A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- - Primary endpoint: A-a gradient
研究概览
简要总结
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.
详细描述
Research Question:
This is a pilot study; the fundamental research question is:
Does norfloxacin administration reduce Alveolar-arterial oxygen gradient (AaDO2) in patients with HPS and pre-HPS?
However, for this particular pilot study, the research question is:
What is the magnitude and standard deviation of the change in A-a gradient with norfloxacin treatment in subjects with HPS and pre-HPS ?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Norfloxacin 400 mg bid
干预措施: Norfloxacin (Drug)
结局指标
主要结局
- Primary endpoint: A-a gradient
时间窗: 4 weeks
次要结局
- paO2,(4 weeks)
- endotoxin levels(4 weeks)
- DLCO(4 weeks)
- CO(4 weeks)
- TDI(4 weeks)
- exhaled NO(4 weeks)
- ET-1 levels(4 weeks)
- TPR(4 weeks)
- BDI(4 weeks)
- CRQ(4 weeks)
- 6MWD(4 weeks)
- PAP (on echocardiogram)(4 weeks)
- MELD score(4 weeks)
- bilirubin and INR(4 weeks)
研究者
Marie Faughnan
Dr.
Unity Health Toronto