Treatment of Type-1 Hepatorenal Syndrome Associated With Sepsis

Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome Associated With Sepsis

Type 1 Hepatorenal syndrome (type-1 HRS) is a severe complication of patients with advanced cirrhosis characterized by marked renal failure and is associated with a very poor prognosis. Type-1 HRS is often precipitated by a bacterial infection, though it may occur spontaneously. It has been demonstrated that vasoconstrictor agents plus albumin are effective in the reversal of the renal failure. A large number of studies have shown that terlipressin improves renal function in patients with type 1 HRS; treatment is effective in 50-75% of patients approximately. Currently there are no specific studies about the treatment of type-1 HRS with ongoing infections.

Study Overview

• Status: Completed
• Conditions: Hepatorenal Syndrome
• Intervention / Treatment: Drug: Terlipressin and albumin

Detailed Description

All consecutive patients with cirrhosis hospitalized with an infection or who developed an infection during hospitalization for an acute decompensation of the disease in four university hospitals.

Criteria for inclusion were: 1/ cirrhosis as diagnosed by liver biopsy or a combination of clinical, biochemical, ultrasonographic, and/or endoscopic findings; 2/ age between 18 and 80 years; 3/ presence of sepsis, as defined by infection and signs of Systemic Inflammatory Response Syndrome; and 4/ occurrence of type-1 HRS during the infection, as defined by standard diagnostic criteria. Exclusion criteria were: 1/ hepatocellular carcinoma outside the Milan criteria; 2/ any severe extrahepatic condition, including cardiovascular, neurological, and organic kidney diseases; 3/ septic or hypovolemic shock; 4/ terminal condition (death expected in less than 48 hours); and 5/ lack of informed consent.

Aim: A proof of concept study to evaluate whether treatment with terlipressin and albumin in the course of an infection associated with type-1 HRS is effective and safe.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Cirrhosis as diagnosed by liver biopsy or a combination of clinical, biochemical, ultrasonographic, and/or endoscopic findings.
• Age between 18 and 85 years.
• Presence of sepsis, as defined by active infection, and signs of Systemic Inflammatory Response Syndrome.
• Occurrence of type-1 HRS during the infection, as defined by standard diagnostic criteria.

Exclusion criteria:

• Hepatocellular carcinoma outside the Milan criteria.
• Any severe extrahepatic condition, including cardiovascular, neurological, and organic kidney diseases.
• Septic or hypovolemic shock.
• Terminal condition (death expected in less than 48 hours).
• Lack of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Terlipressin and albumin; Single-group study (Type-1 Hepatorenal Syndrome Associated With Active Infections) Terlipressin was initially given at a dose of 1 mg/4h as an intravenous bolus for 2 days. If at day 3 serum creatinine had decreased at least 25% of the pretreatment values, the dose of terlipressin was not modified. In the remaining patients, the dose was increased up to a maximum of 2 mg/4h. Terlipressin was given until serum creatinine had decreased below 1.5 mg/dL (133 µmol/L) or for a maximum of 14 days.

Drug: Terlipressin and albumin; Single-group study (Type-1 Hepatorenal Syndrome Associated With Active Infections) Terlipressin was initially given at a dose of 1 mg/4h as an intravenous bolus for 2 days. If at day 3 serum creatinine had decreased at least 25% of the pretreatment values, the dose of terlipressin was not modified. In the remaining patients, the dose was increased up to a maximum of 2 mg/4h. Terlipressin was given until serum creatinine had decreased below 1.5 mg/dL (133 µmol/L) or for a maximum of 14 days. In addition to terlipressin, all patients received albumin at a dose of 1g per kg body weight during the first 24 hours, followed by 40g daily,targeted to obtain a central venous pressure (CVP) between 10 and 15 cm of water.; Other Names: - Glypressyn, Ferring SA, Saint-Prex, Switzerland.; - Albúmina Humana Grífols, Grífols , Barcelona, Spain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in serum creatinine values	baseline and 14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
changes in glomerular filtration rate	at 3 days and 14 days
Changes in arterial pressure	baseline to 14 days
changes in plasma renin activity	at 3 days and 14 days
changes in norepinephrine concentration	at 3 days and 14 days

Other Outcome Measures

Outcome Measure	Time Frame
Presence of adverse effects	14 days

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Investigators: Principal Investigator: Pere Ginès, MD, Hospital Clinc of Barcelona

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 14, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimate): August 30, 2013

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: kidney function; type-1 HRS; active bacterial infections; terlipressin and albumin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Liver Diseases; Syndrome; Hepatorenal Syndrome; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: GIN-TER-2010-01