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

• Status: Not yet recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Liver and Biliary Sciences, India
• Treatments: Midodrine; Tolvaptan

Criteria

Inclusion Criteria:

1. Child B/C cirrhosis

2. Hyponatremia( severe)

3. Written informed consent

4. Age-18-70 years

Exclusion Criteria:

1. AKI(1.5mg/dl)

2. Sepsis

3. Underlyig CKD

4. High risk varices

5. Recent Bleed in 2 weeks

6. Acute Symptomatic hyponatremia

7. SIADH

8. Hypothyroidism

9. Severe cardiopulmonary disease

10. Cerebrovascular accident

11. Multiple strokes;

12. Pseudohyponatremia