Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Inotrem
- 入组人数
- 355
- 试验地点
- 43
- 主要终点
- Sequential organ failure assessment (SOFA) score
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.
详细描述
All patients with a diagnosis of septic shock will be considered for study participation. All potential study patients will receive standard of care for the treatment of septic shock.
After screening for eligibility, patients meeting all inclusion and no exclusion criterion will be randomized. Patients will be randomized to one of three treatment arms.
Treatment with study drug must be initiated as early as possible, but no later than 24 hours after the onset of septic shock, defined by the start of vasopressor therapy.
Patients will be treated for at least 3 days with study drug. After the first 3 days of treatment, patients still requiring vasopressor will be treated until 24 hours after vasopressor withdrawal with a maximum treatment duration of 5 days.
Patients will be assessed at the End of Study (EoS) visit at day 28. After the last patient's day 28 visit, the study will be analyzed. Additional follow up (FU) visits will be conducted after 90 days, 6 and 12 months.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent
- •Age 18 to 85 years (inclusive)
- •Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years)
- •Organ dysfunction defined as acute change in total SOFA score ≥ 2 points
- •Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation
- •Hyperlactatemia (blood lactate >2 mmol/L or 18 mg/dL).
排除标准
- •Previous episode of septic shock requiring vasopressor administration within current hospital stay
- •Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days
- •Immunosuppressive therapy related to recent (<6 months) transplantation
- •Cancer chemotherapy (<3 months) implying an immunodepression
- •Known HIV infection with low CD4 cell count (<200) for at least 6 months
- •Known pregnancy (positive urine or serum pregnancy test)
- •Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
- •Ongoing documented or suspected endocarditis, history of prosthetic heart valves
- •Prolonged QT syndrome
- •End-stage neurological disease
- •End-stage cirrhosis (Child Pugh Class C)
- •Acute Physiology and Chronic Health Evaluation (APACHE II) score <15 or ≥ 34
- •Home oxygen therapy on a regular basis for > 6 h/day
- •Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
- •Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
- •Moribund patients
- •Decision to limit full care taken before obtaining informed consent
- •Participation in another interventional study in the 3 months prior to randomization
研究组 & 干预措施
nangibotide 1
Treatment with study drug at at dose of 0.3mg/kg/hr
干预措施: nangibotide low dose (Drug)
nangibotide 2
Treatment with study drug at at dose of 1.0mg/kg/hr
干预措施: nangibotide high dose (Drug)
Placebo
Treatment with a matched placebo infusion
干预措施: placebo (Drug)
结局指标
主要结局
Sequential organ failure assessment (SOFA) score
时间窗: day 5
Change of total SOFA score from baseline to day 5 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population)
次要结局
- Sepsis support index (SSI)(day 28)
- Duration of Invasive mechanical ventilation (IMV)(day 28)
- Duration of Renal support(day 28)
- Incidence of secondary infections and post shock antibiotic use(day 28)
- Overall survival up to 12 months(12 months)
- All-cause mortality(12 months)
- Organe support free survival(day 28)
- Septic shock related mortality at day 28(day 28)
- Duration of ICU stay(day 28)
- Overall survival on day 28(day 28)
- Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores(day 1, day 2, day 3, day 4, day 5, day 6 and day 7)
- Duration of Vasopressor use(day 28)
- Alive and organ support free at day 28(day 28)