Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia

Liver Cirrhosis Clinical Trial

— OASIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01850940
• Other study ID #: OASIS
• Status: Completed
• Phase: Phase 3
• First received: April 1, 2013
• Last updated: July 27, 2015
• Start date: January 2013
• Est. completion date: May 2015

Study information

• Verified date: July 2015
• Source: Beijing Friendship Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: May 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hyponatremia
• Liver Cirrhosis

Intervention

Drug:
• Tolvaptan
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.

Other:
• conventional thearpy
conventional therapy with salt limitation ,et al

Locations

Country	Name	City	State
China	302 Military Hospital Integrative Medicine	Beijing	Beijing
China	302 Military Hospital Liver Failure Center	Beijing	Beijing
China	Beijing Ditan Hospital	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Youan Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Shanghai Renji Hospital	Beijing	Beijing
China	Guangdong General Hospital	Guangdong	Guangdong
China	The Third Affiliated Hospital of Sun Yat-sen University	Guangdong	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangdong	Guangdong
China	85 Militay Hospital	Shanghai	Shanghai
China	Shanghai Changhai Hospital	Shanghai	Shanghai
China	Shanghai Huashan Hospital	Shanghai	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai	Shanghai
China	Shanghai Putuo District Central Hospital	Shanghai	Shanghai
China	Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine	Shanghai	Shanghai
China	Shanghai Xinhua Hospital	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Friendship Hospital	Chinese University of Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (1)

Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med 2008;359:1018-26. Wong VW, Chim AM, Wong GL, et al. Performance of the new MELD-Na score in predicting 3-month and 1-year m

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	change in sodium level from baseline	evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia	day 7 and day 30	No
Secondary	quality of life (EQ-5D-3L)	evaluate the efficacy of tolvaptan in cirrhotic patients	day 7 and day 30	No
Secondary	change in body weight	evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia	day 7 and day 30	No
Secondary	edema	evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia	day 7 and day 30	No
Secondary	renal function	evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients	day 7 and day 30	Yes
Secondary	mortality and liver-related complications	evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients	day 7 and day 30	Yes