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CTRI Number  CTRI/2013/02/003360 [Registered on: 07/02/2013] Trial Registered Prospectively
Last Modified On: 18/02/2014
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Role of L-Ornithine L-Aspartate in improving acute encephalopathy (altered sensorium) in patients with Liver Cirrhosis 
Scientific Title of Study   Efficacy of intravenous ‘L-ornithine L-aspartate’ in reversal of overt acute hepatic encephalopathy in patients with liver cirrhosis: a prospective, randomized, double-blind, placebo controlled trial 
Trial Acronym  HEAL (Hepatic Encephalopathy and LOLA) 
Secondary IDs if Any  
Secondary ID  Identifier 
HEAL-123  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Sandeep Singh Sidhu 
Designation  Professor 
Affiliation  D.M.C. and Hospital 
Address  Department of Gastroenterolgy D.M.C. and Hospital, Ludhiana
Department of Gastroenterolgy D.M.C. and Hospital, Ludhiana
Ludhiana
PUNJAB
141001
India 
Phone  9814025085  
Fax    
Email  dmcgastro@in.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Sandeep Singh Sidhu 
Designation  Professor 
Affiliation  D.M.C. and Hospital 
Address  Department of Gastroenterolgy D.M.C. and Hospital, Ludhiana
Department of Gastroenterolgy D.M.C. and Hospital, Ludhiana

PUNJAB
141001
India 
Phone  9814025085  
Fax    
Email  dmcgastro@in.com  
 
Details of Contact Person
Public Query
 
Name  Dr Sandeep Singh Sidhu 
Designation  Professor 
Affiliation  D.M.C. and Hospital 
Address  Department of Gastroenterolgy D.M.C. and Hospital, Ludhiana
Department of Gastroenterolgy D.M.C. and Hospital, Ludhiana

PUNJAB
141001
India 
Phone  9814025085  
Fax    
Email  dmcgastro@in.com  
 
Source of Monetary or Material Support  
Department of Gastroenterology, D.M.C. and Hospital, Ludhiana, Punjab 
 
Primary Sponsor  
Name  Department of Gastroenterology 
Address  D.M.C. and Hospital, Ludhiana 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sandeep Singh Sidhu  Department of Gastroenterology, D.M.C. and Hospital  Tagore Nagar, Ludhiana
Ludhiana
PUNJAB 
9814025085

dmcgastro@in.com 
Dr R K Dhiman  Department of Hepatology, Postgraduate Institute of Medical  Chandigarh 160012, India
Chandigarh
CHANDIGARH 
9914209337

rkpsdhiman@hotmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
DMC Hospital-Drug Trial Ethics Commitee  Approved 
PGIMER-Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Hepatic cirrhosis ,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  L-Ornithine L-Aspartate  L-Ornithine L-Aspartate, 30 grams per day as intravenous infusion over 24 hours 
Comparator Agent  Placebo  Placebo ampules as intravenous infusion over 24 hours 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  70.00 Year(s)
Gender  Both 
Details  a. Hepatic cirrhosis based on clinical, biochemical, radiological and/or histological data.
b. Patients with overt acute grade 2, 3 and 4 HE, according to the West Haven criteria.
c. Age of patient >18 years
d. Patients with or without a precipitating factor for the HE.
 
 
ExclusionCriteria 
Details  a. Patients who are terminally ill (End Stage Liver Disease, MELD more than 15)
b. Chronic HE, on Lactulose or antibiotics
c. Acute superposed liver injury (hepatitis) or acute on chronic liver failure
d. Severe septicemia with shock
e. Hepatocellular carcinoma
f. Wilson’s disease as the etiological factor of liver disease
g. Advanced cardiac or pulmonary disease
h. Acute renal failure or end stage renal disease
i. Neuro-degenerative disease or major psychiatric illness
j. Patients on sedatives or antidepressants
k. Pregnancy or breastfeeding
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
Mental state grade   5 days 
 
Secondary Outcome  
Outcome  TimePoints 
Blood ammonia levels

 
5 days 
Mortality  4 weeks 
Hospital stay  4 weeks 
 
Target Sample Size   Total Sample Size="164"
Sample Size from India="164" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 4 
Date of First Enrollment (India)   11/02/2013 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Hepatic encephalopathy (HE) is a potentially reversible functional disorder of the brain with neurological and psychiatric symptoms. HE occurs in up to 70% of patients with cirrhosis at some time during the course of disease. The chief neurotoxin implicated in the development of HE is ammonia. An important aim of treatment of HE is the reduction of the ammonia in the body by lowering the amount of ammonia produced and increasing its detoxification. Enteric production of ammonia can be decreased by non-absorbable disaccharides such as lactulose and antibiotics such as rifaximin. L-ornithine- L-aspartate (LOLA), the salt of the natural amino acids ornithine and aspartate acts through the mechanism of substrate activation to detoxify ammonia. In clinical trials, LOLA has shown a statistically significant effect with respect to reduction in HE grade, reduction of blood ammonia concentration and positive effects on psychomotor function in patients of cirrhosis with minimal HE and overt chronic Grade I HE, as compared to placebo. However, there is lack of data on the efficacy of LOLA in patients with overt acute hepatic encephalopathy which is one of the major causes of hospital admissions and resource utilization in decompensated cirrhotics. Each admission for HE causes a major financial loss to the family and financial burden on the society. Any drug which decreases the hospital stay by rapidly improving HE, will clearly lead to decreased hospital costs to the individual and the society as a whole. Hence, such a trial is a national priority. We hypothesize that LOLA, if added to the standard treatment of overt acute HE (i.e lactulose), may lead to a faster recovery and decrease in hospital stay of these patients.  In this prospective, randomized, placebo controlled trial, we aim to evaluate the efficacy of intravenous L-ornithine, L-aspartate in reversal of overt acute hepatic encephalopathy in patients with liver cirrhosis.

 
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