Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 20
- 主要终点
- Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA)
研究概览
简要总结
The long-term goal is to test the clinical efficacy of senolytic therapies to reduce progression to and severity of sepsis in older patients. The central hypothesis is that a threshold burden of SnCs predisposes to a SASP mediated dysfunctional response to PAMPs, contributing to a disproportionate burden of sepsis in older patients. The study hypothesizes timely treatment with fisetin will interrupt this pathway.
A multicenter, randomized, adaptive allocation clinical trial to identify the most efficacious dose of the senolytic fisetin to reduce the composite cardiovascular, respiratory, and renal sequential organ failure assessment score at 1 week, and predict the probability of success of a definitive phase III clinical trial.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >=65 years
- •Primary diagnosis of acute infection (per investigator judgment)
- •Admission order to the hospital
- •Expected length of stay >=48 hours (per investigator judgment)
排除标准
- •Admission to the ICU
- •Vasopressors, mechanical ventilation, or dialysis
- •Comfort care only
- •Total bilirubin >3X or AST/ALT >4x upper limit of normal
- •eGFR < 25 ml/ min/ 1.73 m2
- •Hemoglobin <7 g/dL; white blood cell count ≤ 2,000/mm3; absolute neutrophil count ≤1 x 10^9/;, or platelet count ≤ 40,000/μL
- •Known HIV, Hepatitis B, or Hepatitis C
- •Invasive fungal infection (per investigator judgment)
- •Uncontrolled effusions or ascites (per investigator judgment)
- •New/active invasive cancer except non-melanoma skin cancers
- •Known hypersensitivity or allergy to Fisetin.
- •Active treatment with potential drug-drug interactions
- •Enrolled in another sepsis clinical trial
研究组 & 干预措施
Fisetin- dose 1
Elderly (>=65 years) patients admitted to the hospital with an acute infection and sequential organ failure assessment score sufficient for a diagnosis of sepsis, will be given the first dose of fisetin.
干预措施: Fisetin-dose 1 (Drug)
Fisetin- dose 2
Elderly (>=65 years) patients admitted to the hospital with an acute infection and sequential organ failure assessment score sufficient for a diagnosis of sepsis, will be given the 2nd does of fisetin.
干预措施: Fisetin-dose 2 (Drug)
Placebo
Elderly (>=65 years) patients admitted to the hospital with an acute infection and sequential organ failure assessment score sufficient for a diagnosis of sepsis will receive placebo treatment.
干预措施: Placebo (Drug)
结局指标
主要结局
Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA)
时间窗: day 7
The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body (neurologic, blood, liver, kidney, and blood pressure/hemodynamics) and assigns a score based on the data obtained in each category. This outcome assesses only the cardiovascular, respiratory, and renal categories of the total SOFA score, and calculates the change from day 0 to day 7.
次要结局
- Total SOFA score(day 7)
- Safety of 2 doses of fisetin in patients with mild sepsis(day 28)
- Days in the ICU(day 28)
- Organ failure free days(day 28)
- Zubrod performance status(day 28)
- SF-12 score(day 28)
- All-cause mortality(Day 28)
- Peripheral CD3+ senescent (SnCs) immune cells(day 7)
- TNF-alpha(day 7)
- Outcome is the relative expression of p16Ink4a in CD3+ cells.(day 28)
- Zubrod performance status(day 7)
- SF-12 score(day 7)