Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia

NCT ID: NCT01850940

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 98 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-05-31

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.

Conditions

Liver Cirrhosis; Hyponatremia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Tolvaptan Group

Tolvaptan,qd, po

Tolvaptan

Intervention Type: DRUG

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.

Conventional therapy

control group:Conventional therapy without tolvaptan

conventional thearpy

Intervention Type: OTHER

conventional therapy with salt limitation ,et al

Interventions

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.

Intervention Type: DRUG

conventional thearpy

conventional therapy with salt limitation ,et al

Intervention Type: OTHER

Other Intervention Names

OPC-41061; basic therapy

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: collaborator

Beijing Friendship Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jia Ji-Dong

Direcror of the Liver Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dong J Jia, doctor

Role: STUDY_DIRECTOR

Beijing Friendship Hospital

Locations

Beijing Ditan Hospital

Beijing, Beijing Municipality, China

Peking University First Hospital

Beijing, Beijing Municipality, China

Peking University People's Hospital

Beijing, Beijing Municipality, China

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Beijing Youan Hospital

Beijing, Beijing Municipality, China

Shanghai Renji Hospital

Beijing, Beijing Municipality, China

302 Military Hospital Integrative Medicine

Beijing, Beijing Municipality, China

302 Military Hospital Liver Failure Center

Beijing, Beijing Municipality, China

The Third Affiliated Hospital of Sun Yat-sen University

Guangdong, Guangdong, China

Guangdong General Hospital

Guangdong, Guangdong, China

Zhujiang Hospital of Southern Medical University

Guangdong, Guangdong, China

Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine

Shanghai, Shanghai Municipality, China

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Shanghai Huashan Hospital

Shanghai, Shanghai Municipality, China

85 Militay Hospital

Shanghai, Shanghai Municipality, China

Shanghai Xinhua Hospital

Shanghai, Shanghai Municipality, China

Shanghai Putuo District Central Hospital

Shanghai, Shanghai Municipality, China

Shanghai Changhai Hospital

Shanghai, Shanghai Municipality, China

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, China

Countries

China

References

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 mortality in Chinese patients with chronic hepatitis B. Liver Transpl 2007;13:1228-35. Serste T, Gustot T, Rautou PE, et al. Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites. J Hepatol 2012;57:274-80. Sanyal AJ, Bosch J, Blei A, et al. Portal hypertension and its complications. Gastroenterology 2008;134:1715-28. Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006;355:2099-112. Gheorghiade M, Gattis WA, O'Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 2004;291:1963-71. Cardenas A, Gines P, Marotta P, et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J Hepatol 2012;56:571-8.

Reference Type: RESULT

Other Identifiers

OASIS

Identifier Type: -

Identifier Source: org_study_id