Role of Midodrine and Tolvaptan in Patients With Cirrhosis With Refractory or Recurrent Ascites
Status:
Completed
Trial end date:
2016-03-01
Target enrollment:
Participant gender:
Summary
The development of ascites in the natural history of cirrhosis heralds a worsening of the
prognosis to 50% survival at 2 years, and this deteriorates to 30-50% at 1 year when the
ascites becomes refractory to medical therapy. Hemodynamic alterations and their relation to
neurohumoral systems are essential in pathophysiology of ascites formation. The theory that
best explain the ascites formation and sodium retention in cirrhotics is portal hypertension
leading to splanchnic arterial vasodilatation leading to underfilling of arterial circulation
which is sensed by the arterial and the cardiopulmonary receptors leading to sympathetic
nervous system activation and activation of the anti-natriuretic factors (RAAS and arginine
vasopressin), resulting in sodium and water retention. The therapeutic options available for
patients with refractory ascites are serial therapeutic paracentesis, liver transplantation
and transjugular intrahepatic portosystemic shunts.Vasopressin V2 receptor antagonists
antagonize the antidiuretic effects of vasopressin at the V2 receptor located in the renal
collecting duct, they increase free water clearance, and thus may be helpful in mobilizing
excess water in conditions associated with water retention including cirrhosis. The use of V2
receptor antagonists in cirrhosis with ascites has been shown to be safe and efficacious.
Midodrine, an alpha adreno receptor agonist by causing splanchnic vasoconstriction has been
used in hepatorenal syndrome (HRS) and for control of ascites in patients with refractory or
recurrent ascites. It is possible that vasoconstrictors and aquaretics (V2 receptor
antagonists) by acting at different sites in combination may reverse some of the pathogenic
events that results in refractory or recurrent ascites.There are no reports on the use of
combination of midodrine and tolvaptan in the patients with cirrhosis with ascites.
Therefore, we plan to study the role of midodrine, tolvaptan and their combination on
systemic hemodynamics, renal functions and control of ascites in patients with cirrhosis and
refractory or recurrent ascites.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research