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
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 12
- 主要终点
- Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
研究概览
简要总结
A study of ifetroban in the treatment of hepatorenal syndrome (HRS) in hospitalized adult patients to assess the safety and pharmacokinetics of 3 days of intravenous ifetroban.
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
- •Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary).
- •Subjects with either Type 1 or Type 2 HRS defined in a and b below:
- •a. Type 1: i. At least a doubling of the serum creatinine to a minimum of 220 µmol/L (2.5 mg/dL) at enrollment, occurring over a period of less than 14 days, OR ii. A 50% or greater reduction in the estimated glomerular filtration rate (GFR - calculated by the method of Cockcroft-Gault) to below 20 mL/min at enrollment occurring over a period of less than 14 days.
- •iii. A projected doubling of serum creatinine to a minimum of 2.5 mg/dL, expected to occur in less than 14 days based on the rate of change observed.
- •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 (SCr) > 133µmol/L (1.5 mg/dL).
- •Oliguria occurring within 48 hours prior to the first administration CTM. Oliguria is defined as an average urine output of < 35 mL/hr (measured for a minimum of 4 hours) under either of the following circumstances:
- •a. When measured central venous pressure (CVP) > 12 mmHg, OR b. following a fluid challenge consisting of either: i. at minimum 20 mL/kg isotonic fluid (e.g. any combination of 5% albumin, normal saline, blood or blood products) given over no more than 6 hours ii. at minimum 1 g/kg of hypertonic fluid (e.g. 25% albumin) given over no more than 24 hours iii. an equivalent combination of 3.b.i and 3.b.ii
排除标准
- •History of allergy or hypersensitivity to ifetroban
- •Pregnant or nursing
- •Less than 18 years of age
- •Serum creatinine at the time of enrollment greater than or equal to 5.0 mg/dL
- •Platelet count at screening less than 30 x 10^3 platelets/µL
- •Anticipated of planned need for dialysis within 5 days of first CTM dose.
- •Active gastrointestinal hemorrhage (where active is defined as evidence of bleeding within 48 hours of the first dose of CTM)
- •Evidence of current (within past 30 days) obstructive (post-renal) or intrinsic renal disease [including but not limited to: acute tubular necrosis (ATN), glomerular diseases/glomerulonephritis, acute interstitial nephritis (AIN), known urinary obstruction, proteinuria > 500 mg/day, microhematuria (> 50 RBCs/high power field), abnormal renal ultrasound, fractional excretion of sodium (FeNa) > 2.0%, any urinary casts other than hyaline.
- •Current or recent (within the preceding 5 days) treatment with nephrotoxic drugs including but not limited to: NSAIDs (prior 48 hours), angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), calcineurin inhibitors (cyclosporine, tacrolimus), aminoglycosides, amphotericin B, antiretrovirals and antivirals (adefovir, cidofovir, tenofovir, acyclovir, indinavir), cisplatin, methotrexate, cyclosporine, amphotericin B contrast agents, foscarnet, zoledronate, etc.
- •Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG.
- •New York Heart Association 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
- •Bacterial or fungal infections which have been unresponsive to at least 24 hours of appropriate antimicrobial therapy
- •Burns > 30% body surface area
- •Exposed to investigational drugs within 30 days before 1st CTM administration.
- •Inability to understand the requirements of the study. (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.
研究组 & 干预措施
5 mg ifetroban, Type 1
60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
干预措施: Ifetroban Injection (Drug)
Placebo, Type 1
60-minute intravenous infusion of 5% dextrose in sterile water given once daily for 3 days to subjects with Type 1 HRS.
干预措施: Placebo (Drug)
5 mg ifetroban, Type 2
60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
干预措施: Ifetroban Injection (Drug)
15 mg ifetroban, Type 1
60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
干预措施: Ifetroban Injection (Drug)
15 mg ifetroban, Type 2
60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.
干预措施: Ifetroban Injection (Drug)
50 mg ifetroban, Type 1
60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
干预措施: Ifetroban Injection (Drug)
50 mg ifetroban, Type 2
60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.
干预措施: Ifetroban Injection (Drug)
150 mg ifetroban, Type 2
60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.
干预措施: Ifetroban Injection (Drug)
Placebo, Type 2
60-minute intravenous infusion of 5% dextrose in sterile water given once daily for 3 days to subjects with Type 2 HRS.
干预措施: Placebo (Drug)
结局指标
主要结局
Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
时间窗: 3 days
Plasma concentrations of ifetroban and its primary active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
时间窗: 3 days
Plasma concentrations of ifetroban and it's major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide
时间窗: 3 days
Plasma concentrations of ifetroban and its major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
次要结局
- Safety: Day 28 Mortality(28 days)
- The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements(Day 0 to Day 5)
- Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL(Day 0 through Day 5)
- Change in 24-hour Urine Volume(Baseline to Hour 96)