Safety and Efficacy of Continuous Infusion of Terlipressin With Norepinephrine Versus Norepinephrine Alone in Improving Outcomes of Acute Kidney Injury in Acute on Chronic Liver Failure With Septic Shock

NCT06556472 | Not Yet Recruiting

• 1 other identifier: ILBS-ACLF-19
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

ACLF is defined differently in APASL,EASL and AASLD.APASL talks of reversibility in ACLF as per its definition and constitution of Homogenous population with ACLF.The definition of ACLF as per APASL is an acute hepatic insult manifesting as jaundice (serum bilirubin ≥ 5 mg/dL (85 micromol/L) and coagulopathy (INR ≥ 1.5 or prothrombin activity \< 40%) complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis, and is associated with a high 28-day mortality. 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. Currently, Norepinephrine is recommended as the first vasopressor to be started in general in septic shock population.(3) Catecholamines are the clinically used vasopressor agents of choice for supporting arterial blood pressure and ensuring adequate organ perfusion. Development of adrenergic hyposensitivity with loss of catecholamine presser effects is seen in advanced stages of Vasodilatory Shock. Progressively increasing catecholamine therapy frequently enters into a vicious cycle of major adverse side effects resulting in continuous clinical deterioration necessitating further catecholamine excess.

Conditions

Acute on Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• Proportion of patients developing 1 stage improvement in Acute kidney injury stage with resolution of shock at day 4 in both groups

  Day 4

Secondary Outcomes (5)

• Outcome of acute kidney injury at day 4,7

  Day 4 and 7

• Incidence of adverse events in both groups

  1 year

• Need of renal replacement therapy at day 7

  Day 7

• Duration of ICU and hospital stay

  1 year

• Mortality

  Day 7 and 28

Study Arms (2)

Continuous terlipressin infusion + Norepinephrine

EXPERIMENTAL

1. Patients in this group will receive continuous terlipressin infusion (1 mg/24 hr on day 1, increasing to 1 mg in 24 hours if target MAP not achieved ,reaching maximum terlipressin dose of 4 mg/24 hr on day 4).If target MAP not achieved by terlipressin dose ,increase noradrenaline dose keeping terlipressin maximum 1 mg ,2 mg ,3mg ,4mg at Day 1,2,3,4 respectively. 2. Norepinephrine will be initiated @0.05mcg/kg/min and titrated upto 0.5 mcg/kg/min to maintain a MAP \> 65 to 75 mm Hg. 3. IV albumin as per volume status to maintain target MAP . 4. If the target MAP is not achieved, a third vasopressor along with hydrocortisone, Adrenaline and then phenylephrine.

Drug: Terlipressin; Drug: Norephrine

Norepinephrine

ACTIVE COMPARATOR

1. Patients in this group will receive norepinephrine only, with a dose range of 0.05 mcg/kg/min to 0.5 mcg/kg/min to maintain a MAP \> 65 to 75 mm Hg. 2. IV albumin as per volume status to maintain target MAP . 3. If the target MAP is not achieved, vasopressin along with hydrocortisone, followed by adrenaline and phenylephrine, may be added as a fourth vasopressor.

Drug: Norephrine

Interventions

Terlipressin DRUG

1\. Patients in this group will receive continuous terlipressin infusion (1 mg/24 hr on day 1, increasing to 1 mg in 24 hours if target MAP not achieved ,reaching maximum terlipressin dose of 4 mg/24 hr on day 4).If target MAP not achieved by terlipressin dose ,increase noradrenaline dose keeping terlipressin maximum 1 mg ,2 mg ,3mg ,4mg at Day 1,2,3,4 respectively.

Continuous terlipressin infusion + Norepinephrine

Norephrine DRUG

1\. Patients in this group will receive norepinephrine only, with a dose range of 0.05 mcg/kg/min to 0.5 mcg/kg/min to maintain a MAP \> 65 to 75 mm Hg.

Continuous terlipressin infusion + Norepinephrine; Norepinephrine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age\>18 years and \<60 yrs
• ACLF as per APASL
• AKI according to KDIGO Criteria
• septic shock requiring norepinephrine (\<0.05mcg/kg/min).

You may not qualify if:

• Septic shock requiring 2 vasopressors (Norephinephrine reuirement \> 0.05mcg/kg/min)
• Symptomatic cardiopulmonary disease
• Chronic kidney disease
• Peripheral vascular disease
• Hepatocellular carcinoma outside Milan criteria
• Prior use of terlipressin in last 48 hours
• Patients with hypovolemic or hemorrhagic shock
• Patients already meeting criteria for dialysis or with history of dialysis in last 7 days
• Intrinsic kidney disease, Acute tubular necrosis with urinary output \< 400 ml /day or obstructive uropathy
• History of immunosuppressive drugs
• Pregnancy
• Human immunodeficiency virus 1 and 2
• Portal vein thrombus

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences (ILBS)

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

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Terlipressin; Nordefrin

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; 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; Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Dr Jitendra Kumar Singh, MD

CONTACT

01146300000; jitendra2602kc@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: July 30, 2024
• First Posted: August 16, 2024
• Study Start: August 15, 2024
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: August 16, 2024

Record last verified: 2024-07

Locations

IN (1)