Empagliflozin as a Novel Therapy in Refractory Ascites

Empagliflozin in the Management of Cirrhosis-related Refractory Ascites: a Randomized Controlled Trial

The aim of the present study is to investigate the safety, efficacy and cost-effectiveness of empagliflozin, a sodium glucose transporter 2 inhibitor, as an add on therapy to the standard care for refractory ascites in patients with liver cirrhosis

Study Overview

• Status: Completed
• Conditions: Ascites Hepatic
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Diuretics

Detailed Description

Midodrine will be added if the blood pressure less than 100/70 mmHg during the follow up period (start by dose 5 mg three times daily and up titrate the dose according to the blood pressure monitoring to maximum dose 12.5 mg three times daily.

• Treatment of empagliflozin will be stopped if patient developed any of the following (attack of symptomatic hypoglycemia, hypotention not responding vasopresser agent, complicated urinary tract infection or attack of diabetic ketoascidosis) .
• The dose of diuretics will be reduced if marked weight reduction occurred (more than 0.5 kilogram/day in patient with ascites only or more than 1 killogram /day in patients with ascites and lower limb edema).
• The diuretics will be stopped temporally if any of the following (renal impairment, attack of hepatic encephalopathy, severe electrolyte imbalance) and permanently if the urine sodium < 30 mEq per day or there are intolerable side effects.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21131
    • Alexandria University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Age older than 18 years old. 2. Ability to give a written informed consent. 3. Decompensated liver cirrhosis complicated with ascites. 4. Diagnosis of refractory ascites has made 3 months before informed consent which defined as one of the following(6)

  1. Ascites that cannot be mobilized or the early recurrence of which cannot be prevented despite moderate salt restriction and maximum dose of diuretics ( furosemide 160 mg or equivalent and spironolactone 400mg)
  2. Ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of the development of diuretic-induced complications that preclude the use of an effective diuretic dosage.

Exclusion Criteria:

• 1. History of any attack of hypoglycemia (defined as serum glucose less than 70 mg/dl) either symptomatic or a symptomatic.

  2. Blood pressure below 90/60 or History of Hypotension requiring high dose of vasopressor therapy (more than 15mg midodrine /day) 3. Patients who receive non-selective B-blockers. 4. History of recurrent urinary tract infection defined as more than 2 infections in last 6 months 5. Pregnancy and breast feeding 6. History of hypersensitivity to any SGLT2 inhibitor 7. Presence of hepatocellular carcinoma or any other malignancy. 8. eGFR below 30 ml/min using Modification of Diet in Renal Disease study (MDRD) 9. Patients with history of diabetes mellitus complicated with diabetic ketoacidois (DKA) or patients have any risk factors for DKA 10. History of alcohol intake 11. Modified Child-Pugh score 12 or more.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin group	Drug: Empagliflozin 10 MG; once daily empagliflozin 10mg+/- diuretics; Drug: Diuretics; diuretics as clinically indicated
Active Comparator: standard treatment only group	Drug: Diuretics; diuretics as clinically indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
No need for paracentecis	3 months

Collaborators and Investigators

• Sponsor: Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Actual): November 12, 2022
• Study Completion (Actual): November 12, 2022

Study Registration Dates

• First Submitted: June 18, 2022
• First Submitted That Met QC Criteria: June 18, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 26, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin; Diuretics
• Other Study ID Numbers: 0305418

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes