Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia

Study Overview
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Brief Summary
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This is a phase IV, open-label, prospective cohort study for 7 days.The recommended starting dose of tolvaptan is 15 mg daily orally. The dose may be titrated on the next day at 15 mg intervals up to 60 mg daily according to the serum sodium level response.Serum sodium level, change in sodium level from baseline, quality of life (EQ-5D-3L), change in body weight, edema, renal function, mortality and liver-related complications on day 7 and day 30 to evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia.

Detailed Description
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Tolvaptan is an effective treatment for hyponatremia. However, cirrhotic patients were underrepresented in previous studies. The pattern of use and efficacy of tolvaptan in real-life clinical practice are currently unknown.The objective of this study is to evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia. The secondary objective is to evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients.This will be a phase IV, open-label, prospective cohort study for 7 days. Although not mandatory, study subjects are encouraged to undergo follow-up assessments at 1 month.Subjects will be evaluated at designated time points after initiation of therapy. The primary efficacy endpoint is the proportion of subjects with normal serum sodium level (135-145 mmol/l) on day 7. The secondary efficacy endpoints are serum sodium level, change in sodium level from baseline, quality of life (EQ-5D-3L), change in body weight, edema, renal function, mortality and liver-related complications on day 7 and day 30.

Official Title
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Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia - A Multi-center Prospective Cohort Study

Conditions
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Liver Cirrhosis, Hyponatremia

Intervention / Treatment
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* Drug: Tolvaptan
* Other: conventional thearpy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age no less than 18 years; Confirmed cirrhosis by histology or radiological features of cirrhosis and clinical features of portal hypertension; Serum sodium level less than 135 mmol/L; Inpatients. Exclusion criteria: Clinical features of hypovolemia; Systolic blood pressure less than 90 mmHg; Life expectancy less than one month; History of variceal bleeding in the last six months; Hepatic encephalopathy or peritonitis in the last two weeks; Serum creatinine more than 3.5 mg/dl; Severe cardiopulmonary disease; Urinary tract obstruction.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tolvaptan Group<br>Tolvaptan,qd, po | Drug: Tolvaptan<br>* Tolvaptan (OPC-41061) is a benzazepine derivative synthesized by Otsuka Pharmaceutical Company, Ltd. Tolvaptan was approved for the treatment of specific forms of hyponatremia by the United States (US) Food and Drug Administration (FDA) in May 2009, the European Medicines Agency on Aug 2009, Japan (Oct 2010), China (Sep 2011) and Korea (Sep 2011). Tolvaptan was approved for the adjunct treatment of volume overload in heart failure by the Japanese Ministry of Health, Labour, and Welfare (MHLW) in Oct 2010. It is also being developed for the treatment of autosomal dominant polycystic kidney disease (ADPKD), and for the treatment of hepatic edema.<br>* Other names: OPC-41061;|
| Conventional therapy<br>control group:Conventional therapy without tolvaptan | Other: conventional thearpy<br>* conventional therapy with salt limitation ,et al<br>* Other names: basic therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of subjects with normal serum sodium level (135-145 mmol/l) | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia | day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in sodium level from baseline | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia | day 7 and day 30 | 
| quality of life (EQ-5D-3L) | evaluate the efficacy of tolvaptan in cirrhotic patients | day 7 and day 30 | 
| change in body weight | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia | day 7 and day 30 | 
| edema | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia | day 7 and day 30 | 
| renal function | evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients | day 7 and day 30 | 
| mortality and liver-related complications | evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients | day 7 and day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhotic Patients, Hyponatremia, tolvaptan