Infusion Proof-of-concept Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of FE 202158 in Patients With Vasodilatory Hypotension in Early Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 16
- 主要终点
- Cumulative Dose of Open Label NE.
研究概览
简要总结
The purpose of this trial was to examine the safety and tolerability, pharmacokinetics of FE 202158 and to assess whether it can stabilize blood pressure and reduce vascular (blood vessel) leakage. FE 202158 had previously been tested in healthy volunteers.
详细描述
This was a multi-centre, double-blind, randomized, placebo-controlled, parallel group trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of FE 202158 (using three ascending doses) in patients with vasodilatory hypotension in early septic shock, when given as continuous infusion for up to 7 days.
The trial comprised of three treatment arms where FE 202158 was administered in 1.25 ng, 2.5 ng and 3.75 ng dose, respectively. A placebo arm was also included in the trial where patients received isotonic saline.
Efficacy of FE 202158 was determined by evaluating its ability to maintain mean arterial pressure (MAP) >60 mmHg and its modulating effect on inflammatory markers. Effects of FE 202158 on other variables like vital signs, morbidity, mortality and pulmonary function were also determined.
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, Care Provider, 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
- •Signed informed consent form by the patient or a legal representative according to local regulations
- •Man or woman 18 years of age or older
- •Proven or suspected infection
- •Low blood pressure
- •Signs of decreased circulation in the tissues
- •Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from the day of informed consent to one week after the end of infusion of study medication.
排除标准
- •Present or a history (within the last 5 years) of acute coronary syndrome (myocardial infarction or unstable angina). Patients who have been asymptomatic for 6 months after coronary revascularisation are eligible.
- •Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test.
- •Known or suspected cardiac failure
- •Pregnancy or breastfeeding
- •Any cause of hypotension other than early septic shock
- •Use of vasopressin or terlipressin for blood pressure support during the current hospital admission
- •Proven or suspected acute mesenteric ischemia, as judged by the investigator
- •Known episode of septic shock within 1 month prior to randomisation
- •Underlying chronic heart disease
- •Traumatic brain injury
- •Present hospitalisation with burn injury
- •Symptomatic peripheral vascular disease including Raynaud's syndrome
- •Previously randomized in this trial
- •Intake of an investigational drug within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study)
- •Known participation in another clinical trial
- •Considered by the investigator to be unsuitable to participate in the trial for any other reason
研究组 & 干预措施
FE 202158 1.25
Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min.
FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
干预措施: FE 202158 1.25 (Drug)
FE 202158 2.5
Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min.
FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
干预措施: FE 202158 2.5 (Drug)
FE 202158 3.75
Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 3.75 ng/kg/min.
FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
干预措施: FE 202158 3.75 (Drug)
PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
干预措施: Placebo (Other)
结局指标
主要结局
Cumulative Dose of Open Label NE.
时间窗: Day 1 up to Day 7
Cumulative Dose of Open Label NE over 7 days. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
时间窗: Day 1 up to Day 7
Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
时间窗: Day 1 up to Day 7
Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Infusion Rates of Open Label NE.
时间窗: Day 1 up to Day 7
Mean open label NE infusion rate within each predefined time period. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
次要结局
- Change From Baseline in Interleukin-10 (IL-10)(At Day 1, Day 2, Day 4, and Day 7)
- Percentage of Patients Alive and Free of All Vasopressors(At Day 7, Day 14 and Day 28)
- Percentage of Days Alive and Free of Ventilation(At Day 7)
- PK Parameter in Patients : Time to Steady State(Day 1 up to Day 7)
- Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist(At Day 1, Day 2, Day 4, and Day 7)
- Pulmonary Function : Change From Baseline in PaO2/FiO2(Day 1 up to Day 7)
- Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration(Day 1 up to Day 7)
- PK Parameter in Patients : Clearance(Day 1 up to Day 7)
- PK Parameter in Patients : Terminal Elimination Half-life(Day 1 up to Day 7)
- Change From Baseline in C-reactive Protein (CRP)(Day 1 up to Day 7)
- Change From Baseline in Interleukin-6 (IL-6)(At Day 1, Day 2, Day 4, and Day 7)
- PK Parameter in Patients : Steady State Volume of Distribution(Day 1 up to Day 7)
- PK Parameter in Patients : Initial Elimination Half-life(Day 1 up to Day 7)
- Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha(At Day 1, Day 2, Day 4, and Day 7)
- SOFA Score(Day 1 up to Day 7, Day 14 and Day 29)
- Days Alive and Free of Any Organ Dysfunction at Day 7(At Day 7)
- Mortality(At Day 1, 7, 14, and 28)
- Incidence of Abnormal Changes in ECG(Day 1 up to Day 7)
- Change From Baseline in Heart Rate(Day 1 up to Day 7)
- Change From Baseline in Fluid Balance(Day 1 up to Day 7)
- Change From Baseline in Arterial Blood Gas (Lactate)(Day 1 up to Day 7)
- Pulmonary Function : Change From Baseline in Tidal Volume(Day 1 up to Day 7)
- Percentage of Days Alive and Free of Dialysis(At Day 7, Day 14 and Day 28)