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NCT Number: NCT03822091

Terlipressin Infusion Alone Vs Terlipressin With Noradrenaline Infusion In The Treatment of Hepatorenal Syndrome Type 1

Hepatorenal syndrome (HRS) is defined as a functional renal failure in a patient with chronic liver disease, or liver cirrhosis.The splanchnic circulation undergoes severe vasodilation, as a result of portal hypertension, causing an underfilling of systemic arteries.This results in intense renal vasoconstriction and functional renal failure. The best treatment options for HRS I would be a drug which has renal vasodilator property and additional splanchnic vasoconstriction. An increase in circulating blood volume would be of additional benefit. Currently Terlipressin is considered superior to other drugs in the management of HRS I. Other drugs in use are Noradrenaline and Midodrine. Albumin is added to these drugs in order to expand plasma volume. Terlipressin, a Vasopressin analog, has agonistic activity at V1 receptors. Noradrenaline acts as an agonist at α-adrenergic receptors with mild β-agonistic activity. The two major drugs used in the management of HRS act at different receptors and have completely varied mechanisms of action. Thus, a combination therapy would improve the rate of response considerably. There have been multiple studies, measuring the efficacy, safety and dosing of both drugs, but none combining both Terlipressin and Noradrenaline. Hence our study would be a pioneer in formulating a new and possibly more efficacious treatment protocol for patients of Type I HRS, in whom the treatment options are otherwise very limited. If successful, this would open new horizons of therapy for Terlipressin refractory HRS, which, otherwise is an ominous condition.

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Key information

Conditions

Type 1 HEPATO RENAL SYNDROME(HRS)

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

age>18 years and <80 yrs;
Cirrhosis as diagnosed by clinical findings, endoscopy or USG examination or by liver biopsy.
HRS I as defined by the following features:

The patient should have Cirrhosis and also ascites
Renal failure of rapid onset -Initial value of sCr, doubling to reach a level of more than 226mmol/L (2.5 mg/dL) in less than two weeks
There should be absence of shock.
sCr value does not reduce to less than 1.5 mg/dl even after 2 days of stopping diuretics and giving Inj.Albumin for plasma volume expansion (1g/kg ) upto 100g/day.
No H/O being treated currently or recently with drugs having nephrotoxicity.
Absence of parenchymal renal disease:

Proteinuria < 0.5g/day
Absence of microhaematuria (<50 red cells/high powered field)
Normal renal ultrasonography

Exclusion criteria

AKI improved after plasma volume expansion
Any history of coronary artery disease, peripheral vascular disease, arrhythmias, and cardiomyopathy.
Hepatocellular Carcinoma
Septic shock
Any severe extra-hepatic condition including respiratory and cardiac failure.
Any contraindication which precludes the use of Noradrenaline and Terlipressin

Treatment and study plan

Terlipressin

Drug

Patients with Type 1 HRS will be given Terlipressin at the dose of 2mg/24 hrs as infusion. After 48 hours of initial monitoring, patients who do not respond to the initial dose of Terlipressin, and randomised into group A and B. Group A patients will receive further higher doses of Terlipressin. The dose of Terlipressin will be increased by 1mg after 24 hrs if:

the creatinine values decrease by <12.5%
MAP increase of <10 mmHg
urine output of <200 ml in 4 hours.

Maximum terlipressin dose will be given upto 12 mg/day.Albumin will be administered in both arms according to standard protocol at the following dose :

1st day - Albumin at 1 gram/kg - a maximum dose of 100grams can be given.
A dose of 20gram/day to 60gram/day in the following days.

Terlipressin and Noradrenaline

Drug

Patients with Type 1 HRS will be given Terlipressin at the dose of 2mg/24 hrs as infusion. After 48 hours of initial monitoring, patients who do not respond to the initial dose of Terlipressin, will be randomised into group A and B. Group B patients will be treated with

Terlipressin(2mg/24hr infusion- fixed dose) and Noradrenaline, which would be given as a continuous infusion at a starting dose of 0.5 mg/hr. The dose od noradrenaline will be increased every 24 hours in steps of 0.5 mg/hr, the maximum dose being 3 mg/hr IF:

the creatinine values decrease by <12.5%
MAP increase of <10 mmHg
urine output of <200 ml in 4 hours.

Primary outcomes

Number of patients responding to treatment.

Time frame: 15 days

Complete response defined as serum creatinine <1.5 mg/dl

Secondary outcomes

Number of patients who will develop adverse events due to drugs used for treatment

Time frame: 15 days
Number of patients surviving without transplant.

Time frame: 90 days

Sponsors and collaborators

Lead sponsor

Post Graduate Institute of Medical Education and Research, Chandigarh

Other

Registry information

Official study title

Comparison of The Effectiveness of Terlipressin Infusion Alone Vs Terlipressin With Noradrenaline Infusion In The Treatment of Hepatorenal Syndrome Type 1

Important dates

Study start: 2019
Primary completion: 2020
Study completion: 2020
First posted: Jan 30, 2019
Registry last updated: May 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.