To Study Effect of the Combination of Midodrine and Tolvaptan Versus Tolvaptan Alone in Patients With Severe Hyponatremia in Cirrhosis(TOLMINA Trial)

NCT05060523 | Unknown

• 1 other identifier: ILBS-Cirrhosis-42
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

In this randomized controlled trial , The patients who satisfy the below inclusion and exclusion criteria will be included and they will be randomised, according to 2 groups ( in total 110patients in each group) to receive either Midodrine+Tolvaptan or tolvaptan+placebo for 7 days followed by follow up for 1 month. These patients will be admitted to the hospital from OPD or emergency. In patients with cirrhosis with Patients with cirrhosis -there are two types of hyponatremia. hyponatremia is due to important losses of extracellular fluid, most commonly from the kidneys (because of overdiuresis due to treatment with excessive doses of diuretics) or from the gastrointestinal tract( hypovolemic hyponatremia) hyponatremia develops in the setting of expanded extracellular fluid volume and plasma volume with ascites and edema.This condition is known as hypervolemic or dilutional hyponatremia.A marked impairment of renal solute-free water excretion, resulting in disproportionate renal retention of water with respect to sodium retention.In SALT trail showed that tolvaptan showed improvement in Na+ concentration from baseline at 4 ,30 day. It acts on by increasing free water generation by blocking ADH receptors in distal convoluted tubule. A study by Patel et al in 2017 showed that midodrine also increasing the Na+ by increasing the free water delivery to distal convoluted tubules(in cirrhosis usually there is less water delivery to distal convoluted tubules in view of less GFR).Till now there is no study has been done as combination of midodrine and tolvaptan whether superior to tolvaptan alone or not .So our aim is to study combination of midodrine and tolvaptan verses tolvaptan alone in patients with hyponatremia.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Improvement in Na+ to 125meq/L

  1 week

Secondary Outcomes (18)

• Improvement in Na + (120 -125 meq/L)

  3 days

• Improvement in Na + (120 -125 meq/L)

  5 days

• Changes in Serum osmolality

  0,1day,3day,1week ,2 week,1 month

• Changes in urine volume

  0,1day,3day,1week ,2 week,1 month

• Changes in urinay Na + excretion in body

  0,1day,3day,1week ,2 week,1 month

Study Arms (2)

Tolvaptan with Midodrine

EXPERIMENTAL

Drug: Tolvaptan Tablets; Drug: Midodrine Oral Tablet

Tolvaptan with Placebo

ACTIVE COMPARATOR

Drug: Tolvaptan Tablets; Other: Placebo

Interventions

Tolvaptan Tablets DRUG

• Tolvaptan15 mg once a day for 7 days, stat with 7.5 mg and titrate to 15 mg in 24 hours max30 mg

Tolvaptan with Midodrine; Tolvaptan with Placebo

Midodrine Oral Tablet DRUG

• Midodrine 5 mg at "0" hours and then 5 mg every 8 hours to maintain Target MAP-80

Tolvaptan with Midodrine

Placebo OTHER

Placebo of Midodrine

Tolvaptan with Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Child B/C cirrhosis
• Hyponatremia( severe)
• Written informed consent
• Age-18-70 years

You may not qualify if:

• AKI(1.5mg/dl)
• Sepsis
• Underlyig CKD
• High risk varices
• Recent Bleed in 2 weeks
• Acute Symptomatic hyponatremia
• SIADH
• Hypothyroidism
• Severe cardiopulmonary disease
• Cerebrovascular accident
• Multiple strokes;
• Pseudohyponatremia

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Tolvaptan; Midodrine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Central Study Contacts

Dr G. Srinivasa Reddy, MD

CONTACT

01146300000; srinivasareddygolamari@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: September 29, 2021
• Study Start: September 19, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: November 29, 2021

Record last verified: 2021-08

Locations

IN (1)