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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Cirrhosis With Septic Shock

Intervention / Treatment
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* Drug: Terlipressin
* Drug: Noradrenaline


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Noradrenaline<br>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<br>* 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<br>|
| Experimental: Terlipressin<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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. |