Refractory ascites is a serious complication of cirrhotic portal hypertension and is associated with considerable morbidity, increasing health costs, decreasing quality of life and eventually death or increased risk of death after orthotopic liver transplant (OLT). Repeated large volume paracentesis (LVP), or total paracentesis (TP), are equally safe and efficacious in removing ascites, but are limited by frequent recurrence of tense ascites and failure to improve survival. Surgical portacaval shunts (PCS) decompress hepatic sinusoids and relieve ascites, but are associated with considerable morbidity and mortality. Trans-jugular intrahepatic portasystemic shunts relieve portal hyper-tension like side-to-side PCS, but avoid the risks of anesthesia and surgery. Initial studies suggest that TIPS may be an effective treatment of refractory ascites, but controlled data are lacking. The North American Study of Treatment for Refractory Ascites (NASTRA) is a multicenter prospective randomized clinical trial which will test the hypothesis that TIPS is more effective than """"""""standard therapy (TP/Na restriction /diuretics)"""""""" for refractory ascites. The participating centers include six university-based tertiary care institutions with established hepatology and liver transplant programs. Patients will be randomized to standard therapy or experimental therapy (TIPS + standard therapy). Since the principal objective is to maintain an ascites free state, the primary endpoint will be the hazard of recurrence of tense ascites requiring therapeutic paracentesis. Secondary endpoints will include survival, frequency of complications of cirrhosis, diuretic dose requirement, changes in nutritional status, quality of life, frequency of mitigation of the need for OLT and the frequency and spectrum of complications in both study arms. The economic impact of the two treatment strategies will also be compared with a focus on health-care resource utilization. Finally, the effects of TIPS on portal, systemic and renal hemodynamics, renal function and Na homeostasis will be measured. The frequency and severity of recurrent portal hypertension due to TIPS stenosis will be defined and its effects on the pathophysiologic abnormalities in these patients characterized. The investigators indicate that considerable progress has already been made and the proposed study is likely to both improve the standard-of-care as well as provide new or fresh impetus to several areas of research in liver disease. It is anticipated that 150 patients will be enrolled for this trial which will take five years for completion.
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