Rifaximin Versus Norfloxacin in Spontaneous Bacterial Peritonitis

NCT04159870 | Unknown Phase 3

• 1 other identifier: RIFA01
• Study Type: interventional
• Target: 322
• Locations: 1 country
• Sites: 1

Brief Summary

Background Prophylaxis of SBP is indicated in three high-risk populations: patients with acute gastrointestinal hemorrhage, patients with low total protein content in ascitic fluid, and patients with a previous history of SBP (secondary prophylaxis). Selective intestinal decontamination with norfloxacin, a quinolone with relatively poor gastrointestinal absorption and with antibacterial activity against GNB, is the most commonly used regimen, but several concerns have been recently raised in this regard. A recent network meta-analysis published by the investigators showed that rifaximin determines interesting results in this setting but needs to be tested in further trials. Given its favorable safety profile and the relatively low cost, rifaximin could represent the antibiotic of choice in long-term prophylaxis. Study Objective To establish the prophylactic efficacy, of rifaximin as compared to norfloxacin in cirrhotic patients with low protein content in the ascitic fluid. Protocol design Phase III, two-arms, open-label, multi-center, randomized controlled trial. Trial population Patients with cirrhosis and ascites and with low protein content in the ascitic fluid (≤1.5 g/dL) and with deteriorated liver function (Child-Pugh score ≥B9, serum bilirubin level ≥3 mg/dL) or impaired renal function (creatinine ≥1.2 mg/dL blood urea nitrogen level ≥25 mg/dL or hyponatremia ≤130 milliequivalent \[mEq\]/L) Protocol Treatments

• The Treatment arm will undergo rifaximin 1200 mg/day in 3 doses.
• The Control arm will undergo norfloxacin 400 mg 1/die for 6 months Primary Endpoint Prevention of spontaneous bacterial peritonitis episodes. Secondary Endpoints
• Prevention of mortality (both all-cause and liver-related mortality)
• Preventions of hepatorenal syndrome
• Prevention of other infections
• Adverse events Sample size and study duration It will be planned to enroll 322 patients (161 per arms) within 18 months. A minimum follow up of 6 months from the last patient recruited will be required.

Conditions

Spontaneous Bacterial Peritonitis

Outcome Measures

Primary Outcomes (1)

• Prevention of Spontaneous Bacterial Peritonitis

  Rate of episodes of spontaneous bacterial peritonitis

  6 months

Secondary Outcomes (4)

• Prevention of mortality

  6 months

• Prevention of hepatorenal syndrome

  6 months

• Prevention of other infections

  6 months

• Adverse Events

  6 months

Study Arms (2)

Intervention Group

EXPERIMENTAL

Rifaximin 1200 mg/day in 3 doses

Drug: Rifaximin

Control Group

ACTIVE COMPARATOR

Norfloxacin 400 mg/day in one dose

Drug: Norfloxacin

Interventions

Rifaximin DRUG

Rifaximin pills 400 mg x 3/day

Intervention Group

Norfloxacin DRUG

Norlfloxacin 400 mg 1 pill/day

Control Group

Eligibility Criteria

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

You may qualify if:

• Adult patients with cirrhosis and ascites and with low protein content in the ascitic fluid (≤1.5 g/dL) and with deteriorated liver function (Child-Pugh score ≥B9, serum bilirubin level ≥3 mg/dL) or impaired renal function (creatinine ≥1.2 mg/dL blood urea nitrogen level ≥25 mg/dL or hyponatremia ≤130 mEq/L)

You may not qualify if:

• Age under 18 years
• Previous history of SBP
• Previous use of antibiotics within the previous two weeks
• Previous GIT bleeding within one month
• Resolving ascites for one month after diuretic therapy
• Liver malignancy, organic renal disease
• Human immunodeficiency virus infection
• Known hypersensitivity to planned drugs
• Refusal to provide informed consent.

Sponsors & Collaborators

• Ospedali Riuniti di Foggia: lead

Study Sites (1)

Ospedali Riuniti Foggia

Foggia, 71122, Italy

Location

Related Publications (9)

• Fernandez J, Navasa M, Gomez J, Colmenero J, Vila J, Arroyo V, Rodes J. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology. 2002 Jan;35(1):140-8. doi: 10.1053/jhep.2002.30082.

  PMID: 11786970 RESULT

• European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417. doi: 10.1016/j.jhep.2010.05.004. Epub 2010 Jun 1. No abstract available.

  PMID: 20633946 RESULT

• Piano S, Brocca A, Mareso S, Angeli P. Infections complicating cirrhosis. Liver Int. 2018 Feb;38 Suppl 1:126-133. doi: 10.1111/liv.13645.

  PMID: 29427501 RESULT

• Soriano G, Guarner C, Tomas A, Villanueva C, Torras X, Gonzalez D, Sainz S, Anguera A, Cusso X, Balanzo J, et al. Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. Gastroenterology. 1992 Oct;103(4):1267-72. doi: 10.1016/0016-5085(92)91514-5.

  PMID: 1397884 RESULT

• Aparicio JR, Such J, Pascual S, Arroyo A, Plazas J, Girona E, Gutierrez A, de Vera F, Palazon JM, Carnicer F, Perez-Mateo M. Development of quinolone-resistant strains of Escherichia coli in stools of patients with cirrhosis undergoing norfloxacin prophylaxis: clinical consequences. J Hepatol. 1999 Aug;31(2):277-83. doi: 10.1016/s0168-8278(99)80225-6.

  PMID: 10453941 RESULT

• Menshawy A, Mattar O, Barssoum K, AboEl-Naga AM, Salim HM, Mohamed AMF, Elgebaly A, Abd-Elsalam S. Safety and Efficacy of Rifaximin in Prophylaxis of Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-analysis. Curr Drug Targets. 2019;20(4):380-387. doi: 10.2174/1389450119666180924145156.

  PMID: 30246636 RESULT

• Facciorusso A, Papagiouvanni I, Cela M, Buccino VR, Sacco R. Comparative efficacy of long-term antibiotic treatments in the primary prophylaxis of spontaneous bacterial peritonitis. Liver Int. 2019 Aug;39(8):1448-1458. doi: 10.1111/liv.14109. Epub 2019 Apr 25.

  PMID: 30920712 RESULT

• Goel A, Rahim U, Nguyen LH, Stave C, Nguyen MH. Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis. Aliment Pharmacol Ther. 2017 Dec;46(11-12):1029-1036. doi: 10.1111/apt.14361. Epub 2017 Oct 9.

  PMID: 28994123 RESULT

• 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

MeSH Terms

Interventions

Rifaximin; Norfloxacin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: November 5, 2019
• Primary Completion: November 20, 2021
• Study Completion: December 20, 2021
• Last Updated: February 16, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)