Midodrine and Albumin in Patients With Refractory Ascites

NCT04621617 | Unknown Phase 3 DMC

• 1 other identifier: IEC-06/2020-1691
• Study Type: interventional
• Target: 114
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Refractory Ascites

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change in estimated glomerular filtration rate (eGFR) measured by modified diet in renal disease 6 (MDRD6) formula at 3 months intervals

  1 year

• Changes in concentration of albumin at 3 months intervals

  1 year

• Change in model for end stage liver disease (MELD) score

  1 year

• Change in mean arterial pressure at 3 months interval

  1 year

• Changes in serum and 24- hour urine sodium

  1 year

Study Arms (3)

Albumin + Midodrine + SMT

ACTIVE COMPARATOR

Human albumin plus oral midodrine

Drug: Albumin; Drug: Midodrine; Drug: Standard medical therapy (SMT)

Albumin + SMT

ACTIVE COMPARATOR

Human albumin plus placebo of midodrine

Drug: Albumin; Drug: Standard medical therapy (SMT)

SMT

PLACEBO COMPARATOR

standard medical therapy plus placebo of midodrine

Drug: Standard medical therapy (SMT)

Interventions

Albumin DRUG

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

Albumin + Midodrine + SMT; Albumin + SMT

Midodrine DRUG

Oral Midodrine will be given at a dose of 7.5 mg three times in a day

Albumin + Midodrine + SMT

Standard medical therapy (SMT) DRUG

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.

Albumin + Midodrine + SMT; Albumin + SMT; SMT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years
• Refractory ascites in cirrhosis of any etiology

You may not qualify if:

• Mixed ascites: cirrhosis plus another cause of ascites
• Gastrointestinal bleed within 7 days of enrolment.
• Presence of hepatorenal syndrome
• Hepatic encephalopathy grade 2 or higher
• Infection within 1 month preceding the study
• Cardiovascular disease (ejection fraction \< 35% or abnormal ECG) or arterial hypertension (BP \> 140/90 mm of Hg)
• 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
• Presence of hepatocellular carcinoma or portal vein thrombosis
• Patient not willing for study.
• Patient opting for liver transplantation/ transjugular intrahepatic portosystemic shunt

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

MeSH Terms

Conditions

Ascites

Interventions

Albumins; Midodrine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Virendra Singh, MD, DM

  PGIMER, Chandigarh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virendra Singh, MD, DM

CONTACT

0172-275-6338; virendrasingh100@hotmail.com

Amandeep Singh, MD

CONTACT

9815252928; amandeep48@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head, Department of Hepatology

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 9, 2020
• Study Start: November 1, 2020
• Primary Completion: December 1, 2021
• Study Completion: April 1, 2022
• Last Updated: November 9, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share