Treatment of Type-1 Hepatorenal Syndrome Associated With Sepsis

NCT ID: NCT01932151

Last Updated: 2013-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

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.

Conditions

Hepatorenal Syndrome

Keywords

type-1 HRS; active bacterial infections; terlipressin and albumin; kidney function

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Terlipressin and albumin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

- Glypressyn, Ferring SA, Saint-Prex, Switzerland.; - Albúmina Humana Grífols, Grífols , Barcelona, Spain.

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Clinic of Barcelona

OTHER

Sponsor Role: lead

Responsible Party

Pere Gines

Chairman, Liver Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pere Ginès, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinc of Barcelona

Locations

Hospital Clinic de Barcelona

Barcelona, Barcelona, Spain

Countries

Spain

Other Identifiers

GIN-TER-2010-01

Identifier Type: -

Identifier Source: org_study_id