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Norfloxacin Therapy for Patients With Cirrhosis and Severe Liver Failure (NORFLOCIR)

This study has been terminated.
(lack of recruitement)
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris Identifier:
First received: December 21, 2009
Last updated: December 8, 2015
Last verified: November 2015
Patients with advanced cirrhosis have abnormal translocation of Gram-negative bacteria across the intestinal barrier and subsequent systemic inflammatory response. We hypothesized that this translocation may worsen the underlying liver disease. Thus, the aim of this trial was to assess the effects of the oral administration of norfloxacin (an antibiotic that suppresses intestinal Gram-negative bacteria) on the development of complications of cirrhosis.

Condition Intervention Phase
Drug: Norfloxacin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized, Double-Blind, Placebo-Controlled Trial Assessing Norfloxacin in the Prevention of Complications in Patients With Cirrhosis and Severe Liver Failure

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Survival rate [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Survival rate [ Time Frame: 12-month follow-up ]
  • Number of patient with liver transplantation [ Time Frame: 12 months ]
  • Complications : bacterial infection, renal insufficiency, hepatic encephalopathy, gastrointestinal bleeding [ Time Frame: 12 months ]

Enrollment: 291
Study Start Date: April 2010
Study Completion Date: November 2015
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Norfloxacin
Patients with severe cirrhosis treated with norfloxacin
Drug: Norfloxacin
400 mg/day (per os) for 6 months
Placebo Comparator: Placebo
Patients with severe cirrhosis treated with placebo
Drug: Placebo
1 pill/day (per os) for 6 months

Detailed Description:

Intestinal translocation of Gram-negative bacteria occurs in patients with advanced cirrhosis. Long-term oral administration of 400 mg/day of norfloxacin (a fluoroquinolone antibiotic) is known to induce selective intestinal decontamination against Gram-negative bacteria. A randomized, double-blind, placebo-controlled trial of oral norfloxacin (400 mg/day for 1 year) has been conducted in a small series of patients with advanced cirrhosis and low ascitic fluid protein concentrations <1.5 g/dL. This trial showed that norfloxacin therapy significantly increased the 1-year probability of being free of a first episode of spontaneous bacterial peritonitis (SBP) and improved 3-month survival. In this previous study, oral norfloxacin therapy was also found to decrease the risk of development of hepatorenal syndrome, a very severe complication of cirrhosis. It has been suggested that bacterial translocation, through the release of bacterial byproducts, results in systemic inflammation and subsequent systemic vasodilation which precipitates hepatorenal syndrome. Since systemic vasodilation plays a role in the development of ascites, bacterial byproducts via circulatory alterations may contribute to mechanisms leading to ascites formation. It is important to note that a randomized, double-blind, placebo-controlled trial of oral administration of the quinolone ciprofloxacin (500 mg/day for 1 year) has been conducted in a small series of patients with moderately severe cirrhosis, low ascitic fluid protein concentrations (<1.5 g/dL) and no prior history of SBP. However, ciprofloxacin therapy did not significantly increase the 1-year probability of being free of SBP. Taken together the findings of these 2 previous small-size trials suggest that long-term oral quinolone therapy is effective mainly in patients with severe cirrhosis. This is why we decided to perform a large multicenter, randomized, parallel, placebo-controlled trial assessing the effects of norfloxacin on survival in patients with cirrhosis and severe liver failure (Child-Pugh grade C). In addition, the effects of norfloxacin on the development of main complications of cirrhosis will be investigated.

The primary outcome measure will be 6-month survival. The secondary outcome measures will be the proportion of transplanted patients, the occurrence of complications (bacterial infection, renal failure, hepatic encephalopathy and gastrointestinal bleeding). All adult patients with severe cirrhosis might be randomized after written consent. Pregnant persons; patient who has been treated with a quinolone in the month before the inclusion, allergy to quinolones, hepatocellular carcinoma, or HIV infection will not be included. Patients receive either norfloxacin or placebo once a day for 6 months. Three hundred and ninety-two patients are necessary to decrease 6-month mortality rate from 40% in the placebo group to 25% in the norfloxacin group with a beta risk of 90% and an alpha risk of 5%. Patients will be followed-up every month during 6 months and at 9 and 12 months.


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

Inclusion Criteria:

  • Age > 18 years,
  • Liver failure as defined by a Child-Pugh score ≥ 10 points,
  • Accept to participate,
  • Have health insurance.

Exclusion Criteria:

  • Pregnancy,
  • Patient who has been treated with a quinolone in the month before his inclusion
  • Allergy to quinolones,
  • Hepatocellular carcinoma, and
  • HIV infection.
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Please refer to this study by its identifier: NCT01037959

Assisatnce publique Hoptitaux de Paris
Clichy, France, 92110
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: MOREAU RICHARD APHP
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01037959     History of Changes
Other Study ID Numbers: P071220
Study First Received: December 21, 2009
Last Updated: December 8, 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:
severe cirrhosis
Patients with severe cirrhosis

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Failure
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hepatic Insufficiency
Anti-Bacterial Agents
Anti-Infective 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 processed this record on May 25, 2017