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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03695705
Recruitment Status : Completed
First Posted : October 4, 2018
Last Update Posted : October 4, 2018
Sponsor:
Information provided by (Responsible Party):
Radha K Dhiman, Postgraduate Institute of Medical Education and Research

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


Condition or disease Intervention/treatment Phase
Cirrhosis, Liver Drug: Rifaximin 550 mg twice a day and Norfloxacin 400 mg once a day Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Randomized Control Trial of Rifaximin and Norfloxacin in Primary and Secondary Prophylaxis of Spontaneous Bacterial Peritonitis(SBP) in Cirrhotic Patients
Actual Study Start Date : January 1, 2016
Actual Primary Completion Date : December 31, 2016
Actual Study Completion Date : June 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis
Drug Information available for: Rifaximin

Arm Intervention/treatment
Primary prophylaxis arm
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
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

Secondary prophylaxis arm
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
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 Outcome Measures :
  1. Incidence SBP in patients on Rifaximin prophylaxis compared to Norfloxacin [ Time Frame: 6 months ]
    Incidence of development of SBP in patients with(Secondary prophylaxis) or without(Primary prophylaxis) in patients on Rifaximin compared to norfloxacin


Secondary Outcome Measures :
  1. Incidence of hepatic encephalopathy [ Time Frame: 6 months ]
    Incidence of development of hepatic encephalopathy in patients on Rifaximin prophylaxis compared to Norfloxacin prophylaxis

  2. Incidence of overall mortality [ Time Frame: 6 months ]
    Incidence of mortality in patients on Rifaximin prophylaxis compared to Norfloxacin prophylaxis

  3. Incidence of development of sepsis [ Time Frame: 6 months ]
    Incidence of development of sepsis in patients on Rifaximin prophylaxis compared to Norfloxacin prophylaxis



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03695705


Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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Principal Investigator: RADHA K DHIMAN, DM,FRCP Postgraduate Institute of Medical Education and Research

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Responsible Party: Radha K Dhiman, Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03695705    
Other Study ID Numbers: PGIMER
First Posted: October 4, 2018    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Radha K Dhiman, Postgraduate Institute of Medical Education and Research:
Norfloxacin,Rifaximin,Prophylaxis
Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Rifaximin
Norfloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors