A Multi Center, Double-Blind, Randomized, Controlled Study to Determine the Safety and Pharmacokinetics of Ifetroban Injection in Hepatorenal Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 64
- 试验地点
- 3
- 主要终点
- •To determine the pharmacokinetic profile of multiple daily intravenous doses of ifetroban and its major metabolite, ifetroban acylglucuronide.
研究概览
简要总结
This Phase 2a double-blind, multi-center, randomized, controlled study will evaluate the pharmacokinetics, safety and tolerability of ifetroban administered as daily IV doses in recently diagnosed HRS patients. Patients will be stratified based upon Type 1 or Type 2 HRS diagnosis. Cohorts of eight HRS patients (per HRS type) will be assigned sequentially to escalating daily dose levels of ifetroban or vehicle (3:1) for assessment of pharmacokinetics. Escalation to the next dose level will be contingent upon the safety and tolerability of the preceding dose level as determined by a DSMB. If all regimens are studied, a total of 64 patients will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- Male
入选标准
- •Note- There is no upper limit specified in the protocol.
- •Inclusion Criteria
- •Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary).
- •Subjects with either Type 1 or Type 2 renal dysfunction defined as follows: a) Type 1: i) At least a doubling of the initial serum creatinine to >220 μmol/L (2.5 mg/dL), occurring over a period of less than 2 weeks.
- •OR ii) A 50% or greater reduction in the initial 24-hour creatinine clearance to <20 mL/min occurring over a period of less than 2 weeks.
- •b) Type 2: defined as at least a 33% reduction in creatinine clearance occurring over a period of greater than 2 weeks, with a serum creatinine >133μmol/L (1.5 mg/dL).
- •Oliguria occurring within 48 hours prior to 1st administration CTM.
- •Oliguria is defined as either of the following: a.
- •In the absence of CVP monitoring, oliguria that is not corrected by a fluid challenge of at least 20mL/kg isotonic crystalloid or comparable volume of colloid.
排除标准
- •History of allergy or hypersensitivity to ifetroban
- •Pregnant or nursing
- •Less than 18 years of age
- •SCr > 5.0 mg/dL
- •Platelet count at screening of <30 x 103 per μL
- •Active gastrointestinal hemorrhage
- •Evidence of obstructive or parenchymal renal disease (e.g., acute tubular necrosis, glomerular diseases, interstitial nephritis, and urinary obstruction, or lab results indicating proteinuria >500 mg/day, microhematuria [>50 RBCs/high power field], and/or abnormal renal ultrasound scanning).
- •Current or recent (within the preceding 5 days) treatment with any of the following drugs: aminoglycosides, acyclovir, cisplatin, methotrexate, cyclosporine, amphotericin B.
- •Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG.
- •NYHA class 3 or 4 heart failure.
- •Presence of hepatocellular carcinoma not transplantable by Milan criteria
- •Cardiopulmonary arrest without full recovery of mental status
- •Moribund and death expected within five days
- •Uncontrolled bacterial or fungal infections, defined as receiving appropriate antimicrobial therapy for >24 hours
- •Burns >30% body surface area
- •Exposed to investigational drugs within 30 days before 1st CTM administration.
- •(Subjects must be willing to provide written informed consent or consent of legally recognized representative, as evidenced by signature on an informed consent document approved by an Institutional Review Board [IRB], and agree to abide by the study restrictions if the subject is incapacitated, informed consent will be sought from a legally recognized representative).
- •Refusal to provide written authorization for use and disclosure of protected health information.
- •Be otherwise unsuitable for the study, in the opinion of the Investigator.
结局指标
主要结局
•To determine the pharmacokinetic profile of multiple daily intravenous doses of ifetroban and its major metabolite, ifetroban acylglucuronide.
时间窗: During the 72-hour Treatment Period, at Hour 168 and at day 28. | Adverse events will be monitored throughout the Post-treatment Period.
•To determine the tolerability and safety of ifetroban injection in patients with HRS.
时间窗: During the 72-hour Treatment Period, at Hour 168 and at day 28. | Adverse events will be monitored throughout the Post-treatment Period.
次要结局
- To determine if ifetroban changes renal function, showing evidence of HRS reversal.(During the 72-hour Treatment Period and at Hour 168)