Effects of the V1a Agonist FE 202158 in Patients With Septic Shock
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
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Bispebjerg、丹麦
- Bispebjerg Hospital
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Copenhagen、丹麦
- Rigshospitalet
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Hillerød、丹麦
- Hillerød Hospital
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Hvidovre、丹麦
- Hvidovre Hospital
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Vancouver、加拿大
- Royal Columbian Hospital
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Vancouver、加拿大
- St. Paul´s Hospital
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Brussels、比利时
- Clinique Universitaire St-Luc
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Brussels、比利时
- Erasme Hospital (Free University of Brussels)
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Brussels、比利时
- University Hospital Vrije Universiteit
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Dinant、比利时
- Service des Soins Intensits
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Delaware
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Newark、Delaware、美国
- Christiana Care Health System
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Massachusetts
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Springfield、Massachusetts、美国
- Baystate Medical Center
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Minnesota
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Duluth、Minnesota、美国
- Division of Education and Research SMDC Health System
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New Jersey
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Camden、New Jersey、美国
- Cooper University Hospital
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New York
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New York、New York、美国
- Mount Sinai School of Medicine
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Texas
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Houston、Texas、美国
- Baylor College of Medicine
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：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. |
FE 202158 at dose 1.25 ng/kg/min infused.
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实验性的：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. |
FE 202158 at dose 2.5 ng/kg/min infused.
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实验性的：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. |
FE 202158 at dose 3.75 ng/kg/min infused.
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安慰剂比较：PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
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Isotonic saline infused.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
大体时间：Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
大体时间：Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Cumulative Dose of Open Label NE.
大体时间：Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Infusion Rates of Open Label NE.
大体时间：Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
大体时间：Day 1 up to Day 7
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PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. 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. |
Day 1 up to Day 7
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PK Parameter in Patients : Time to Steady State
大体时间：Day 1 up to Day 7
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PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. 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. |
Day 1 up to Day 7
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PK Parameter in Patients : Clearance
大体时间：Day 1 up to Day 7
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PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. 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. |
Day 1 up to Day 7
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PK Parameter in Patients : Steady State Volume of Distribution
大体时间：Day 1 up to Day 7
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PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. 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. |
Day 1 up to Day 7
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PK Parameter in Patients : Initial Elimination Half-life
大体时间：Day 1 up to Day 7
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PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. 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. |
Day 1 up to Day 7
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PK Parameter in Patients : Terminal Elimination Half-life
大体时间：Day 1 up to Day 7
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PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. 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. |
Day 1 up to Day 7
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Change From Baseline in C-reactive Protein (CRP)
大体时间：Day 1 up to Day 7
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The change from Baseline in CRP levels were analysed and presented as per the planned time points. 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. |
Day 1 up to Day 7
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Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha
大体时间：At Day 1, Day 2, Day 4, and Day 7
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The change from Baseline in TNF-alpha levels were analysed and presented as per the planned time points. 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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Interleukin-6 (IL-6)
大体时间：At Day 1, Day 2, Day 4, and Day 7
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The change from Baseline in IL-6 levels were analysed and presented as per the planned time points. 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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Interleukin-10 (IL-10)
大体时间：At Day 1, Day 2, Day 4, and Day 7
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The change from Baseline in IL-10 levels were analysed and presented as per the planned time points. 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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist
大体时间：At Day 1, Day 2, Day 4, and Day 7
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The change from Baseline in IL-1R levels were analysed and presented as per the planned time points. 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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Heart Rate
大体时间：Day 1 up to Day 7
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The change from Baseline in heart rate was analysed and presented as per the planned time points. 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. |
Day 1 up to Day 7
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Change From Baseline in Fluid Balance
大体时间：Day 1 up to Day 7
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The change from Baseline in fluid balance were analysed and presented as per the planned time points. The fluid balance was adjusted for length of time interval and weight. 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. |
Day 1 up to Day 7
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SOFA Score
大体时间：Day 1 up to Day 7, Day 14 and Day 29
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The SOFA score, is used to track a patient's status during the stay in an intensive care unit. This scoring system is used to determine the extent of a person's organ function or rate of failure. The scoring system comprise of scores for six different system: Respiratory System; Nervous System; Cardiovascular System; Liver; Coagulation; and Renal System. Score for each system ranges from 0-4 (0=normal, 4=worst). Total SOFA score is a sum of the individual system score and range from 0 to 24, 0 being the better and 24 being the worst patient status. 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. |
Day 1 up to Day 7, Day 14 and Day 29
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Pulmonary Function : Change From Baseline in PaO2/FiO2
大体时间：Day 1 up to Day 7
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Change from Baseline in PaO2/FiO2 was observed at each time-point. 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. |
Day 1 up to Day 7
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Pulmonary Function : Change From Baseline in Tidal Volume
大体时间：Day 1 up to Day 7
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Change from Baseline in tidal volume was observed at each time-point. 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. |
Day 1 up to Day 7
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Change From Baseline in Arterial Blood Gas (Lactate)
大体时间：Day 1 up to Day 7
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Change from Baseline in arterial blood gas (lactate) was observed at each time-point. 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. |
Day 1 up to Day 7
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Days Alive and Free of Any Organ Dysfunction at Day 7
大体时间：At Day 7
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Percentage of days alive and free of any organ dysfunction (i.e. no. of days divided by 7). 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. |
At Day 7
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Percentage of Patients Alive and Free of All Vasopressors
大体时间：At Day 7, Day 14 and Day 28
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Percentage of patients alive and free of all vasopressors was assessed on Days 7, 14, and 28. 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. |
At Day 7, Day 14 and Day 28
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Percentage of Days Alive and Free of Dialysis
大体时间：At Day 7, Day 14 and Day 28
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Percentage of days alive and free of dialysis was assessed on Days 7, 14, and 28. 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. |
At Day 7, Day 14 and Day 28
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Percentage of Days Alive and Free of Ventilation
大体时间：At Day 7
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Percentage of days alive and free of ventilation was assessed on Days 7, 14, and 28. 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. |
At Day 7
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Mortality
大体时间：At Day 1, 7, 14, and 28
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Mortality was assessed as percentage of patients dead at pre-specified time points. 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. |
At Day 1, 7, 14, and 28
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Incidence of Abnormal Changes in ECG
大体时间：Day 1 up to Day 7
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The number of patients having abnormal changes in ECG variables during the trial period was presented. 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. |
Day 1 up to Day 7
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合作者和调查者
出版物和有用的链接
一般刊物
- Russell JA, Vincent JL, Kjolbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care. 2017 Aug 15;21(1):213. doi: 10.1186/s13054-017-1798-7.
- Rehberg S, Yamamoto Y, Sousse L, Bartha E, Jonkam C, Hasselbach AK, Traber LD, Cox RA, Westphal M, Enkhbaatar P, Traber DL. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1245-54. doi: 10.1152/ajpheart.00390.2012. Epub 2012 Sep 7.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
FE 202158 1.25的临床试验
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Changchun Intellicrown Pharmaceutical Co. LTD招聘中
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Sichuan Enray Pharmaceutical Sciences Company招聘中宫颈癌 | 乳腺癌 | 大肠癌 | 卵巢癌 | 肺癌 | 晚期实体瘤 | 胰腺癌 | 甲状腺癌 | 外阴癌中国
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Fondation Ophtalmologique Adolphe de Rothschild招聘中