Efficacy and Safety of Monotherapy With Noradrenaline and Terlipressin in Patients of Cirrhosis With Septic Shock Admitted to Intensive Care Unit

A Prospective Open Label Randomized Non Inferiority Trial to Compare the Efficacy and Safety of Monotherapy With Noradrenaline and Terlipressin in Patients of Cirrhosis With Septic Shock Admitted to Intensive Care Unit.

The Patient evaluated in Emergency room since admission and detailed history and clinical examination done .The in hospital cases where sepsis is the culprit and shifted to Intensive Care Unit (ICU) in view of septic shock were included since onset of shock.

Initial fluid resuscitation done and if the patient were no fluid responsive they were randomized into arms noradrenaline or terlipressin and the dose escalated to achieve the primary objectives. At the same time the strict vitals monitoring and standard medical therapy for sepsis including antibiotics and other supportive therapy continued. The patients were followed up till discharge, death or up to 28days after enrollment into the protocol (whichever the longest). The detail methodology has been explained in column 14 later.

Study Overview

• Status: Completed
• Conditions: Cirrhosis With Septic Shock
• Intervention / Treatment: Drug: Noradrenaline; Drug: Terlipressin

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient of cirrhosis or ACLF (Acute on Chronic Liver Failure) with septic shock (defined later).
• Age 18-70yrs
• An informed consent from the patient or relative

Exclusion Criteria:

• Pronounced cardiac dysfunction( valvular heart disease, coronary artery disease),
• Acute mesenteric ischemia (confirmed or suspected) or vasospastic diathesis (e.g. Reynaud's syndrome or related diseases).
• Pregnancy
• Previous history of transplantation on immunosuppressant.
• Acute gastrointestinal bleed.(defined later)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Noradrenaline; Noradrenaline: Noradrenaline 2amp (4000mcg in 50ml) at 6ml/hr = 7.5mcg/min and dose maximum 60mcg/min 24ml/hr double strength. The dose to be increased every 15min from start dose by 1ml and to decrease by 0.5ml every 15min keeping MAP (Mean Arterial Pressure)>65.	Drug: Noradrenaline; Noradrenaline 2amp (4000mcg in 50ml) at 6ml/hr = 7.5mcg/min and dose maximum 60mcg/min 24ml/hr double strength. The dose to be increased every 15min from start dose by 1ml and to decrease by 0.5ml every 15min keeping MAP (Mean Arterial Pressure)>65
Experimental: Terlipressin; Terlipressin (1.3mcg/min i.e 2mg over 24 hr to max of terlipressin 5.2mcg/min i.e. up to 8mg over 24hr) .The dose to be increased every 15min from start dose by 1ml and to decrease by 0.5ml every 15min keeping MAP (Mean Arterial Pressure)>65 .Terlipressin 2mg in 48ml,1ml=42mcg=0.67mg/min, max dose 8mg/day- 8ml/hr of infusion.	Drug: Terlipressin; Terlipressin (1.3mcg/min i.e 2mg over 24 hr to max of terlipressin 5.2mcg/min i.e. up to 8mg over 24hr) .The dose to be increased every 15min from start dose by 1ml and to decrease by 0.5ml every 15min keeping MAP (Mean Arterial Pressure) >65 .Terlipressin 2mg in 48ml,1ml=42mcg=0.67mg/min, max dose 8mg/day- 8ml/hr of infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Hemodynamic improvement as defined as mean arterial pressure > 65 mmHg.	48 hrs

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	Day 3, Day 7 and Day 28
Number of organ system involved as defined by SOFA (Sequential Organ Failure Assessment)	Within 28 days
Days free of vasopressors	Within 28 days
Days free of ventilatory support	Within 28 days
Days free of steroid	Within 28 dyas
Length of stay	Within 28 days
Incidence of serious adverse events.	Within 28 days.

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Publications and helpful links

General Publications

• Choudhury A, Kedarisetty CK, Vashishtha C, Saini D, Kumar S, Maiwall R, Sharma MK, Bhadoria AS, Kumar G, Joshi YK, Sarin SK. A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock. Liver Int. 2017 Apr;37(4):552-561. doi: 10.1111/liv.13252. Epub 2016 Oct 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: April 2, 2013
• First Submitted That Met QC Criteria: April 11, 2013
• First Posted (Estimate): April 19, 2013

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: December 1, 2013

More Information

Terms related to this study

• 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; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine; Terlipressin
• Other Study ID Numbers: ILBS-Sepsis-01