Clinical trial NCT01373606: A Study of Terlipressin in Patients With Hepatorenal Syndrome Type 1
Official title: An Exploratory Study of FE999908 in Patients With Hepatorenal Syndrome Type 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatorenal Syndrome Type 1
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-06-15
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in SCr value from baseline to end of treatment
timeFrame: 16 days
Secondary outcomes:
measure: Incidence of adverse events and its severity
timeFrame: Up to 84 days
measure: Laboratory test values
timeFrame: Up to 84 days
measure: Vital signs
timeFrame: 16 days
measure: ECG
timeFrame: Day 1,4,7,10,13,16
measure: The percentage of patients with Hepatorenal syndrome reversal (SCr value <=1.5 mg/dL)
timeFrame: 16 days
measure: The percentage of patients showing 20% or more reduction in SCr value from the baseline
timeFrame: 16 days
measure: 24h Ccr, urine volume, urea nitrogen (BUN), urinary sodium excretions
timeFrame: 16 days
measure: Mean arterial blood pressure, serum Na, serum K, plasma renin activity, aldosterone, norepinephrine, antidiuretic hormone (ADH), atrial natriuresis peptide (ANP)
timeFrame: 16 days
measure: Overall survival
timeFrame: Up to 84 days
measure: Pharmacokinetics - assessment of blood concentration
timeFrame: Blood PK sample collection: pre-dose, 5, 15, 30, 60, 90, 120, 150, 180, 240, and 360 minutes post-dose
Other outcomes:
Locations:
city: Kansai
country: Japan
facility: Investigational site
city: Kanto
country: Japan
facility: Investigational site
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References:
citation: Narahara Y, Kanazawa H, Sakamoto C, Maruyama H, Yokosuka O, Mochida S, Uemura M, Fukui H, Sumino Y, Matsuzaki Y, Masaki N, Kokubu S, Okita K. The efficacy and safety of terlipressin and albumin in patients with type 1 hepatorenal syndrome: a multicenter, open-label, explorative study. J Gastroenterol. 2012 Mar;47(3):313-20. doi: 10.1007/s00535-011-0485-8. Epub 2011 Oct 25.