除标准
- •Age <18 years
- •Body mass index (BMI) ≥40 kg/m²
- •Active malignancy
- •Severe renal impairment (estimated glomerular filtration rate <25 mL/min/1.73 m²)
- •Advanced hepatic insufficiency
- •Symptomatic hypotension
- •Clinically significant volume depletion or dehydration
- •Known hypersensitivity to empagliflozin or any component of the study medication
- •Any condition that, in the opinion of the investigator, could interfere with study participation or interpretation of results
研究组 & 干预措施
Empagliflozin + Background Heart Failure Therapy
Participants with HF and OSA initiated empagliflozin at baseline in addition to background heart failure therapy and continued treatment throughout the 6-month study period. During the first phase (0-3 months), the effects of empagliflozin were assessed. Continuous positive airway pressure therapy was initiated after 3 months and continued until the end of the study.
This design allowed evaluation of the isolated effect of empagliflozin before CPAP initiation and assessment of its influence on response to subsequent CPAP therapy.
干预措施: Empagliflozin (Drug)
Empagliflozin + Background Heart Failure Therapy
Participants with HF and OSA initiated empagliflozin at baseline in addition to background heart failure therapy and continued treatment throughout the 6-month study period. During the first phase (0-3 months), the effects of empagliflozin were assessed. Continuous positive airway pressure therapy was initiated after 3 months and continued until the end of the study.
This design allowed evaluation of the isolated effect of empagliflozin before CPAP initiation and assessment of its influence on response to subsequent CPAP therapy.
干预措施: Continuous Positive Airway Pressure (CPAP) (Device)
Background Heart Failure Therapy Without Empagliflozin
Participants continued background heart failure therapy without empagliflozin. Continuous positive airway pressure (CPAP) therapy was initiated after 3 months and continued until the end of the study. This design allowed evaluation of the isolated effect of empagliflozin before CPAP initiation and assessment of its influence on response to subsequent CPAP therapy.
干预措施: Continuous Positive Airway Pressure (CPAP) (Device)
结局指标
主要结局
Change in Apnea-Hypopnea Index (AHI).
时间窗: Baseline, 3 months, and 6 months.
Change in AHI, measured as the number of apnea and hypopnea events per hour of sleep, assessed between baseline and follow-up visits at 3 and 6 months.
次要结局
- Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.(Baseline, 3 months, and 6 months.)
研究者
Agnieszka Polecka
Medical Doctor
Medical University of Bialystok