Terlipressin for HRS-AKI in Liver Transplant Candidates (INFUSE)

Exclusion Criteria

• •1. Serum creatinine level greater than 5.0 mg/dL. Subjects with value greater than 5.0 mg/dL may be enrolled with Sponsor prior approval.
• •2. MELD score ≥ 35
• •3. Acute on Chronic Liver Failure (ACLF) grade 3 (according to the CLIF Consortium grading system).
• •4. Uncontrolled sepsis and/or uncontrolled bacterial infection (e.g., persisting bacteremia, persisting ascitic fluid leukocytosis, fever, increasing leukocytosis with vasomotor instability).
• •5. Shock.
• •6. Current or recent (within 4 weeks) treatment with or exposure to nephrotoxic agents: eg, aminoglycosides, amphotericin, cyclosporine A, cisplatin, nonsteroidal anti-inflammatory drugs (NSAIDs: e.g., ibuprofen, naproxen, diclofenac), significant exposure to radiographic contrast agents (large doses or multiple injections of iodinated contrast media; e.g., during coronary or abdominal angiogram).
• •7. Estimated life expectancy of less than 7 days.
• •8. Advanced Hepatocellular Carcinoma ( HCC) with expected survival of \< 6 months
• •9. Superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins (e.g., Amanita toxin with mushroom poisoning carbon tetrachloride), with the exception of acute alcoholic hepatitis.
• •10. Evidence of obstructive uropathy or parenchymal renal disease. Renal ultrasound or other imaging not required but should be taken if suspicious.
• •11. Tubular epithelial casts, heme granular casts (range of 1-3 granular casts acceptable), hematuria or microhematuria on urinalysis that is indicative of acute tubular necrosis and/or intrinsic renal disease.
• •12. Subjects known to be pregnant; all women of child-bearing age and potential must have a negative pregnancy test.
• •13. Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary edema, congestive heart failure, or persisting symptomatic peripheral vascular disease, myocardial infarction or stable chronic angina within the past 12 months, or any other cardiovascular disease judged by the investigator to be severe and creates a risk to subject with concurrent terlipressin use.
• •14. Current or recent (within 4 weeks) renal replacement therapy (RRT) or anticipation of RRT within 3 days on enrollment.
• •15. Participation in other clinical research involving investigational medicinal products within 30 days of starting study drug that would adversely affect participation in this or the current trial.
• •16. Transjugular intrahepatic portosystemic shunt (TIPS) within 30 days of starting study drug.
• •17. For the Prospective Group: All vasopressors must be stopped prior to treatment with terlipressin. Use of vasopressors (e.g., norepinephrine, epinephrine or vasopressin dopamine or other vasopressors) of ≥ 3 consecutive days within the prior 14-day screening period are excluded. Patients receiving a vasopressor other than midodrine within 24 hours of qualifying SCr are excluded, i.e, a 24-h washout is required prior to enrollment.
• •Note: Patients receiving midodrine and octreotide may be enrolled. Midodrine and octreotide treatment must be stopped prior to enrollment.
• •18. Known allergy or sensitivity to terlipressin.