Refractory ascites is seen in 5-10% of patients with cirrhosis.Decompensated cirrhosis with refractory ascites has a mortality rate of around 40% in a year and a median survival of 6 months.Portal hypertension and splanchnic vasodilation are major factors in the development of ascites.The treatment of refractory ascites involves salt restriction, diuretics, large volume paracentesis (LVP), transjugular Intrahepatic Portosystemic shunt (TIPS) and Liver Transplantation (LT). Currently the only curative treatment is LT. However, LT is limited due to organ shortage and high cost. Long-term human albumin (HA) administration in patients with uncomplicated and refractory ascites, has shown to improve survival or delay the complications of cirrhosis. Midodrine, an oral α1- adrenergic agonist has been used in refractory ascites with variable results. However, there is no study on the use of long term Midodrine and HA in patients with refractory ascites. Therefore, we plan to study the effect of long term midodrine and HA in patients with refractory ascites.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
114
Human albumin will be administered by intravenous infusion at a dose of 1.5 gm/kg/week for 2 weeks followed by HA 40 grams every 7days
Oral Midodrine will be given at a dose of 7.5 mg three times in a day
SMT will include nutritional support, rifaximin, lactulose or lactitol, diuretics, SBP prophylaxis with norfloxacin, restriction of sodium, multivitamins, and other supportive measures as deemed necessary. LVP will be done as needed. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines.
Number of patients with control of ascites at 1 year
Control of ascites will be defined as- * 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.
Time frame: 1 year
Change in estimated glomerular filtration rate (eGFR) measured by modified diet in renal disease 6 (MDRD6) formula at 3 months intervals
eGFR will be measured using MDRD6 formula
Time frame: 1 year
Changes in concentration of albumin at 3 months intervals
Change in concentration of serum albumin (g/dl)
Time frame: 1 year
Change in model for end stage liver disease (MELD) score
Change in MELD score. The MELD score incorporates the variables of serum bilirubin, creatinine and Internation Normalised Ratio (INR). Higher MELD score indicates worse prognosis
Time frame: 1 year
Change in mean arterial pressure at 3 months interval
Change in mean arterial pressure (mm of Hg) will be noted
Time frame: 1 year
Changes in serum and 24- hour urine sodium
Serum and urine sodium concentration will be measured in meq/L
Time frame: 1 year
Incidence of spontaneous bacterial peritonitis (SBP) and other infections
The diagnosis of SBP will be based on neutrophil count in ascitic fluid of \>250/mm3 as determined by microscopy and positive ascitic fluid culture or \>250 /mm3 with negative culture called as culture negative neutrocytic ascites.20 Other infections will be diagnosed as per CDC criteria.
Time frame: 1 year
Number of patients who develop paracentesis induced circulatory dysfunction (PICD)
PICD will be defined as an increase in plasma renin activity (PRA) of \>50% of the pre-treatment value to a level \> 4ng/ml/hr on 6th day after paracentesis
Time frame: 1 year
Number of patients who develop hyponatremia
Hyponatremia will be defined using serum sodium concentrations of \<130meq/L.
Time frame: 1 year
Change in Child-Turcotte-Pugh (CTP) score
Change in CTP score. The CTP score incorporates the variables of serum bilirubin, albumin, prothrombin time-INR, grade of ascites and hepatic encephalopathy. The score ranges from 5-15 and a higher score portends a worse prognosis
Time frame: 1 year
Number of patients who develop hypokalemia
Hypokalemia will be defined using serum potassium levels \<3 meq/L
Time frame: 1 year
Number of patients who develop hyperkalemia
hyperkalemia will be defined using serum potassium levels \>6 meq/L
Time frame: 1 year
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