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

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ClinicalTrials.gov Identifier: NCT03822091
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research

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.

Condition or disease Intervention/treatment Phase
Type 1 HEPATO RENAL SYNDROME(HRS) Drug: Terlipressin Drug: Terlipressin and Noradrenaline Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of The Effectiveness of Terlipressin Infusion Alone Vs Terlipressin With Noradrenaline Infusion In The Treatment of Hepatorenal Syndrome Type 1
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: TERLIPRESSIN GROUP Drug: Terlipressin

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 :

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

Experimental: TERLIPRESSIN WITH NORADRENALINE GROUP Drug: Terlipressin and Noradrenaline

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 Outcome Measures :
  1. Number of patients responding to treatment. [ Time Frame: 15 days ]
    Complete response defined as serum creatinine <1.5 mg/dl


Secondary Outcome Measures :
  1. Number of patients who will develop adverse events due to drugs used for treatment [ Time Frame: 15 days ]
  2. Number of patients surviving without transplant. [ Time Frame: 90 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03822091


Contacts
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Contact: Virendra Singh, DM 7087009338 virendrasingh100@hotmail.com
Contact: Akshaya Jayachandran, MBBS 8264694974 aks.251192@gmail.com

Locations
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India
Post Graduate Institute of Medical Education and Research Recruiting
Chandigarh, India, 160012
Contact: Virendra Singh, DM    7087009338    virendrasingh100@hotmail.com   
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research

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Responsible Party: Dr.Virendra Singh, Professor of Hepatology, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03822091     History of Changes
Other Study ID Numbers: TERLI AND NORAD IN HRS
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Syndrome
Hepatorenal Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Kidney Diseases
Urologic Diseases
Terlipressin
Norepinephrine
Antihypertensive Agents
Vasoconstrictor Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents