Terlipressin in Septic Shock in Cirrhosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Liver Cirrhosis, Septic Shock

Intervention / Treatment
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* Drug: Terlipressin
* Drug: alpha adrenergic drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 80 years; Diagnosis of cirrhosis based on histology or on clinical, laboratory and ultrasonographical data; 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: More than 24 hours of evolution of the shock; Cardiac index < 2,5 l/min; History of HIV infection or clinically relevant pulmonary, renal or cardiac disease except for atrial fibrillation; Pregnancy; Advanced hepatocellular carcinoma (Milan criteria); Previous history of transplantation; Uncontrolled gastrointestinal bleeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital survival |  | Hospitalization | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock, Cirrhosis, Survival