Clinical Trial: A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study of Norfloxacin for Hepatopulmonary Syndrome

Brief Summary:

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.


Detailed Summary:

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 ?

This is in order to enable accurate sample size estimations for a future large randomized-controlled trial of norfloxacin administration in the treatment of HPS and pre-HPS.

Significance:

HPS and pre-HPS is a disease that carries a high morbidity and an alarmingly high mortality. Orthotopic liver transplantation (OLT) is the only effective treatment, and in itself threatens a significant operative mortality in these patients.

A growing body of literature has built an elegant and compelling case for the role of gut bacterial translocation and secondary pulmonary nitric oxide (NO) overproduction in the pathophysiology of HPS.

A sophisticated rat model and a case report in a human subject have supported the potential for norfloxacin, a widely available, cheap and non-toxic antibiotic, to mitigate these effects and improve oxygenation, which is the most important contributor to both morbidity and mortality in HPS.

Given the dismal prognosis of this disease, the biological plausibility of the hypothesis, and the minimal foreseeable deleterious
Sponsor: St. Michael's Hospital, Toronto

Current Primary Outcome: - Primary endpoint: A-a gradient [ Time Frame: 4 weeks ]

Original Primary Outcome: - Primary endpoint: A-a gradient

Current Secondary Outcome:

  • paO2, [ Time Frame: 4 weeks ]
  • exhaled NO [ Time Frame: 4 weeks ]
  • DLCO [ Time Frame: 4 weeks ]
  • 6MWD [ Time Frame: 4 weeks ]
  • CO [ Time Frame: 4 weeks ]
  • TPR [ Time Frame: 4 weeks ]
  • PAP (on echocardiogram) [ Time Frame: 4 weeks ]
  • endotoxin levels [ Time Frame: 4 weeks ]
  • ET-1 levels [ Time Frame: 4 weeks ]
  • MELD score [ Time Frame: 4 weeks ]
  • bilirubin and INR [ Time Frame: 4 weeks ]
  • BDI [ Time Frame: 4 weeks ]
  • TDI [ Time Frame: 4 weeks ]
  • CRQ [ Time Frame: 4 weeks ]


Original Secondary Outcome:

  • Secondary endpoints: (as above) pO2,
  • exhaled NO,
  • DLCO,
  • 6MWD,
  • CO,
  • TPR,
  • PAP (on echocardiogram),
  • endotoxin levels,
  • ET-1 levels,
  • MELD score (based on creatinine,
  • bilirubin and INR),
  • BDI,
  • TDI,
  • CRQ


Information By: St. Michael's Hospital, Toronto

Dates:
Date Received: August 8, 2006
Date Started: October 2006
Date Completion:
Last Updated: December 6, 2016
Last Verified: December 2016