Norfloxacin Versus Ciprofloxacin for Spontaneous Bacterial Peritonitis (SBP) Prevention

Adverse Reaction to Other Drugs and Medicines Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01542801
• Other study ID #: SBP_prevention
• Status: Completed
• Phase: Phase 4
• First received: February 26, 2012
• Last updated: December 27, 2016
• Start date: August 2011
• Est. completion date: April 2016

Study information

• Verified date: December 2016
• Source: Korea University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: April 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Adverse Reaction to Other Drugs and Medicines
• Peritonitis

Intervention

Drug:
• Norfloxacin
Norfloxacin 400 mg per day
• ciprofloxacin
Ciprofloxacin 750 mg per week

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan	Gyeonggi-do
Korea, Republic of	Soonchunhyang University College of Medicine, Bucheon Hospital	Bucheon
Korea, Republic of	Soonchunhyang University College of Medicine, Cheonan Hospital	Cheonan
Korea, Republic of	Kyungpuk National University Hospital	Daegu
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Soonchunhyang University College of Medicine, Seoul Hospital	Seoul
Korea, Republic of	Sungkyunkwan University Gangbuk Samsung Hospital	Seoul

Sponsors (4)

Lead Sponsor	Collaborator
Korea University	Kyungpook National University, Soon Chun Hyang University, Sungkyunkwan University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

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. Review. — View Citation

Fernández J, Navasa M, Gómez J, Colmenero J, Vila J, Arroyo V, Rodés J. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology. 2002 Jan;35(1):140-8. — View Citation

Fernández J, Navasa M, Planas R, Montoliu S, Monfort D, Soriano G, Vila C, Pardo A, Quintero E, Vargas V, Such J, Ginès P, Arroyo V. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. G — View Citation

Grangé 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 randomize — View Citation

Koulaouzidis A, Bhat S, Karagiannidis A, Tan WC, Linaker BD. Spontaneous bacterial peritonitis. Postgrad Med J. 2007 Jun;83(980):379-83. Review. — View Citation

Mowat C, Stanley AJ. Review article: spontaneous bacterial peritonitis--diagnosis, treatment and prevention. Aliment Pharmacol Ther. 2001 Dec;15(12):1851-9. Review. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	1 year mortality	liver related mortality and overall mortality will be assessed.	12 months ( 1 year)	Yes
Secondary	Incidence of infectious event other than SBP	Bacteremia, urinary tract infection, pneumonia, and other infections will be included.	12 months	Yes
Secondary	Hepatorenal syndrome	Diagnostic criteria of hepatorenal syndrome is defined by the latest version of Internation ascites club consensus.	12 months	Yes
Secondary	Hepatic encephalopathy	Will follow the Western Heaven Criteria.	12 months	Yes
Secondary	Adverse event of drugs	Any of adverse event suspected by study drugs will be recorded.	12 months	Yes

External Links

•   Korea University (PI of SBP_prevention study is belong to this university)
•   Liver cirrhosis clinical research center (PI of SBP_prevention study is belong to this center)