Clinical trial NCT01542801: Norfloxacin Versus Ciprofloxacin for Spontaneous Bacterial Peritonitis (SBP) Prevention
Official title: Comparison of Daily Norfloxacin Versus Weekly Ciprofloxacin for the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Adverse Reaction to Other Drugs and Medicines
Keywords: Effect of Preventive Antibiotics
Lead sponsor: Korea University
Sponsor class: OTHER
Collaborators: name: Sungkyunkwan University
name: Kyungpook National University Hospital
name: Soon Chun Hyang University
First posted: 2012-03-02
Enrollment: 124
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: * 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The prevention rate of spontaneous bacterial peritonitis (SBP)
timeFrame: 12 months
Secondary outcomes:
measure: 1 year mortality
timeFrame: 12 months ( 1 year)
measure: Incidence of infectious event other than SBP
timeFrame: 12 months
measure: Hepatorenal syndrome
timeFrame: 12 months
measure: Hepatic encephalopathy
timeFrame: 12 months
measure: Adverse event of drugs
timeFrame: 12 months
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University College of Medicine, Bucheon Hospital
city: Cheonan
country: Korea, Republic of
facility: Soonchunhyang University College of Medicine, Cheonan Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University College of Medicine, Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Sungkyunkwan University Gangbuk Samsung Hospital
Study officials:
affiliation: Korea University Anam Hospital
name: Soon Ho Um, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Ansan Hospital
name: Hyung Joon Yim, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Mowat C, Stanley AJ. Review article: spontaneous bacterial peritonitis--diagnosis, treatment and prevention. Aliment Pharmacol Ther. 2001 Dec;15(12):1851-9. doi: 10.1046/j.1365-2036.2001.01116.x.
citation: Koulaouzidis A, Bhat S, Karagiannidis A, Tan WC, Linaker BD. Spontaneous bacterial peritonitis. Postgrad Med J. 2007 Jun;83(980):379-83. doi: 10.1136/pgmj.2006.056168.
citation: 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.
citation: 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.
citation: Rolachon A, Cordier L, Bacq Y, Nousbaum JB, Franza A, Paris JC, Fratte S, Bohn B, Kitmacher P, Stahl JP, et al. Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial. Hepatology. 1995 Oct;22(4 Pt 1):1171-4. doi: 10.1016/0270-9139(95)90626-6.
citation: Grange JD, Roulot D, Pelletier G, Pariente EA, Denis J, Ink O, Blanc P, Richardet JP, Vinel JP, Delisle F, Fischer D, Flahault A, Amiot X. Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial. J Hepatol. 1998 Sep;29(3):430-6. doi: 10.1016/s0168-8278(98)80061-5.
citation: Fernandez J, Navasa M, Planas R, Montoliu S, Monfort D, Soriano G, Vila C, Pardo A, Quintero E, Vargas V, Such J, Gines P, Arroyo V. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007 Sep;133(3):818-24. doi: 10.1053/j.gastro.2007.06.065. Epub 2007 Jul 3.