Hepatorenal Syndrome Type 1
Conditions
Brief summary
This is an open-label, multi-center study, investigating the efficacy and safety of terlipressin in Japanese patients with hepatorenal syndrome type 1.
Interventions
DRUGTerlipressin
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
\- Patients who were diagnosed with HRS type 1 according to the diagnostic criteria of HRS and whose serum creatinine value (SCr) doubled at 2.5 mg/dL or greater within 2 weeks or whose 24h creatinine clearance (Ccr) decreased by half at less than 20 mL/min. Patients should meet all the following 5 criteria: \[Modified International Ascites Club's Diagnostic criteria of HRS\] 1. Chronic or acute liver disease with advanced hepatic failure and portal hypertension. 2. Low glomerular filtration rate (SCr \>1.5 mg/dL or 24h Ccr \<40 mL/min) 3. Absence of shock, ongoing bacterial infection, current or recent (within 2 weeks) treatment with nephrotoxic drug 4. No sustained improvement in renal function (decrease in SCr to 1.5 mg/dL or less or increase in 24h Ccr to 40 mL/min or more) following diuretic withdrawal and expansion of plasma volume with 1,500 mL/24h of isotonic saline for 24 to 48h. 5. Protein urea \<500 mg/dL, and no ultrasonographic evidence of obstructive uropathy or parenchymal renal disease * Age; 20 to 79 years
Exclusion criteria
* Cr value ≥5 mg/dL * Child-Pugh Score ≥14 * Fulminant hepatitis * Septic shock * Hepatocellular carcinoma that does not meet the Milan Criteria * Acute renal failure caused by contrast medium * Chronic renal failure * Bradycardia (heart rate \<50/min) * Hyponatraemia (serum Na \<120 mEq/L) * Ischemic heart diseases (angina pectoris, myocardial infarction), heart failure or clinically relevant arrhythmia * Poor-controlled hypertension * Arteriosclerosis obliterans or peripheral vascular disorder * Cerebrovascular disorder * Respiratory diseases such as chronic obstructive pulmonary disease * Pregnant or possibly pregnant women and patients who or whose partner desire -pregnancy during the study period * Patients considered by the investigator or sub-investigator as unsuitable to participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in SCr value from baseline to end of treatment | 16 days |
Secondary
| Measure | Time frame |
|---|---|
| Laboratory test values | Up to 84 days |
| Vital signs | 16 days |
| ECG | Day 1,4,7,10,13,16 |
| The percentage of patients with Hepatorenal syndrome reversal (SCr value <=1.5 mg/dL) | 16 days |
| Incidence of adverse events and its severity | Up to 84 days |
| 24h Ccr, urine volume, urea nitrogen (BUN), urinary sodium excretions | 16 days |
| Mean arterial blood pressure, serum Na, serum K, plasma renin activity, aldosterone, norepinephrine, antidiuretic hormone (ADH), atrial natriuresis peptide (ANP) | 16 days |
| Overall survival | Up to 84 days |
| Pharmacokinetics - assessment of blood concentration | Blood PK sample collection: pre-dose, 5, 15, 30, 60, 90, 120, 150, 180, 240, and 360 minutes post-dose |
| The percentage of patients showing 20% or more reduction in SCr value from the baseline | 16 days |
Countries
Japan
Outcome results
None listed