A Multi-Center, Double-Blind, Randomized, Controlled Study to Determine the Safety and Pharmacokinetics of Ifetroban Injection in Hepatorenal Syndrome
Trial status: Open for Enrollment
Why is this study being done?
Ifetroban sodium (ifetroban) is an investigational drug that has been studied previously in healthy volunteers and patients with cardiovascular diseases. Cumberland Pharmaceuticals Inc. (CPI) is developing ifetroban for treatment of type 1 and type 2 hepatorenal syndrome (HRS) and proposed to conduct a study in hospitalized adult patients with HRS to assess the safety and pharmacokinetics of escalating doses of ifetroban. The primary objective of this study is as follows:
- To determine the pharmacokinetic profile of multiple daily intravenous doses of ifetroban and its major metabolite ifetroban acylglucuronide.
- To determine the tolerability and safety of ifetroban injection in patients with HRS.
The secondary objective of this study is as follows:
• To determine if ifetroban changes renal function, showing evidence of HRS reversal.
Who is eligible to participate?
1. Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary).
2. Subjects with either Type 1 or Type 2 renal dysfunction defined as follows:
- 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 week, 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.
- 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).
3. Oliguria occurring within 48 hours prior to 1st administration CTM. Oliguria is defined as either of the following:
- An average urine output of < 35 mL/hr measured for at least 4 hours, occurring with a measured central venous pressure (CVP) > 12 mmHg, OR
- 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.
1. History of allergy or hypersensitivity to ifetroban
2. Pregnant or nursing
3. Less than 18 years of age
4. Serum creatinine (SCr) > 5.0 mg/dL
5. Platelet count at screening of < 30,000/ µL
6. Active gastrointestinal hemorrhage
7. 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).
8. Current or recent (within the preceding 5 days) treatment with any of the following drugs: aminoglycosides, acyclovir, cisplatin, methotrexate, cyclosporine, amphotericin B.
9. Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG.
10. New York Heart Association class 3 or 4 heart failure.
11. Presence of hepatocellular carcinoma not transplantable by Milan criteria
12. Cardiopulmonary arrest without full recovery of mental status
13. Moribund and death expected within five days
14. Uncontrolled bacterial or fungal infections, defined as receiving appropriate antimicrobial therapy for > 24 hours
15. Burns > 30% body surface area
16. Exposed to investigational drugs within 30 days before 1st CTM administration.
17. 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).
18. Refusal to provide written authorization for use and disclosure of protected health information.
19. Be otherwise unsuitable for the study, in the opinion of the Investigator.