A Trial for Comparing Rifaximin, Probiotic and L-ornithine- L Aspartate With Lactulose in Overt Hepatic Encephalopathy. (ARGO-HEC)

Qurratul Ain Jamil

Status and phase: Completed; Phase 4

Conditions: Overt Hepatic Encephalopathy

Treatments: Drug: Rifaximin plus lactulose; Drug: Lactulose; Drug: L-ornithine-L-aspartate plus latulose; Drug: Probiotic plus lactulose

Study type: Interventional

Funder types: Other

Identifiers

NCT07037394

187-2023-/PHEC

Details and patient eligibility

About

The goal of this trial is to learn if drugs in group A, B, C and D works to treat reversal of grades in people with overt hepatic encephalopathy. It will also provide information regarding safety of drugs in group A, B, C and D. The main question it aim to answer is:

Which study group is better in treating people of overt hepatic encephalopathy. Researchers will compare experimental group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) to control group A lactulose alone in the reversal of grades for people of hepatic encephalopathy.

Participants will:

Take drug from time of participation in the trial till the end of treatment (day 5) and grade reversal will be observed.

Full description

This clinical trial aim to compare the efficacy of four groups which are group A (lactulose) as controlled group, group B (rifaximin + lactulose), group C (probiotics + lactulose)and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) for treating overt hepatic encephalopathy.

Primary objective: The primary objective of our trial will be to compare the grade reversal in overt hepatic encephalopathy patients from the time of trial participation till the end of trial treatment (day 5) according to West Heaven Criteria in both control and interventional groups.

Secondary objectives:

1. To find the length of hospital stay and recovery time (in days) from hepatic encephalopathy in both control and interventional groups.
2. Monitoring of Adverse drug reactions in both control and interventional groups.
3. To assess the mortality in both control and interventional groups.

This trial is single-centered, parallel, multi-arm, 1:1:1:1 randomized, unblinded, lactulose controlled superiority clinical trial comparing the efficacy of four groups which are group A (lactulose) as controlled group, group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) for the treatment of overt hepatic encephalopathy.

Framework/hypothesis: The experimental group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) are superior to control group A lactulose alone in the reversal of grades for patients of hepatic encephalopathy.

Enrollment: 252 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Both male and female participants with age >18 to <80 years old at the time of consent.
2. Patients with decompensated chronic liver disease (DCLD) confirmed by ultrasound, endoscopy or blood tests associated with overt hepatic encephalopathy grade II-IV according to West Haven Criteria (WHC) will be included.
3. Patients who are unable to talk, their informed consent will be collected from first degree relative and/or legally authorized representative (LAR).
4. The subject/LAR has signed the consent/assent form authorized by the ethics committee, is willing to follow the treatment protocol, and has been informed of the purpose of the study.

Exclusion criteria

1. Participants with age ≤18 years old and ≥ 80 years old and those with grade1covert hepatic encephalopathy according to West Haven Criteria.
2. Patients with comorbidities including ventricular dysfunction and pulmonary edema or neurodegenerative disease (Epilepsy, Parkinson and Drug intoxication), hepatocellular carcinoma (HCC) and with major psychiatric illness (Schizophrenia).
3. Patients with presenting complaint of diarrhea will be excluded.
4. Recent or current use of sedatives or antidepressants and those who are suffering from encephalitis (viral or bacterial), Wernicke and uremic encephalopathy, stroke or brain tumor will not be included.
5. The participant is already participating in another drug trial.
6. Pregnant women will not be included.
7. Subjects suffering from terminal cancers or HIV-AIDS.
8. Participants hypersensitive to lactulose, rifaximin, LOLA and probiotics or any of its excipients will be excluded.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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252 participants in 4 patient groups

Group A (Lactulose)

Active Comparator group

Description:

Participant will receive lactulose syrup (120ml), 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days.

Treatment:

Drug: Lactulose

Group B (Rifaximin + lactulose)

Experimental group

Description:

Participant will receive Rifaximin tablet 550mg (twice daily) BID with lactulose syrup 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days

Treatment:

Drug: Rifaximin plus lactulose

Group C (Probiotic + lactulose)

Experimental group

Description:

Participant will receive Probiotic sachet 2g (twice daily) BID with lactulose syrup 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days

Treatment:

Drug: Probiotic plus lactulose

Group D ( (L-Ornithine L- Aspartate) LOLA + Lactulose)

Experimental group

Description:

Group D: LOLA (L-Ornithine L- Aspartate) concentrate for infusion (5g/10ml = 5g LOLA in 10ml clear solution) + lactulose. Dose: 4 ampoules (40ml) of LOLA 20g of drug diluted in 460ml of 5% dextrose was administered as an intravenous infusion at a rate of 21ml /hour (over 24 hours for 5 days) with lactulose syrup 30ml (three times a day) TDS orally or by nasogastric tube (NG)

Treatment:

Drug: L-ornithine-L-aspartate plus latulose