Midodrine and Albumin in Patients With Refractory Ascites

Refractory Ascites Clinical Trial

Official title:

Midodrine and Albumin in Patients With Refractory Ascites. A Randomised Controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04621617
• Other study ID #: IEC-06/2020-1691
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 2020
• Est. completion date: April 2022

Study information

• Verified date: November 2020
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Virendra Singh, MD, DM
• Phone: 0172-275-6338
• Email: virendrasingh100[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 114
• Est. completion date: April 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and 80 years

2. Refractory ascites in cirrhosis of any etiology

Exclusion Criteria:

1. Mixed ascites: cirrhosis plus another cause of ascites

2. Gastrointestinal bleed within 7 days of enrolment.

3. Presence of hepatorenal syndrome

4. Hepatic encephalopathy grade 2 or higher

5. Infection within 1 month preceding the study

6. Cardiovascular disease (ejection fraction < 35% or abnormal ECG) or arterial hypertension (BP > 140/90 mm of Hg)

7. Abnormal urine analysis with proteinuria > 500 mg/24 hour or 50 red blood cells/high power field, or granular casts or ultrasonographic evidence of intrinsic renal disease

8. Presence of hepatocellular carcinoma or portal vein thrombosis

9. Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers

10. Patient not willing for study.

11. Patient opting for liver transplantation/ transjugular intrahepatic portosystemic shunt

Related Conditions & MeSH terms

• Ascites
• Refractory Ascites

Intervention

Drug:
• Albumin
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
• Midodrine
Oral Midodrine will be given at a dose of 7.5 mg three times in a day
• Standard medical therapy (SMT)
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 year
Secondary	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	1 year
Secondary	Changes in concentration of albumin at 3 months intervals	Change in concentration of serum albumin (g/dl)	1 year
Secondary	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	1 year
Secondary	Change in mean arterial pressure at 3 months interval	Change in mean arterial pressure (mm of Hg) will be noted	1 year
Secondary	Changes in serum and 24- hour urine sodium	Serum and urine sodium concentration will be measured in meq/L	1 year
Secondary	Incidence of spontaneous bacterial peritonitis (SBP) and other infections	The diagnosis of SBP will be based on neutrophil count in ascitic ?uid 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.	1 year
Secondary	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	1 year
Secondary	Number of patients who develop hyponatremia	Hyponatremia will be defined using serum sodium concentrations of <130meq/L.	1 year
Secondary	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	1 year
Secondary	Number of patients who develop hypokalemia	Hypokalemia will be defined using serum potassium levels <3 meq/L	1 year
Secondary	Number of patients who develop hyperkalemia	hyperkalemia will be defined using serum potassium levels >6 meq/L	1 year