Terlipressin in Septic Shock in Cirrhosis

Effects on Survival of Terlipressin Administration in Cirrhotic Patients With Severe Sepsis or Septic Shock. A Randomized, Open Labelled Controlled Trial

Septic shock is a frequent and severe complication in cirrhosis. Current mortality rate ranges between 50 and 80% of cases. Refractory shock, hepatorenal failure and variceal bleeding are the main causes of death of these patients. Terlipressin administration could prevent these complications and improve survival in this setting.

Aim: To evaluate the effects of terlipressin administration on hospital survival in cirrhotic patients with severe sepsis or septic shock.

Methods: Prospective, open labelled, controlled trial evaluating 72 cirrhotic patients with severe sepsis or septic shock who will be randomized to receive terlipressin plus alpha-adrenergic drugs or only alpha-adrenergic drugs at shock diagnosis. Patients will be submitted to continuous systemic hemodynamic monitoring (S. Ganz catheter or Vigileo). Changes in vasoactive systems and cytokines levels will be also evaluated.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Septic Shock
• Intervention / Treatment: Drug: Terlipressin; Drug: alpha adrenergic drugs

Detailed Description

Prospective, open labelled, RCT evaluating 72 cirrhotic patients with severe sepsis or septic shock (36 per arm) who were randomized to receive terlipressin plus alpha-adrenergic drugs or alpha-adrenergic drugs in the first 24h after septic shock diagnosis. Impact of terlipressin administration on shock reversal, changes in vasoactive systems, inflammatory response, incidence of variceal bleeding and type-1 HRS and ICU and hospital mortality was investigated

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18 and 80 years;
2. Diagnosis of cirrhosis based on histology or on clinical, laboratory and ultrasonographical data;
3. Diagnosis of septic shock based on the presence of data compatible with systemic inflammatory response syndrome, a mean arterial pressure below 60 mmHg during more than 1 hour despite adequate fluid resuscitation, and need for circulatory support with vasopressor drugs.

Exclusion Criteria:

1. More than 24 hours of evolution of the shock;
2. Cardiac index < 2,5 l/min;
3. History of HIV infection or clinically relevant pulmonary, renal or cardiac disease except for atrial fibrillation;
4. Pregnancy;
5. Advanced hepatocellular carcinoma (Milan criteria);
6. Previous history of transplantation;
7. Uncontrolled gastrointestinal bleeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Terlipressin group; Terlipressin in continuous infusion plus alpha adrenergic drugs (noradrenaline and/or dopamine in continuous infusion)	Drug: Terlipressin; Terlipressin 2-12 mg/24h intravenously in continuous infusion. Duration: until 24h after shock resolution.; Other Names: Glypressin
Active Comparator: Control group; Alpha adrenergic drugs (noradrenaline and/or dopamine in continuous infusion)	Drug: alpha adrenergic drugs; Dopamine (1-20 µg/Kg/min) and/or norepinephrine (0.05-4 µg/Kg/min) until shock resolution; Other Names: Dopamine and/or norepinephrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hospital survival	Hospitalization

Secondary Outcome Measures

Outcome Measure	Time Frame
Refractory shock	ICU admission
Variceal bleeding	ICU admission
Hepatorenal syndrome	Hospitalization

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Investigators: Principal Investigator: Javier Fernandez, MD, Hospital Clinic of Barcelona; Study Director: Vicente Arroyo, MD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 22, 2008
• First Submitted That Met QC Criteria: March 3, 2008
• First Posted (Estimate): March 4, 2008

Study Record Updates

• Last Update Posted (Estimate): February 24, 2016
• Last Update Submitted That Met QC Criteria: February 23, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Survival; Septic shock; Cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Liver Diseases; Sepsis; Fibrosis; Shock, Septic; Shock; Liver Cirrhosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine; Dopamine; Terlipressin; Adrenergic Agents
• Other Study ID Numbers: 05-SS-JFDEZ-1; EUDRACAT-2005-000439-56; 2005-000439-56 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are currently writing the manuscript