Empagliflozin in Diuretic Refractory Ascites
Condition: Liver Cirrhosis; Cirrhosis; Ascites; Ascites Hepatic; Sodium-Glucose Transporter 2 Inhibitors
MeSH terms: Liver Cirrhosis; Fibrosis; Ascites
Study type: Interventional
Phase: Phase 1

Summary: 
      Ascites is the most frequent complication of liver cirrhosis and results in increased
      morbidity and mortality but current medical management options are limited. Here, the
      investigators will conduct an interventional single-arm pilot clinical trial toevaluate the
      feasibility of empagliflozin in managing diuretic-resistant ascites in patients with
      decompensated cirrhosis. This single site, open label pilot study will enroll participants
      with decompensated cirrhosis at a single site. Participants will receive empagliflozin 10mg
      oral tablets once daily for 12 weeks with monitoring for safety and adverse events.
    

Detailed description: 
      Pharmacologic options for the management of ascites are limited to diuretics only. Each year
      approximately 10% of patients with cirrhosis develop diuretic-resistant ascites,
      necessitating the use of more invasive procedures such a paracentesis, transjugular
      intrahepatic portosystemic shunting (TIPS), and transplantation; each modality is associated
      with significant risks and limitations. Patients treated with diuretics may also develop
      complications such as acute kidney injury, encephalopathy, muscle cramping, or hyponatremia,
      limiting optimal dosages of these medications and hence, resulting in inadequate control of
      fluid retention. Thus, ascites that is resistant to our current therapies is an important
      unmet medical need.

      Recently, SGLT2-Is have been shown to reduce heart failure hospitalizations and
      cardiovascular death in patients with and without diabetes in landmark, large-scale clinical
      trials. Empagliflozin improved heart failure outcomes without altering hemoglobin A1c or
      increasing risk of hypoglycemia in individuals without diabetes, suggesting that SGLT2-Is may
      act through a neurohormonal mechanism independent of blood glucose changes. Because cirrhosis
      and heart failure are disorders with a common pathophysiology of decreased effective arterial
      blood volume with resultant stimulation of the renin-angiotensin-aldosterone system (RAAS),
      sympathetic nervous system, and total body fluid overload, the investigators hypothesize that
      SGLT2-Is may be effective in the management of ascites. Multiple lines of evidence suggest
      SGLT2-Is may have a beneficial role in chronic liver disease. Several case reports of
      patients with cirrhosis and diuretic-resistant ascites have found that SGLT2-I treatment was
      associated with near resolution of ascites and pedal edema. SGLT2-I treatment has also
      demonstrated improved hepatic function, reduction of fibrosis and normalization of liver
      enzymes in non-alcoholic fatty liver disease (NAFLD).Although SGLT2-I are partially cleared
      by the liver, empagliflozin is well tolerated in patients with cirrhosis. Thus, the
      investigators initiated a feasibility study to test the hypothesis that the SGLT2-I,
      empagliflozin, will decrease ascites by attenuating maladaptive neurohormonal and
      inflammatory responses in cirrhosis.
    

Intervention name(s): Empagliflozin 10 MG
Intervention type(s): Drug
Intervention description(s): empagliflozin 10mg PO once daily
Intervention MeSH terms: Empagliflozin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: diuretic refractory; diuretic resistant; empagliflozin