Clinical Trial: Prevention of Decompensation in Liver Cirrhosis
Study Status: Not yet recruiting
Recruit Status: Unknown status
Study Type: Interventional
Official Title: Losartan in the Prevention of Sodium Retention and Ascites in Liver Cirrhosis – a Prospective Randomized Long-Term Study
Brief Summary: The purpose of this study is to determine whether losartan, an angiotensin II blocker prevents the sodium retention in patients with liver cirrhosis and by that reduces the fluid retention. Moreover is the purpose to asses whether losartan is antifibrotic.
Detailed Summary:
Patients with cirrhosis tend to retain sodium and water leading to the development of ascites, which in the terminal stage of decompensation cannot be eliminated despite the use of massive diuretic treatment. These decompensated patients have a very high mortality of 50 % within 3 years and morbidity, and until now no symptomatic treatment has been able to improve the prognosis.
It has been hypothesized that ascites and edema develop first due to renal sodium retention secondary to increased activity of hormones like angiotensin II and aldosterone, which may be stimulated by reduced arterial filling caused by systemic vasodilatation, and secondly due to liver fibrosis which may cause lymphatic overflow and formation of ascites.
Decreased central volume filling is believed to stimulate baroreceptors with activation of the renin-angiotensin-aldosterone system, the sympathetic nervous system and arginine vasopressin .
In cirrhotic patients systemic vasodilatation with hypotension, tachycardia, increased cardiac output and increased plasma volume has been thought to be caused by increased levels of vasodilating substances like nitric oxide (NO), but blocking NO synthesis using N(G)-monomethyl-L-arginine-acetate (L-NMMA) did not favorably influence renal sodium excretion, probably due to an important role of NOS in renal sodium handling .
It is evident that the pathophysiology of the development of excessive sodium and water retention in cirrhotic patients is insufficiently elucidated, and that an increased knowledge in this field may improve the therapeutic possibilities. Patients with cirrhosis without ascites have normal or increased glomerular filtration rate (GFR) and normal or suppressed plasma levels of renin, angiotensin
Sponsor: Odense University Hospital
Current Primary Outcome: Death
Original Primary Outcome: Same as current
Current Secondary Outcome:
- varices
- need for therapeutic ascites drainage
- gastrointestinal bleeding episodes
Original Secondary Outcome: Same as current
Information By: Odense University Hospital
Dates:
Date Received: October 12, 2005
Date Started: September 2005
Date Completion: September 2011
Last Updated: October 13, 2005
Last Verified: October 2005
