Norfloxacin Therapy for Patients With Cirrhosis and Severe Liver Failure

2014-08-27 03:17:05 | BioPortfolio


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; patients with either previous history of SBP or of norfloxacin prophylaxis, allergy to quinolones, severe acute alcoholic hepatitis, 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.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention


Severe Cirrhosis


Norfloxacin, Placebo


Assisatnce publique Hoptitaux de Paris




Assistance Publique - Hôpitaux de Paris

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:17:05-0400

Clinical Trials [991 Associated Clinical Trials listed on BioPortfolio]

Evaluation of Safety & Efficacy of Synbiotic on the Incidence and Recurrence of Spontaneous Bacterial Peritonitis (SBP) in Cirrhotics

Background: Spontaneous bacterial peritonitis (SBP) is a serious complication in patients of cirrhosis with ascites and may occur despite antibiotic prophylaxis. Small bowel dysmotility an...

A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome

The hepatopulmonary syndrome (HPS)and pre-HPS is a disease seen in patients with chronic liver disease, whereby patients develop dilations in the blood vessels of the lungs, resulting in l...

Norfloxacin In The Primary Prophylaxis Of Spontaneous Bacterial Peritonitis

Advanced liver disease and low ascitic fluid protein concentration have been identified as risk factors for spontaneous bacterial peritonitis in cirrhosis. Moreover, renal impairment and h...

Comparison of the Efficacy of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Norfloxacin in Secondary Prophylaxis for Spontaneous Bacterial Peritonitis

-Consecutive patients of decompensated cirrhosis of any etiology, presenting to the Institute of Liver and Biliary Sciences hospital with spontaneous bacterial peritonitis will be evaluate...

Rifaximin and Norfloxacin for Prevention of SBP in Adults With Decompensated Cirrhosis

Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhotic patients with ascites.Early diagnosis and prompt treatment with effective antibiotics significant...

PubMed Articles [5737 Associated PubMed Articles listed on BioPortfolio]

Effects of Long-term Norfloxacin Therapy in Patients with Advanced Cirrhosis.

There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatmen...

Successful Distal Gastrectomy for Gastric Cancer with Child-Pugh Class B Alcoholic Liver Cirrhosis.

Extended lymph node dissection in patients with gastric cancer with liver cirrhosis can lead to severe morbidity and mortality, especially in those with Child-Pugh class B or C cirrhosis. We, herein, ...

DNA influence on norfloxacin fluorescence.

The emission properties of norfloxacin, a quinolone antibiotic, in presence of salmon sperm DNA were studied at room temperature and in conditions of acid, alkaline and neutral pH. It was found that n...

Efficacy and Safety of Abrilumab in a Randomized, Placebo-Controlled Trial for Moderate to Severe Ulcerative Colitis.

αβ integrin is a validated target in inflammatory bowel disease. This randomized, phase 2b, placebo-controlled, double-blind study evaluated the efficacy and safety of the anti-αβ antibody abrilum...

Emricasan (IDN-6556) Lowers Portal Pressure in Patients with Compensated Cirrhosis and Severe Portal Hypertension.

Caspases play a central role in apoptosis, inflammation and fibrosis. They produce hemodynamically-active, pro-inflammatory microparticles that cause intrahepatic inflammation, vasoconstriction and ex...

Medical and Biotech [MESH] Definitions

A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE.

Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.

FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.

More From BioPortfolio on "Norfloxacin Therapy for Patients With Cirrhosis and Severe Liver Failure"

Quick Search


Relevant Topic

Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Searches Linking to this Trial