Epirubicin for the Treatment of Sepsis & Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 5
- 主要终点
- Number of participants with myelotoxicity
研究概览
简要总结
The study will assess the safety of low doses of epirubicin in sepsis patients. Therefore the study will look for side effects in patients treated with low dose epirubicin compared to control patients.
In animals, low dose epirubicin has been shown to induce tolerance to infection and increase survival in septic mice.
The study will also look for positive effects on organ function in humans. The investigators hypothesize that low-dose epirubicin can be used therapeutically to improve the disease course and lessen mortality of patients with sepsis. In a first step, the investigators aim at proving that low-dose epirubicin can safely be administered to sepsis patients and will perform a dose-escalation multi-center trial.
详细描述
There are two ways for organism to deal with infection. Resistance, which means elimination of infectious microorganisms by the immune system, is widely recognized. It can be supported by antibiotic medication and surgical or interventional drainage of an infectious focus. The other response is tolerance, which means limiting organ damage without fighting the infection itself. Its importance has become more clearly recently, but so far there are no therapeutic interventions to support this mechanism.
Epirubicin is a chemotherapeutic substance used to treat cancer. In animal experiments, it has been shown that doses much lower than the ones used in oncology, can induce tolerance in infected animals. Animals treated with epirubicin survive an infectious dose that kills animals not treated with epirubicin. Before this approach can be studied in a large group of sepsis patients, it is necessary that epirubicin in low doses can be safely used in this population.
Therefore in this study, septic patients will be treated with low doses of epirubicin and systematically assessed for serious side effects. Some patients will be treated with placebo for comparison. The trial will be conducted as a dose escalation study with three groups. This means that the first group of patients will receive only a quarter of the dose shown to be effective in animal experiments. Only if no serious side effects are observed will the dose be increased in the second group and again in the third group.
In addition, the study will look for signs of beneficial effects on organ function in human patients with sepsis, pharmacokinetics of epirubicin in sepsis patients and changes in the inflammatory response.
The investigators hypothesize that low-dose epirubicin can be used therapeutically to improve the disease course and lessen mortality of patients with sepsis. In a first step, the investigators aim at proving that low-dose epirubicin can safely be administered to sepsis patients and will perform a phase IIa dose-escalation multi-center trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study medication is provided in colored infusion bags with additional covers
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
- •admitted to the ICU with sepsis or septic shock, diagnosed within the previous 24 hours
排除标准
- •Leukopenia/Neutropenia/Thrombocytopenia-prior or upon inclusion (Leucocyte Count <4000/μL; Neutrophile/ platelets Count below Lower Limit of Normal).
- •Weight >135 kg/BMI >
- •Active neoplasia.
- •History of chemotherapy.
- •Hypersensitivity to epirubicin
- •History of bone marrow or solid organ transplantation.
- •Immunosuppressive therapy.
- •Acute severe infection within 4 weeks prior to admission (Hospitalization or admission to higher level clinical care facility for infection).
- •Chronic infection.
- •Cardiomyopathy with a documented ejection fraction <30% or AICD (automatic internal cardioverter defibrillator) implantation.
- •Acute liver failure following the European Association for the Study of the Liver definition as International Normalized Ratio (INR) >1.5 and elevation of transaminases > 3 times of the upper normal limit (2).
- •Pregnancy during all trimesters/breast-feeding.
- •Chronic mechanical ventilation dependency.
- •Cystic fibrosis.
- •Concomitant medication with Verapamil or Cimetidine.
- •Prior enrollment in this study.
- •Participation in another clinical intervention trial.
研究组 & 干预措施
Placebo
Administration of NaCl i.v. as placebo once.
干预措施: Placebo (Drug)
Epirubicin Phase I
Administration of epirubicin i.v. 3.75 mg/m2 once.
干预措施: Epirubicin (Drug)
Epirubicin Phase II
Administration of epirubicin i.v. 7.5 mg/m2 once.
干预措施: Epirubicin (Drug)
Epirubicin Phase III
Administration of epirubicin i.v. 15 mg/m2 once.
干预措施: Epirubicin (Drug)
结局指标
主要结局
Number of participants with myelotoxicity
时间窗: Up to 14 days after administration of study drug
Neutropenia or thrombocytopenia of grade 3 or 4 (neutrophiles \<1,000μL or platelets \<50,000/μL) at two consecutive study visits up to day 14 accompanied by neutropenia or thrombocytopenia of grade 2, 3 or 4 (neutrophiles \<1,500μL or platelets \<75,000/μL) at both study visits and accompanied by an IPF (immature platelet fraction) below 2.5% at one or two of the consecutive study visits.
次要结局
- Quality of life assesed by the SF-36 questionaire(At follow up 90 days after administration of study drug)
- "Success" rate(3 days after administration of study drug)
- SOFA score(Up to 14 days after administration of study drug)
- Adverse events(Up to 90 days after administration of study drug)
- Fluid balance and urine output(Up to 14 days after administration of study drug)
- Oxygenation index (paO2/FiO2)(Up to 14 days after administration of study drug)
- Survival at day 14, 28 and 90(14, 28 and 90 days)
- Cardiotoxicity(7 days after administration of study drug)
- Need for respiratory support(Up to 14 days after administration of study drug)
- Need for renal replacement therapy(Up to 14 days after administration of study drug)
- Need for catecholamines and inotropes(Up to 14 days after administration of study drug)