The investigators propose the first prospective, double blind, randomized controlled trial of treatment for pulmonary arterial hypertension (PAH) related to underlying portal hypertension. Specifically the investigators will evaluate the potential efficacy and safety of sildenafil (Revatio) in a 16 week blinded, multicentre study.
PAH is a recognized complication of portal hypertension - termed portal-pulmonary hypertension (PPHTN). In the World Health Organization (WHO) classification PPHTN is categorized as a WHO group 1 condition. This categorization is appropriate as PPHTN shares similar pathological features and clinical presentation and as idiopathic (primary) pulmonary arterial hypertension (PAH). Advances in oral therapies in PAH (idiopathic, connective tissue disease, congenital heart disease) has deferred the need for parenteral therapies, lung transplantation and led to improvements in functional capacity, quality of life and survival. However unlike other forms of PAH, treatment options have not been formally evaluated for PPHTN and there are no approved medical therapies. Patients are unable to pay for medications. Consequently patients continue to endure the natural progression of PAH - a state characterized by progressive right heart failure, disability and death. Furthermore the unacceptable mortality associated with liver transplantation in the presence of hemodynamically significant PAH, leaves them with no therapeutic options. Therefore, new treatment options need to be systematically evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
12
20 mg Revatio (sildenafil citrate) three times a day
Placebo identical to Revatio (sildenafil citrate) three times a day
Lawson Health Research Institute (London Health Sciences Centre Research Inc.)
London, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Canada
Change from baseline in PVR after 16 weeks of treatment
Time frame: 16 weeks
For patients with a PVR>450 dynes/sec/cm5 at baseline, number of patients who have PVR below 350 dynes/sec/cm5 after 16 weeks of study drug will be determined
Time frame: 16 weeks
Hospitalizations
Time frame: 16 weeks
Death
Time frame: 16 weeks
Complications of liver disease
Time frame: 16 weeks
MELD score
Time frame: 16 weeks
Renal dysfunction
Time frame: 16 weeks
Desaturation
Time frame: 16 weeks
Change in 6MWD from baseline
Time frame: 16 weeks
Change in baseline WHO functional class
Time frame: 16 weeks
Change in Brain Natruretic Peptide (BNP) from baseline
Time frame: 16 weeks
Change from baseline in CAMPHOR and SF-36 measures of quality of life
Time frame: 16 weeks
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