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A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome

This study has been completed.
Sponsor:
Collaborator:
University of Toronto
Information provided by:
St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT00362752
First received: August 8, 2006
Last updated: January 26, 2010
Last verified: January 2010
  Purpose

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 low oxygen levels and shortness of breath.

In this study, each HPS and pre-HPS subject will be treated with a commonly used antibiotic called "norfloxacin" (approved for use in the treatment of gonorrhea, prostatitis and urinary tract infections) for a 4-week period. In order to ensure that any observed improvement was indeed due to norfloxacin, each subject will also be treated with a separate 4-week course of an identical placebo. There will also be a 4 week wash-out period (no study medication/placebo) between the 2 courses of treatment.

The primary aim of the study will be to measure improvements in oxygen levels while on norfloxacin, although a number of secondary parameters will also be followed.


Condition Intervention Phase
Hepatopulmonary Syndrome
Drug: Norfloxacin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome

Resource links provided by NLM:


Further study details as provided by St. Michael's Hospital, Toronto:

Primary Outcome Measures:
  • - Primary endpoint: A-a gradient [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • paO2, [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • exhaled NO [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • DLCO [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • 6MWD [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • CO [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • TPR [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • PAP (on echocardiogram) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • endotoxin levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • ET-1 levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • MELD score [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • bilirubin and INR [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • BDI [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • TDI [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • CRQ [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2006
Study Completion Date: December 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo 400 mg po bid
Experimental: Norfloxacin 400 mg bid Drug: Norfloxacin
400 mg po bid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Diagnosis of HPS, based on all of the following:

evidence of portal hypertension (esophagogastric varices or portal hypertensive gastropathy identified on esophagogastroduodenoscopy, and/or varices seen on computerized tomography (CT) scan or ultrasound, and/or splenomegaly with no other explanation, and/or ascites with no other explanation, and/or hepatic vein wedge pressure greater than 12 mm Hg) Intrapulmonary shunt on contrast echocardiography (CE) AaDO2 greater than 20 mm Hg on standing, room air arterial blood gas (ABG) OR

Pre-HPS with elevated exhaled Nitric Oxide:

evidence of portal hypertension (esophagogastric varices or portal hypertensive gastropathy identified on esophagogastroduodenoscopy, and/or varices seen on computerized tomography (CT) scan or ultrasound, and or splenomegaly with no other explanation, and/or ascites with no other explanation, and/or hepatic vein wedge pressure greater than 12 mm Hg) IPVDs diagnosed on contrast echocardiography (CE) exhaled nitric oxide level greater than 12.6 ppb

Exclusion Criteria:

Significant pre-existing respiratory disease (in these cases, the diagnosis of HPS or pre-HPS is uncertain, given that observed elevations in AaDO2 may be from underlying lung disease):

forced expiratory volume in 1 second (FEV1) less than 70 percent of predicted forced vital capacity (FVC) less than 70 percent of predicted FEV1/FVC less than 0.7 inability to perform pulmonary function tests (for the same reasons, it is important to document normal underlying lung function) echocardiographic estimated right ventricular systolic pressure 50 mm Hg or right heart catheterization mean pulmonary artery pressure greater than 25 mm Hg (pulmonary hypertension may result in progressive hypoxemia due to intracardiac shunt or right ventricular failure) inadequate echocardiographic window to allow for accurate transthoracic contrast (bubble) echocardiogram (CE) (this is the test used to identify IPVDs) antibiotic use within the last 1 month (this is the intervention being tested) (note that all subjects will be under the concurrent care of a gastroenterologist or hepatologist, and some patients may accordingly be on prophylactic antibiotic therapy for prior SBP or variceal hemorrhage; these patients will be excluded) (20 percent expected rate of exclusion due to this criterion) current use of exogenous nitrates (may increase exhaled NO levels) norfloxacin intolerance (norfloxacin administration is the study intervention): allergy or intolerance to norfloxacin or other fluoroquinolones history of tendon rupture associated with norfloxacin or other fluoroquinolones glucose 6-phosphate dehydrogenase deficiency (possibility of hemolytic reactions with norfloxacin) known prolongation of the QTc interval to a duration that is > 50% of the R-R interval, subjects taking QTc-interval prolonging drugs, subjects with uncorrected hypokalemia, clinically significant bradyarrhythmias or acute myocardial ischemia (norfloxacin may worsen this) pregnancy (norfloxacin contraindicated) age less than 18 or greater than 70 expected death/transplantation within 3 mo (treating physician's discretion) lactose intolerance (placebo contains lactose) Smoking within the last 1 month

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00362752

Locations
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Sponsors and Collaborators
St. Michael's Hospital, Toronto
University of Toronto
Investigators
Principal Investigator: Marie Faughnan, MD MSc FRCPC St. Michael's Hospital, Toronto Canada; University of Toronto
  More Information

No publications provided

Responsible Party: Dr. Marie Faughnan, St. Michael's Hospital
ClinicalTrials.gov Identifier: NCT00362752     History of Changes
Other Study ID Numbers: 02-120
Study First Received: August 8, 2006
Last Updated: January 26, 2010
Health Authority: Canada: Health Canada

Keywords provided by St. Michael's Hospital, Toronto:
norfloxacin
hepatopulmonary syndrome

Additional relevant MeSH terms:
Hepatopulmonary Syndrome
Syndrome
Digestive System Diseases
Disease
Liver Diseases
Lung Diseases
Pathologic Processes
Respiratory Tract Diseases
Norfloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014