Norfloxacin Versus Ciprofloxacin for Spontaneous Bacterial Peritonitis (SBP) Prevention

Study Overview
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Brief Summary
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For the prevention of spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis, norfloxacin 400mg per day is a standard regimen. Ciprofloxacin 750 mg per week is also known to be effective for prevention of SBP. In addition, ciprofloxacin once weekly administration is more convenient and less costly. Therefore ciprofloxacin once weekly could be more useful if the the efficacy is comparable to norfloxacin once daily. This study aims to prove ciprofloxacin once weekly administration is as effective as norfloxacin once daily administration for the prevention of SBP in cirrhotic patients with ascites.

Detailed Description
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Spontaneous bacterial peritonitis (SBP) is one of the most serious complication of liver cirrhosis. The short term mortality reaches 20-30% mainly due to sepsis, hepatorenal syndrome, and liver failure. In addition, patients who suffered SBP show poor prognosis with 1 year-mortality of 50-70%. The high recurrence rate is also problematic. Therefore appropriate prevention of SBP is critically needed to improve survival as well as quality of life. Selective intestinal decontamination (SID) is eradicating gram negative bacterial in the gut lumen, and effectively prevent development of SBP. Patients with gastrointestinal hemorrhage, low ascitic protein level, high bilirubin, or history of SBP need SID. Norfloxacin 400 mg daily administration decreased the incidence of SBP to 2% compared with 17% of no prevention group's among patients with ascitic protein less than 1.5 g/dL. Also, in high risk patients (Child-Pugh score > or = 9 points and serum bilirubin level > or = 3 mg/dL, serum creatinine level > or = 1.2 mg/dL, blood urea nitrogen level > or = 25 mg/dL, or serum sodium level < or = 130 mEq/L), norfloxacin 400 mg/day improved 1 year-survival to 60% compared with 48% of no prevention group's. Therefore norfloxacin is now primarily recommend for the prevention of SBP in cirrhotic patients. However, norfloxacin should be administered on daily basis, so efforts to reduce cost and frequency have been made. Ciprofloxacin 750 mg weekly administration has been evaluated, and shown to be effective as 3.6% versus 22% in prevention versus no prevention arm, respectively. Therefore, ciprofloxacin 750 mg/week is a reasonable option for prevention of SBP. However, comparison of efficacy of these two methods (norfloxacin 400 mg daily versus ciprofloxacin 750 mg weekly) has not been performed, yet. The investigators aim to compare the efficacy and safety of norfloxacin 400 mg daily and ciprofloxacin 750 mg weekly for the proper management of cirrhotic patients with ascites.

Official Title
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Comparison of Daily Norfloxacin Versus Weekly Ciprofloxacin for the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients

Conditions
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Adverse Reaction to Other Drugs and Medicines

Intervention / Treatment
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* Drug: Norfloxacin
* Drug: ciprofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20-75 years old Liver cirrhosis with ascites Ascitic polymorphonucleated cells (PMN) count < 250/mm3 Ascitic protein <= 1.5 g/dL or History of SBP Exclusion Criteria: Incompatibility with inclusion criteria Hypersensitivity or intolerability with quinolones Hepatocellular carcinoma beyond Milan Criteria Hepatic encephalopathy over stage 2 History of treatment with antibiotics within 2 weeks of enrollment HIV infection Untreated malignancy Women with child-bearing age not willing to use effective contraception. Pregnant or breast feeding women Not able to give informed consents

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Norfloxacin<br>norfloxacin 400 mg once daily administration | Drug: Norfloxacin<br>* Norfloxacin 400 mg per day<br>|
| Experimental: Ciprofloxacin<br>Ciprofloxacin 750 mg per week | Drug: ciprofloxacin<br>* Ciprofloxacin 750 mg per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The prevention rate of spontaneous bacterial peritonitis (SBP) | The incidence of SBP will measured in each the group. Thereby, prevention rate will also be compared between the groups. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year mortality | liver related mortality and overall mortality will be assessed. | 12 months ( 1 year) | 
| Incidence of infectious event other than SBP | Bacteremia, urinary tract infection, pneumonia, and other infections will be included. | 12 months | 
| Hepatorenal syndrome | Diagnostic criteria of hepatorenal syndrome is defined by the latest version of Internation ascites club consensus. | 12 months | 
| Hepatic encephalopathy | Will follow the Western Heaven Criteria. | 12 months | 
| Adverse event of drugs | Any of adverse event suspected by study drugs will be recorded. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect of Preventive Antibiotics