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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-03

Study Completion Date

2022-05-19

Brief Summary

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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.

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Detailed Description

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Conditions

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Cirrhosis Ascites Hepatic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group A (Dapaglifozin)

Group A will receive oral Dapaglifozin (10 mg/day) along with standard medical therapy for 6 months

Group Type ACTIVE_COMPARATOR

Dapagliflozin (10Mg Tab) along with standard medical therapy

Intervention Type 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

Group B (Placebo)

Group B will receive placebo of Dapaglifozin along with standard medical therapy for 6 months

Group Type PLACEBO_COMPARATOR

Placebo of dapaglifozin along with standard medical therapy

Intervention Type 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.

Interventions

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Dapagliflozin (10Mg Tab) along with standard medical therapy

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

Intervention Type DRUG

Placebo of dapaglifozin along with standard medical therapy

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age 18-70 years
2. Cirrhosis as determined by clinical findings, hemogram and liver function tests, endoscopic findings and imaging
3. Recurrent ascites: Recurrent ascites will be defined as tense ascites recurring at least thrice within the last 1-year despite optimal standard medical treatment including large volume paracentesis and diuretics

Exclusion Criteria

1. Presence of chronic kidney disease as defined by an estimated glomerular filtration rate of \<60 ml/min for more than 3 months. The MDRD-6 equation will be used for estimating GFR.
2. Portal vein thrombosis
3. Hepatocellular carcinoma.
4. Gastrointestinal bleed in the preceding 2-weeks
5. Overt hepatic encephalopathy in the preceding 1-month
6. Documented hypoglycemia in the preceding 1-month
7. Serum sodium \< 125 meq/l
8. History of skeletal fracture in the preceding year or any past history of fragility fracture
9. History of peripheral vascular disease
10. Acute kidney injury as defined by the International Club of Ascites criteria
11. Infection within 1-month preceding the study
12. Anatomic urologic defects that predispose to urinary tract infection
13. Mixed ascites (additional etiology of ascites apart from portal hypertension)
14. Any severe extra hepatic condition including respiratory and cardiac failure
15. Acute-on-chronic liver failure as per the APASL or CANONIC criteria
16. Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers
17. Patients opting for liver transplant or TIPS
18. Refusal to give consent

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No