A study to evaluate the efficacy of SGLT2 inhibitor (Empagliflozin) as an adjunctive to SoC therapy in the management of refractory ascites in Cirrhosis
Trial Snapshot
- Phase
- Phase 3 4
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Number of therapeutic paracenteses per patient and total paracentesis volume during 12 weeks
Study Overview
Brief Summary
Ascites is the most common complication of cirrhosis, continued up to 60% of the patients with a 10 years of diagnosis. Among these 5 to 10% develop refractory ascites, defined as ascites that cannot be mobilized or recur rapidly despite dietary sodium restriction and maximal diuretic therapy. If there is a worse prognosis with median survival of less than 6 months. Current treatment plan diuretics include large-volume paracentesis, TIPS, vasoconstrictor therapy albumin infusions and diuretics. However these approaches of limitation such as procedure complication, recurrence of ascites and cost issues. Sodium glucose Co. transporter 2 (SGLT-2) inhibitors are relatively new class of antihyperglycemic agents have been shown to be renal protective and cardioprotective benefits beyond glycemic control. They are not benefiting glucose and sodium reabsorption in the proximal and ventricular producing osmotic diuresis natriuresis independent of aldosterone. This mechanism evaluation and patient with cirrhosis and ascites, with activation of the renin-angiotensin-aldosterone system aortic distance may have sclerosing pathophysiology.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- None
Eligibility Criteria
- Ages
- 18.00 Year(s) to 70.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Cirrhosis (clinical, imaging, and/or histological) with refractory ascites (due to portal hypertension).
- •Subjects who are willing and able to comply with treatment plan, laboratory tests.
- •Subjects who are willing to provide a written informed consent.
Exclusion Criteria
- •Previous history of documented hypoglycemia (in the preceding 1 month).
- •Previous history of repeated urinary tract infection (UTI) (more than 2 infections within 6 months),.
- •Pregnant or lactating females,.
- •Previous history of hypersensitivity to any SGLT2 inhibitor.
- •Serum sodium < 125 meq/L.
- •History of peripheral vascular disease (ulcer/gangrene/amputation).
- •Severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis requirement.
- •Active alcohol use with last alcohol intake 1 month back.
- •GI bleeding in the previous 1 month.
- •Overt HE in the previous 1 month.
- •Treatment with drugs with known effects on systemic and renal hemodynamics within 7 days of inclusion, except beta blockers.
- •Previous history of diabetic ketoacidosis,.
- •Child–Pugh score of 12 or more.
- •Hepatocellular carcinoma.
- •Portal Vein Thrombosis.
- •Mixed ascites (etiology of ascites other than portal hypertension).
- •Patients opting for liver transplant or TIPS.
- •H/o pancreatitis/pancreatic surgery.
Outcomes
Primary Outcomes
Number of therapeutic paracenteses per patient and total paracentesis volume during 12 weeks
Time Frame: 12 weeks
Secondary Outcomes
- Change in serum sodium and spot urinary sodium(Weeks 4, 8 and 12)
- Change in abdominal girth (cm) from baseline(Weeks 4, 8 and 12)
- Change in body weight (kg)(Weeks 4, 8 and 12)
- Change in eGFR from baseline(Weeks 4, 8 and 12)
- Change in HbA1c(12 weeks)
- Change in prognostic scores (CTP, MELD Na) from baseline(Weeks 4, 8 and 12)
- Incidence of AKI (as per KDIGO), serious adverse events (including SGLT2-i related AEs)(12 weeks)
- Frequency of hepatic encephalopathy(12 weeks)
- Frequency of SBP, UTI and other infections(12 weeks)
Investigators
Dr Varun Mehta
DMCH Ludhiana