Sodium-glucose Linked Transporter 2 (SGLT-2) Inhibitors in Recurrent Ascites: a Pilot RCT

Sponsor
Post Graduate Institute of Medical Education and Research, Chandigarh
Study ID
NCT05014594
Phase
PHASE2
Status
Unknown

Conditions

  • Ascites Hepatic
  • Cirrhosis

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin (10Mg Tab) along with standard medical therapy — DRUG
    Oral Dapaglifozin (10 mg/day) along with standard medical therapy will be given to Group A while a placebo of dapaglifozin along with standard medical therapy will be used in Group B
  • Placebo of dapaglifozin along with standard medical therapy — DRUG
    Standard medical therapy will include dietary restriction of sodium, treatment with diuretics, repeated LVP as needed and other supportive care. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines.

Study Details

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.

Key Dates

Start date
Sep 3, 2021
Status verified
Sep 2021
Primary completion
May 19, 2022
Completion
May 19, 2022

Study Design

Enrollment
44 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Group A (Dapaglifozin)
    Group A will receive oral Dapaglifozin (10 mg/day) along with standard medical therapy for 6 months
  • Placebo Comparator: Group B (Placebo)
    Group B will receive placebo of Dapaglifozin along with standard medical therapy for 6 months

Primary Outcome Measure

control of ascites at 6-months [ Time Frame: 6 months ]

Central Contacts

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