A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome
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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 |
- - Primary endpoint: A-a gradient [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- 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 |
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| Canada, Ontario | |
| St. Michael's Hospital | |
| Toronto, Ontario, Canada, M5B 1W8 | |
| 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 Liver Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Norfloxacin Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Nucleic Acid Synthesis Inhibitors Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 22, 2013