Microbial Resistance of Rifaximin in Hepatic Encephalopathy

NCT04736836 | Completed Phase 4 DMC

• 1 other identifier: CL(1173)
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Aims and Objectives: To determine the safety and efficacy of rifaximin plus lactulose as secondary prophylaxis of HE compared to lactulose alone. To evaluate the effect of long-term administration of rifaximin on development of resistant mutants and investigating its correlation with its efficacy. Methods: An open label parallel, prospective interventional study was conducted. One hundred patients experienced at least one attack of hepatic encephalopathy were included in the study. Patients were randomly allocated either to receive rifaximin plus lactulose or lactulose alone for 6 months. Conn score, Model of End stage Liver Disease (MELD) score, asterixis grade, complete blood count (CBC), liver function tests, kidney function tests, urine and stool analysis and abdominal ultrasonography were compared in both groups. The primary efficacy endpoint was the time to the first breakthrough. The secondary efficacy endpoint was the time to the first hospitalization involving HE. Safety assessment was done by reporting any adverse events, serious adverse events and by repeating biochemical evaluation every 2 weeks. Determination of the minimum inhibitory concentration (MIC) of rifaximin for lactose fermenter isolates was done for the entire patients before starting treatment and at the end of treatment.

Conditions

Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (1)

• the time to the first breakthrough episode of OHE the time to the first breakthrough episode of OHE (overt hepatic encephalopathy)

  (defined as the time from the first dose of the study drug to an increase from a baseline Conn score of 0 or 1 to a score of 2 or more or from a baseline Conn score of 0 to a Conn score of 1 plus a 1-unit increase in the asterixis grade.

  6 months

Study Arms (2)

interventional

ACTIVE COMPARATOR

50 patient take rifaximin plus lactulose for 6 months

Drug: Rifaximin

control

PLACEBO COMPARATOR

50 patient take lactulose for 6 months

Drug: Rifaximin

Interventions

Rifaximin DRUG

locally absorbed antibiotic

control; interventional

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• cirrhosis due to HCV infection
• age 18 to 75 years,
• experiencing at least one episode of OHE,
• MELD score ≤ 25

You may not qualify if:

• Patients with neurological or communication problems,
• hepatocellular carcinoma
• diabetes mellitus
• active infection
• serum creatinine \> 2 mg/dl, Hg \< 8 g/dL, serum Na \< 125 mmol/L or serum K \< 2.5 mmol/L .
• Patients with previous intake of rifaximin as prophylaxis or any antibiotic within the last month

Sponsors & Collaborators

• National Hepatology & Tropical Medicine Research Institute: lead

Related Publications (2)

• Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.

  PMID: 37467180 DERIVED

• Abdel Moneim M, Abdelaziz DH, Ibrahim Nagy Y, Abdel Baki A, Attia AS, Sabry N. Rifaximin microbial resistance and its efficacy and safety as a secondary prophylaxis of hepatic encephalopathy in patients with hepatitis C virus-related cirrhosis. Int J Clin Pract. 2021 Nov;75(11):e14807. doi: 10.1111/ijcp.14807. Epub 2021 Sep 17.

  PMID: 34487412 DERIVED

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Part-Time Lecturer of pharmacy practice & clinical Pharmacy at Future University in Egypt

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: February 3, 2021
• Study Start: January 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: February 3, 2021

Record last verified: 2021-02