Rifaximin and Norfloxacin for Prevention of SBP in Adults With Decompensated Cirrhosis

NCT03695705 | Completed Phase 3 DMC

• 1 other identifier: PGIMER
• Study Type: interventional
• Target: 142
• Locations: 0 countries
• Sites: N/A

Brief Summary

Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhotic patients with ascites.Early diagnosis and prompt treatment with effective antibiotics significantly improves the prognosis of this complication. The recommended treatment is a third generation cephalosporin given intravenously for five days.Following recovery patients should receive secondary prophylaxis with a quinolone such as oral norfloxacin 400 mg/day.Also all patients should be assessed for liver transplantation. Most commonly used antibiotic for both primary and secondary prophylaxis is norfloxacin 400 mg once daily.Other antibiotics like cotrimoxazole,ceftriaxone,ciprofloxacin and rifaximin have also been evaluated in various studies.Use of antibiotic prophylaxis has been evaluated to decrease recurrence of SBP in treated groups than in control groups. Rifaximin is an oral antimicrobial agent with broad-spectrum activity that is gut-selective and nonsystemic. Rifaximin appears to have a low level of selection for resistant bacterial mutants. Intestinal decontamination is known to increase peripheral blood counts by suppressing endotoxemia and inhibiting the effects of cytokines and nitric oxide on blood counts. With this mechanisms rifaximin has been already proven to decrease recurrence of hepatic encephalopathy.The most important mechanism for development of SBP is bacterial translocation (BT).Translocation of enteric flora occurs via defective mucosal barrier.BT is considered the key step in pathogenesis of SBP and cirrhotic patients.It is also the critical factor that is responsible for host immune response and secreation of inflammatory mediators that is responsible for hemodynamic changes in cirrhotics.Three most important mechanism of bacterial translocation include bacterial overgrowth,physical disruption of gut mucosal barrier and impaired host defence. Rifaximin by mechanism of gut decontamination may reduce translocation of intestinal bacteria into mesenteric lymph nodes then into ascitic fluid.Thus it may prove useful in preventing recurrence of SBP.There was no study till date that has compared efficacy of Norfloxacin and rifaximin to prevent development of SBP.This pilot study was done to compare the efficacy of rifaximin with norfloxacin in both primary and secondary prophylaxis of SBP in a prospective randomized open-label and non-inferiority trial

Conditions

Cirrhosis, Liver

Keywords

Norfloxacin,Rifaximin,Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Incidence SBP in patients on Rifaximin prophylaxis compared to Norfloxacin

  Incidence of development of SBP in patients with(Secondary prophylaxis) or without(Primary prophylaxis) in patients on Rifaximin compared to norfloxacin

  6 months

Secondary Outcomes (3)

• Incidence of hepatic encephalopathy

  6 months

• Incidence of overall mortality

  6 months

• Incidence of development of sepsis

  6 months

Study Arms (2)

Primary prophylaxis arm

OTHER

28 Patients with decompensated cirrhosis without past history of SBP were randomised to receive Rifaximin at dose 550 mg twice daily.29 Patients with decompensated cirrhosis without past history of SBP were randomized to receive Norfloxacin at dose 400 mg once daily

Drug: Rifaximin 550 mg twice a day and Norfloxacin 400 mg once a day

Secondary prophylaxis arm

OTHER

26 Patients with decompensated cirrhosis with past history of SBP were randomized to receive Rifaximin at dose 550 mg twice daily.33 Patients with decompensated cirrhosis with past history of SBP were randomized to receive Norfloxacin at dose 400 mg once daily

Drug: Rifaximin 550 mg twice a day and Norfloxacin 400 mg once a day

Interventions

Rifaximin 550 mg twice a day and Norfloxacin 400 mg once a day DRUG

Patients on Rifaximin prophylaxis will be given 550 mg twice daily and on Norfloxacin prophylaxis will receive Norfloxacin 400 mg once daily for 6 months

Primary prophylaxis arm; Secondary prophylaxis arm

Eligibility Criteria

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

You may qualify if:

• Low Ascitic fluid protein level \<1gm/dl
• Advanced liver disease as evidenced by CTP≥9
• Serum billirubin≥3 mg/dl
• Impaired renal function defined by serum creatinine≥1.2 mg/dl
• Blood urea nitrogen 25mg/dl
• Serum sodium level≤ 1.2 meq/l

You may not qualify if:

• Inability to obtain informed consent from patient or relatives.
• Acute on chronic liver failure
• Severe cardiopulmonary disease
• Pregnancy
• Age \<18yrs
• Post liver transplant patients
• HIV infection
• Recent abdominal surgery(with in last 6 months)
• Portal vein thrombosis
• Splenectomy
• Patient on immunosuppressive drugs except for alcoholic steatohepatitis
• Patients on psychoactive drugs, such as antidepressants or sedatives
• Hypersensitivity to norfloxacin and rifaximin
• Malignancies including Hepatocellular carcinoma
• Prior history of hepatic encephalopathy on Rifaximin -

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: 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

• Praharaj DL, Premkumar M, Roy A, Verma N, Taneja S, Duseja A, Dhiman RK. Rifaximin Vs. Norfloxacin for Spontaneous Bacterial Peritonitis Prophylaxis: A Randomized Controlled Trial. J Clin Exp Hepatol. 2022 Mar-Apr;12(2):336-342. doi: 10.1016/j.jceh.2021.08.010. Epub 2021 Aug 18.

  PMID: 35535057 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Rifaximin; Norfloxacin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 Officials

• RADHA K DHIMAN, DM,FRCP

  Post Graduate Institute of Medical Education and Research, Chandigarh

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 4, 2018
• Study Start: January 1, 2016
• Primary Completion: December 31, 2016
• Study Completion: June 30, 2017
• Last Updated: October 4, 2018

Record last verified: 2018-10