Norfloxacin Versus Ciprofloxacin for Spontaneous Bacterial Peritonitis (SBP) Prevention

NCT ID: NCT01542801

Last Updated: 2016-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2016-04-30

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.

Conditions

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Adverse Reaction to Other Drugs and Medicines

Keywords

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Effect of Preventive Antibiotics

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Norfloxacin

norfloxacin 400 mg once daily administration

Group Type ACTIVE_COMPARATOR

Norfloxacin

Intervention Type DRUG

Norfloxacin 400 mg per day

Ciprofloxacin

Ciprofloxacin 750 mg per week

Group Type EXPERIMENTAL

ciprofloxacin

Intervention Type DRUG

Ciprofloxacin 750 mg per week

Interventions

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Norfloxacin

Norfloxacin 400 mg per day

Intervention Type DRUG

ciprofloxacin

Ciprofloxacin 750 mg per week

Intervention Type DRUG

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

* 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
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sungkyunkwan University

OTHER

Sponsor Role collaborator

Kyungpook National University Hospital

OTHER

Sponsor Role collaborator

Soon Chun Hyang University

OTHER

Sponsor Role collaborator

Korea University

OTHER

Sponsor Role lead

Responsible Party

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Soon Ho Um

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Soon Ho Um, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Korea University Anam Hospital

Hyung Joon Yim, M.D., Ph.D.

Role: STUDY_DIRECTOR

Korea University Ansan Hospital

Locations

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Korea University Ansan Hospital

Ansan, Gyeonggi-do, South Korea

Site Status

Soonchunhyang University College of Medicine, Bucheon Hospital

Bucheon-si, , South Korea

Site Status

Soonchunhyang University College of Medicine, Cheonan Hospital

Cheonan, , South Korea

Site Status

Kyungpuk National University Hospital

Daegu, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Soonchunhyang University College of Medicine, Seoul Hospital

Seoul, , South Korea

Site Status

Sungkyunkwan University Gangbuk Samsung Hospital

Seoul, , South Korea

Site Status

Countries

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South Korea

References

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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.

Reference Type BACKGROUND
PMID: 11736714 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17551068 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11786970 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20633946 (View on PubMed)

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.

Reference Type RESULT
PMID: 7557868 (View on PubMed)

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.

Reference Type RESULT
PMID: 9764990 (View on PubMed)

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.

Reference Type RESULT
PMID: 17854593 (View on PubMed)

Related Links

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http://www.korea.ac.kr

Korea University (PI of SBP\_prevention study is belong to this university)

Other Identifiers

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SBP_prevention

Identifier Type: -

Identifier Source: org_study_id