Hyponatremia, Liver Cirrhosis
Conditions
Keywords
Cirrhotic Patients, Hyponatremia, tolvaptan
Brief summary
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
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.
Interventions
DRUGTolvaptan
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.
OTHERconventional thearpy
conventional therapy with salt limitation ,et al
Sponsors
Chinese University of Hong Kong
Beijing Friendship Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age no less than 18 years; 2. Confirmed cirrhosis by histology or radiological features of cirrhosis and clinical features of portal hypertension; 3. Serum sodium level less than 135 mmol/L; 4. Inpatients.
Exclusion criteria
1. Clinical features of hypovolemia; 2. Systolic blood pressure less than 90 mmHg; 3. Life expectancy less than one month; 4. History of variceal bleeding in the last six months; 5. Hepatic encephalopathy or peritonitis in the last two weeks; 6. Serum creatinine more than 3.5 mg/dl; 7. Severe cardiopulmonary disease; 8. Urinary tract obstruction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the proportion of subjects with normal serum sodium level (135-145 mmol/l) | day 7 | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| quality of life (EQ-5D-3L) | day 7 and day 30 | evaluate the efficacy of tolvaptan in cirrhotic patients |
| change in body weight | day 7 and day 30 | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia |
| change in sodium level from baseline | day 7 and day 30 | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia |
| renal function | day 7 and day 30 | evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients |
| mortality and liver-related complications | day 7 and day 30 | evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients |
| edema | day 7 and day 30 | evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia |
Countries
China
Outcome results
None listed