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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01037959
First received: December 21, 2009
Last updated: October 17, 2013
Last verified: October 2013

December 21, 2009
October 17, 2013
April 2010
November 2014   (final data collection date for primary outcome measure)
Survival rate [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01037959 on ClinicalTrials.gov Archive Site
  • Survival rate [ Time Frame: 12-month follow-up ] [ Designated as safety issue: Yes ]
  • Number of patient with liver transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Complications : bacterial infection, renal insufficiency, hepatic encephalopathy, gastrointestinal bleeding [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Norfloxacin Therapy for Patients With Cirrhosis and Severe Liver Failure
Randomized, Double-Blind, Placebo-Controlled Trial Assessing Norfloxacin in the Prevention of Complications in Patients With Cirrhosis and Severe Liver Failure

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Cirrhosis
  • Drug: Norfloxacin
    400 mg/day (per os) for 6 months
    Other Name: NORFLOXACIN
  • Drug: Placebo
    1 pill/day (per os) for 6 months
    Other Name: PLACEBO
  • Active Comparator: Norfloxacin
    Patients with severe cirrhosis treated with norfloxacin
    Intervention: Drug: Norfloxacin
  • Placebo Comparator: Placebo
    Patients with severe cirrhosis treated with placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
392
November 2015
November 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01037959
P071220
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: MOREAU RICHARD APHP
Assistance Publique - Hôpitaux de Paris
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP