Efficacy and Safety of Vasopressin Versus Terlipressin as a Second Vasopressor in Critically Ill Cirrhotics With Septic Shock- the VITEL-C Trial

NCT05315557 | Unknown

• 1 other identifier: ILBS-Cirrhosis-48
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response. A Subset of sepsis is septic shock which has almost 4-6 times the mortality when compared to sepsis. Septic shock has underlying cellular and metabolic abnormalities in addition to circulatory dysfunction. The circulatory dysfunction in sepsis is in the form of severe vasodilatation with high cardiac index. Cirrhosis is a state of hyperdynamic circulation. The mortality of septic shock in these group of patients is still higher. At the onset of septic shock there is initially an increased secretion of Arginine vasopressin. However, this initial rise is short lasting, and the vasopressin levels come back to normal or low serum levels with continued hypotension. However, even normal levels are too low for the degree of hypotension in septic shock. This causes a relative deficiency of vasopressin in septic shock. The exact time when this fall happens is not known and it is likely to be variable. Vasopressin was therefore tried as an agent in septic shock. Terlipressin is a synthetic analogue of vasopressin. It has a greater selectivity for the V1 receptor. Terlipressin is also shown to be effective in septic shock in cirrhotics3. Other vasoactive agents are not preferred in cirrhotics - dopamine due to high risk of arrhythmias and dobutamine as baseline cardiac output of cirrhotics is high which further increases in sepsis and dobutamine would further add to it. However, it may be given in myocardial dysfunction. Noradrenaline is recommended as the first vasopressor to be started in general in septic shock population. No study has compared the effectiveness of vasopressin and Terlipressin when added to noradrenaline in patients with cirrhosis. Acute kidney injury is a very common complication of septic shock in cirrhotics.

Conditions

Septic Shock; Cirrhosis, Liver

Outcome Measures

Primary Outcomes (1)

• Improvement in systemic hemodynamics at 6 hours after randomization

  Improvement in systemic hemodynamics defined as discontinuation of noradrenaline infusion OR reversal of shock

  6 hours after randomization

Secondary Outcomes (30)

• Reduction in dose of noradrenaline at the end of 6 hours

  6 hours

• Amount of noradrenaline requirements between in each arm at the end of 6 hours

  6 hours

• Improvement in Systemic Vascular Resistance (SVR) by 10% or above 500 at 6 hours

  6 hours

• Improvement in SVR by 10% or above 500 at 12 hours

  12 hours

• Improvement in SVR by 10% or above 500 at 48 hours

  48 hours

Study Arms (2)

Terlipressin

EXPERIMENTAL

Terlipressin 1mg/24 hours

Drug: Terlipressin

Vasopressin

ACTIVE COMPARATOR

Vasopressin 0.03 U/hour

Drug: vasopressin

Interventions

Terlipressin DRUG

1mg/24 hour and titrate according to MAP

Terlipressin

vasopressin DRUG

0.03 U/hour and titrate according to MAP

Vasopressin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70yrs
• An informed consent from the patient or relative

You may not qualify if:

• Age \<18 years and \> 70 years
• Stroke
• Severe sepsis requiring higher dose of noradrenaline (\>1mcg/Kg/min)
• Myocardial dysfunction, Coronary artery disease, Arrhythmias
• Peripheral Vascular disease
• Gut Paralysis
• Acute on chronic liver failure (ACLF)
• Hepato-cellular carcinoma (HCC), intrahepatic or extrahepatic malignancy
• Complete portal vein thrombosis
• Hepatic vein outflow tract obstruction (HVOTO)
• Pregnancy
• Patients with Pa02/FiO2 ratio \<150
• CKD
• COPD
• Severe coagulopathy - platelets \<20,000 and INR \> 4

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Shock, Septic; Liver Cirrhosis

Interventions

Terlipressin; Vasopressins

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Liver Diseases; Digestive System Diseases; Fibrosis

Intervention Hierarchy (Ancestors)

Lypressin; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Dr Vishnu Girish, MD

CONTACT

01146300000; vishnugirish@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: April 7, 2022
• Study Start: April 5, 2022
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: April 7, 2022

Record last verified: 2022-03

Locations

IN (1)