Terlipressin Infusion Alone Vs Terlipressin With Noradrenaline Infusion In The Treatment of Hepatorenal Syndrome Type 1
Condition: Type 1 HEPATO RENAL SYNDROME(HRS)
MeSH terms: Hepatorenal Syndrome; Syndrome
Study type: Interventional
Phase: Phase 3

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.
    


Intervention name(s): Terlipressin; Terlipressin and Noradrenaline
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Intervention MeSH terms: Terlipressin; Norepinephrine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment