Effectiveness of Oral Lactulose Versus Lactulose Enema in Hepatic Encephalopathy

Khyber Medical College, Peshawar

Status and phase: Not yet enrolling; Phase 4

Conditions: Hepatic Encephalopathy; Chronic Liver Disease

Treatments: Drug: Tap water; Drug: Lactulose

Study type: Interventional

Funder types: Other

Identifiers

NCT05788627

700

Details and patient eligibility

About

Patients with chronic liver disease due to hepatitis B or C viruses, Non-alcoholic fatty liver disease, autoimmune hepatitis, wilson disease, cryptogenic hepatitis etc are prone to develop complications. Hepatic encephalopathy is one of such complications. It is graded into four types depending on severity of clinical features, which range through altered sleep pattern to coma. The current study aims to compare the effectiveness of lactulose enema with oral lactulose in time to recovery from higher grade of encephalopathy to lower grade of encephalopathy.

Full description

Hepatic encephalopathy (HE) is defined as neuropsychiatric disorder due to liver failure. It is characterized by mild cognitive impairment, stupor and coma. The most common reasons for pathogenesis include the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. Neurotoxin ammonia is related to precipitating HE, for which the gastrointestinal tract is the primary source. Colonic bacteria catabolise the nitrogenous sources into ammonia.

Lactulose is the initial treatment for HE. It produces diarrhea by osmosis and reduces pH of colonic contents, which leads to reduced absorption of ammonia by converting it to ammonium ion (NH4). Understandingly, it does not cure the underlying liver disease however, it does prevent deterioration of the mental status in HE.

Initial oral dose of lactulose is 30 ml once a day or twice daily. For retention enema the dose is 300 ml lactulose plus 700 ml water, administered every 4 hours. It can be increased as tolerated. At least, 2-4 loose stools per day should be passed by the patient.

Lactulose is also effective as primary prophylaxis against the development of HE.

Constipation is one very common precipitating factor for hepatic encephalopathy which is routinely managed with oral lactulose or kleen enema (21.4g (18.1% w/v) Sodium Dihydrogen Phosphate Dihydrate and 9.4g (8.0% w/v) Disodium Phosphate Dodecahydrate). Lactulose enema is also given to patients in hepatic encephalopathy either alone or in combination with oral lactulose. However it is not clear whether there is any difference in the efficacy of oral or enema lactulose in patients with hepatic encephalopathy in terms of improvement of encephalopathy grade and time to improvement. This study aims to determine the efficacy of oral versus enema lactulose in the achievement of these goals.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female cirrhotic patients in grades 3 or 4 of hepatic encephalopathy
• Patient with constipation as the precipitating factor will be included in the study

Exclusion criteria

• Patients with dehydration
• Electrolyte abnormalities
• Spontaneous bacterial peritonitis (SBP),
• Fever
• Using sedative / hypnotic medications as predisposing factors for hepatic encephalopathy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups, including a placebo group

Placebo arm / tap water enema arm

Placebo Comparator group

Description:

This arm will receive oral lactulose as per treatment protocol for hepatic encephalopathy i.e. 30ml twice daily. And will receive tap water enema as placebo i.e. 1000ml tap water enema twice daily.

Treatment:

Drug: Tap water

Lactulose enema arm

Experimental group

Description:

This arm will receive oral lactulose in a dose of 30ml twice daily alongwith lactulose enema (300ml lactulose plus 700ml water) twice daily.

Treatment:

Drug: Lactulose