| 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
|
|
|
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
|
|
|
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. |