Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors in Adults with Sepsis: a Feasibility Study for a Multicenter Double-Blind Randomized Placebo-Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Mortality
研究概览
简要总结
Goal of this clinical trial is to examine the safety and efficacy of SGLT2 inhibitors on the clinical outcomes in patients with sepsis. Main study outcomes are as follows:
(i) Primary objective is to examine the efficacy and safety of SGLT2 inhibitors on clinical outcomes in patients with sepsis.
(ii) Secondary objective is to examine the effect of SGLT2 inhibitors on inflammatory markers in patients with sepsis.
详细描述
Sepsis is a leading epidemic in the world, affecting an estimated 48.9 million individuals annually. Patients who develop consequential organ failure requiring admission to the intensive care unit (ICU) has a mortality of up to 42%. In Hong Kong, sepsis was the second most common cause of ICU admission, accounting for 16.9% of the 14,068 patient admissions in 2018. Sepsis has remained as one of the top 10 leading causes of death in Hong Kong in the past decade.
Recent randomized controlled trials evaluating various therapies in sepsis have not yielded encouraging results. Targeted therapeutic options including adjunctive glucocorticoid therapy, intravenous vitamin C, and sepsis bundles have not been associated with improved clinical outcomes in patients with sepsis. Administration of antibiotics for source control has remained as the only treatment proven effective in sepsis for two decades. There is an urgent unmet need to identify therapies that may modulate the adverse outcomes of sepsis.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of medication that reduces reabsorption of glucose from the kidneys by modulating the sodium-glucose cotransporter in the renal tubules. Although originally developed as a drug for type 2 diabetes, subsequent large randomized clinical trials have firmly established the clinical efficacy of SGLT2 inhibitors in improving cardiovascular and renal outcomes, irrespective of diabetes status. Patients who received SGLT2 inhibitors had a 32% relative risk reduction in all-cause mortality, 40% reduction in adverse renal outcomes, and 30% reduction in hospitalization for heart failure, compared with placebo.
The investigators hypothesize that SGLT2 inhibitors, as compared with placebo, will improve clinical outcomes of patients with sepsis who are receiving standard care.
(i) The primary objective is to examine the efficacy and safety of SGLT2 inhibitors on clinical outcomes in patients with sepsis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
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
- •Aged 18 years or above
- •New onset of sepsis within 48 hours defined according to the Sepsis-3 criteria. (≥2 SOFA)
- •Provision of signed and dated informed consent form from participant or surrogate
- •Ability to take and adhere to oral and enteral medication regimen
- •Willingness to comply
排除标准
- •Current or recent use of SGLT2 inhibitors (within 12wks prior to randomization)
- •Impaired renal function
- •Clinically unstable or in refractory hypotension
- •History of ketoacidosis
- •Gastrointestinal surgery or GI absorption / malabsorption disorder
- •Pregnancy
- •Known allergic or hypersensitivity reactions to any SGLT2 inhibitors
- •Treatment with another investigational drug or other interventions within 30 days prior to trial
研究组 & 干预措施
SGLT2 inhibitor empagliflozin
10mg daily from recruitment to hospital discharge
干预措施: Empagliflozin 10 MG (Drug)
Placebo
1 tablet daily from recruitment to hospital discharge
干预措施: Placebo (Drug)
结局指标
主要结局
Mortality
时间窗: 28-day mortality
Patient 28-day mortality
Change in Sequential Organ Failure Assessment (SOFA) score
时间窗: Baseline and day 7 score
Score is based on lab results and clinical data. Higher SOFA scores indicate higher risk of ICU mortality. Lower SOFA scores predicts lower risk of ICU mortality.
次要结局
- Interleukin-6, Interleukin-1 beta, TNF-a, IFN-gamma, Procalcitonin, C-reactive protein(Baseline and day 7)
研究者
Pauline Yeung Ng, MD
Clinical Assistant Professor
Hospital Authority, Hong Kong