Clinical trial NCT04816240: Evaluation of Albumin and Midodrine Versus Albumin Alone in Outcome of Refractory Ascites in Patients With Decompensated Cirrhosis.
Official title: Evaluation of Albumin and Midodrine Versus Albumin Alone in Outcome of Refractory Ascites in Patients With Decompensated Cirrhosis - A Double Blind Randomized Controlled Trial."
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Cirrhosis
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2021-03-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The project is about evaluation of albumin and midodrine versus albumin alone in outcome of refractory ascites in patients with decompensated cirrhosis.

Cirrhosis is a leading cause of disability and mortality worldwide. Cirrhosis occurs in 50% of patients over 10 years. Decompensated cirrhosis carries a poor prognosis because the median survival time is about 2 years and it imposes a heavy burden on health care costs mainly due to the need for repeated hospital admission. The mortality is approximately 40% at 1 year and 50% at 2 years (12.7 per 100,000 population). A lot of times the prognosis is poor and the main factors leading to it are - AKI/HRS-NAKI, Hyponatremia, Grade of ascites-Refractory ascites, Sarcopenia, low Mean arterial pressure.

Post review of the literature, it is realized that there are some gap areas -

* It is unknown whether combination of vasoconstrictor with albumin further decreases the need for paracentesis in patients of refractory ascites.
* There are no studies till date on using combination of vasoconstrictor with albumin for refractory ascites.
* There are no studies evaluating the prevalence and incidence of HRS-NAKI using the new definitions in patients with refractory ascites and impact of combining vasoconstrictor and albumin in improving renal outcomes in these patients.

Detailed description: Study population All patients with decompensated cirrhosis with refractory ascites who get admitted under the Department of Hepatology at Institute of Liver and Biliary Sciences, who fulfilthe inclusion criteria, exclusion criteria and provide informed consent

* Study design Single Centre Placebo Controlled an open level Randomised Controlled Trial
* Study period 1 year from ethics approval.
* Sample size Assuming that survival rate with albumin and midodrine is 80%, whereas with albumin alone is 60% ( ie. 20% absolute difference is observed with alpha of 5% power so we need to enroll 170 cases allotted in 2 groups further taking 10% as dropout rate. It was decided to enroll 200 cases allotted in 2 groups randomly by block randomization method taking block size as 10
* Intervention Group A will be treated with SMT + Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (\>75 mm and \<90) and Group B with SMT + Albumin: 80grams/week for 2 weeks followed by 40gram/week + Placebo

Stopping ruleAdverse reaction to Albumin

* Cardiopulmonary compromise
* Allergic reaction

Eligibility criteria: Inclusion Criteria:

- Cirrhosis with refractory ascites

Exclusion Criteria:

- Recent Gastrointestinal bleeding within 7 days

* Systemic arterial hypertension (\>160/90mmhg)
* Presence of hepatocellular carcinoma or portal vein thrombosis, Budd-chiari syndrome.
* Pregnancy
* No use of drugs affecting systemic hemodynamics 7 days prior to enrolment
* Patients with Cardiovascular disease (NYHA \> II) or chronic obstructive pulmonary disease
* Refusal to participate
* Known or suspected hypersensitivity to albumin
* Prior TIPS
* Post liver or kidney transplantation
* Patients enrolled in other clinical trials
* Extrahepatic malignancy
* Patients on cardiac glycosides like digoxin, phenylephrine, ephedrine, thyroid hormones, ergot derivatives, salt retaining steroids like fludrocortisone, MAO inhibitors, alpha blockers metformin and ranitidine (known to have interactions with midodrine)
* Patients with intrinsic kidney disease, organ nephropathy and CKD stage 4 and
* MELD \> 30 and extremely moribend patient

Primary outcomes:
measure: Survival free of transplant and TIPS
timeFrame: 6 months
Secondary outcomes:
measure: Cumulative incidence of liver-related complications
timeFrame: 3 months
measure: Cumulative incidence of liver-related complications
timeFrame: 6 months
measure: Cumulative incidence of liver-related complications
timeFrame: 12 months
measure: Survival free of liver transplant in both groups
timeFrame: 1 year
measure: Survival free of TIPS in both groups
timeFrame: 1 year
measure: Incidence of HRS-AKD, in both groups at 1 year
timeFrame: 1 year
measure: Incidence of HRS-CKD in both groups at 1 year
timeFrame: 1 year
measure: Incidence of HRS AKI in both groups at 1 year
timeFrame: 1 year
measure: Cumulative frequency of large volume paracentesis
timeFrame: 3 months
measure: Cumulative frequency of large volume paracentesis
timeFrame: 6 months
measure: Cumulative frequency of large volume paracentesis
timeFrame: 12 months
measure: Improvement in fraility
timeFrame: 3 months
measure: Improvement in fraility
timeFrame: 6 months
measure: Improvement in fraility
timeFrame: 12 months
measure: Survival free of TIPS
timeFrame: 6 months
measure: Survival free of transplant at 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences
state: Delhi
Study officials:
References: