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

NCT05014594 | Unknown Phase 2

• 1 other identifier: Dapa recurrent ascites
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cirrhosis; Ascites Hepatic

Outcome Measures

Primary Outcomes (1)

• control of ascites at 6-months

  Control of ascites will be defined as follows- * Complete response will be total absence of ascites. * Partial response as presence of ascites not requiring paracentesis * Non response will be defined as persistence of severe ascites requiring paracentesis.

  6 months

Secondary Outcomes (20)

• Change in eGFR measured by MDRD-6 at 3 months and 6 months

  6 months

• Change in urine output at 2-weeks, 3-months and 6-months

  6-months

• Change in serum sodium (mEq/l) at 2-weeks, 3-months and 6 months

  6 months

• Change in 24-hours urinary sodium (mEq) at 2 weeks, 3 months and 6 months

  6 months

• Change in HbA1c at 3 and 6 months

  6 months

Study Arms (2)

Group A (Dapaglifozin)

ACTIVE COMPARATOR

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

Drug: Dapagliflozin (10Mg Tab) along with standard medical therapy

Group B (Placebo)

PLACEBO COMPARATOR

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

Drug: Placebo of dapaglifozin along with standard medical therapy

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

Group A (Dapaglifozin)

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.

Group B (Placebo)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years
• Cirrhosis as determined by clinical findings, hemogram and liver function tests, endoscopic findings and imaging
• 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

You may not qualify if:

• 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.
• Portal vein thrombosis
• Hepatocellular carcinoma.
• Gastrointestinal bleed in the preceding 2-weeks
• Overt hepatic encephalopathy in the preceding 1-month
• Documented hypoglycemia in the preceding 1-month
• Serum sodium \< 125 meq/l
• History of skeletal fracture in the preceding year or any past history of fragility fracture
• History of peripheral vascular disease
• Acute kidney injury as defined by the International Club of Ascites criteria
• Infection within 1-month preceding the study
• Anatomic urologic defects that predispose to urinary tract infection
• Mixed ascites (additional etiology of ascites apart from portal hypertension)
• Any severe extra hepatic condition including respiratory and cardiac failure
• Acute-on-chronic liver failure as per the APASL or CANONIC criteria

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Dept of Hepatology, PGIMER

Chandigarh, 160012, India

RECRUITING

Related Publications (1)

• Singh V, De A, Aggrawal R, Singh A, Charak S, Bhagat N. Safety and Efficacy of Dapagliflozin in Recurrent Ascites: A Pilot Study. Dig Dis Sci. 2025 Feb;70(2):835-842. doi: 10.1007/s10620-024-08667-4. Epub 2024 Oct 9.

  PMID: 39384712 DERIVED

MeSH Terms

Conditions

Fibrosis

Interventions

dapagliflozin; Tablets

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Virendra Singh, MD,DM,FASGE

CONTACT

0172-275-6338; virendrasingh100@hotmail.com

Rishav Aggarwal, MBBS

CONTACT

9914032190; rishavaggarwal90@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head, Department of Hepatology

Study Record Dates

• First Submitted: August 14, 2021
• First Posted: August 20, 2021
• Study Start: September 3, 2021
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: September 5, 2021

Record last verified: 2021-09

Locations

IN (1)