Sodium-glucose Linked Transporter 2 (SGLT-2) Inhibitors in Recurrent Ascites: a Pilot RCT
Status:
Recruiting
Trial end date:
2022-05-19
Target enrollment:
Participant gender:
Summary
The development of ascites is a landmark event in the natural history of cirrhosis and
signifies a grim prognosis. Portal hypertension and splanchnic arterial vasodilatation are
the major contributors in the development of ascites. Vasodilatation with the consequential
decrease in effective circulating volume leads to the activation of sympathetic nervous
system and renin angiotensin aldosterone system (RAAS), leading to antinatriuretic effects
and retention of sodium and water. This results in the formation of ascites. Management of
ascites primarily consists of salt restrictrion and diuretics. Liver transplant is the
ultimate panacea.
Dapaglifozin, a Sodium glucose linked transporter-2(SGLT-2) inhibitor, is a part of the
routine armamentarium for treatment of patients with Diabetes Mellitus type-2. Its safety is
well established in non-diabetic patients too where it has been shown to improve
cardiovascular outcomes. The risk of hypoglycemia is negligible as its action is independent
of insulin. By virtue of its natriuretic effect, it has been shown to reduce hospitalisations
in patients with heart failure irrespective of the presence of diabetes. We hypothesise that
a similar natriuretic effect may help in suppressing the renin-angiotensin axis with improved
mobilization of ascites in patients with cirrhosis. Pharmacokinetic data on the use of
Dapaglifozin suggest that there is no need for dose modification in cirrhosis. The AUC and
Cmax for Dapaglifozin in Child Pugh C cirrhosis is 67% and 40%, respectively. In a recent
small case series, SGLT-2 inhibitors including dapaglifozin led to improvement in fluid
retention and serum sodium, without acute kidney injury or encephalopathy, in patients with
cirrhosis. However, SGLT-2 inhibitors have not been evaluated in randomized controlled
trials. In this pilot study, we plan to evaluate the efficacy and safety of dapaglifozin in
cirrhotics patients with recurrent ascites.
Phase:
Phase 2
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research