Clinical trial NCT03822091: Terlipressin Infusion Alone Vs Terlipressin With Noradrenaline Infusion In The Treatment of Hepatorenal Syndrome Type 1
Official title: Comparison of The Effectiveness of Terlipressin Infusion Alone Vs Terlipressin With Noradrenaline Infusion In The Treatment of Hepatorenal Syndrome Type 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 HEPATO RENAL SYNDROME(HRS)
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2019-01-30
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

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

   1. The patient should have Cirrhosis and also ascites
   2. 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
   3. There should be absence of shock.
   4. 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.
   5. No H/O being treated currently or recently with drugs having nephrotoxicity.
   6. Absence of parenchymal renal disease:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Number of patients responding to treatment.
timeFrame: 15 days
Secondary outcomes:
measure: Number of patients who will develop adverse events due to drugs used for treatment
timeFrame: 15 days
measure: Number of patients surviving without transplant.
timeFrame: 90 days
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research
Study officials:
References: