Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia (OASIS)

This study has been completed.
Sponsor:
Collaborator:
Chinese University of Hong Kong
Information provided by (Responsible Party):
Jia Ji-Dong, Beijing Friendship Hospital
ClinicalTrials.gov Identifier:
NCT01850940
First received: April 1, 2013
Last updated: July 27, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Liver Cirrhosis
Hyponatremia
Drug: Tolvaptan
Other: conventional thearpy
Phase 3

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia - A Multi-center Prospective Cohort Study

Resource links provided by NLM:


Further study details as provided by Beijing Friendship Hospital:

Primary Outcome Measures:
  • the proportion of subjects with normal serum sodium level (135-145 mmol/l) [ Time Frame: day 7 ] [ Designated as safety issue: No ]
    evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia


Secondary Outcome Measures:
  • change in sodium level from baseline [ Time Frame: day 7 and day 30 ] [ Designated as safety issue: No ]
    evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia

  • quality of life (EQ-5D-3L) [ Time Frame: day 7 and day 30 ] [ Designated as safety issue: No ]
    evaluate the efficacy of tolvaptan in cirrhotic patients

  • change in body weight [ Time Frame: day 7 and day 30 ] [ Designated as safety issue: No ]
    evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia

  • edema [ Time Frame: day 7 and day 30 ] [ Designated as safety issue: No ]
    evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia

  • renal function [ Time Frame: day 7 and day 30 ] [ Designated as safety issue: Yes ]
    evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients

  • mortality and liver-related complications [ Time Frame: day 7 and day 30 ] [ Designated as safety issue: Yes ]
    evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients


Biospecimen Retention:   Samples Without DNA

plasma


Enrollment: 98
Study Start Date: January 2013
Study Completion Date: May 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Tolvaptan Group
Tolvaptan,qd, po
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 Name: OPC-41061
Conventional therapy
control group:Conventional therapy without tolvaptan
Other: conventional thearpy
conventional therapy with salt limitation ,et al
Other Name: basic therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

The study population of this study will be patients with established cirrhosis and hyponatremia.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01850940

Locations
China, Beijing
302 Military Hospital Integrative Medicine
Beijing, Beijing, China
302 Military Hospital Liver Failure Center
Beijing, Beijing, China
Beijing Ditan Hospital
Beijing, Beijing, China, 100018
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing, China, 100050
Beijing Youan Hospital
Beijing, Beijing, China, 100069
Peking University First Hospital
Beijing, Beijing, China, 100034
Peking University People's Hospital
Beijing, Beijing, China, 100044
Shanghai Renji Hospital
Beijing, Beijing, China, 200127
China, Guangdong
Zhujiang Hospital of Southern Medical University
Guangdong, Guangdong, China
The Third Affiliated Hospital of Sun Yat-sen University
Guangdong, Guangdong, China, 510630
Guangdong General Hospital
Guangdong, Guangdong, China
China, Shanghai
85 Militay Hospital
Shanghai, Shanghai, China, 200052
Shanghai Changhai Hospital
Shanghai, Shanghai, China, 200433
Zhongshan Hospital Fudan University
Shanghai, Shanghai, China, 200032
Shanghai Public Health Clinical Center
Shanghai, Shanghai, China, 201052
Shanghai Putuo District Central Hospital
Shanghai, Shanghai, China, 200333
Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine
Shanghai, Shanghai, China, 200021
Shanghai Xinhua Hospital
Shanghai, Shanghai, China, 200092
Shanghai Huashan Hospital
Shanghai, Shanghai, China, 200040
Sponsors and Collaborators
Beijing Friendship Hospital
Chinese University of Hong Kong
Investigators
Study Director: Dong J Jia, doctor Beijing Friendship Hospital
  More Information

Publications:
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.

Responsible Party: Jia Ji-Dong, Direcror of the Liver Research Center, Beijing Friendship Hospital
ClinicalTrials.gov Identifier: NCT01850940     History of Changes
Other Study ID Numbers: OASIS
Study First Received: April 1, 2013
Last Updated: July 27, 2015
Health Authority: China: Food and Drug Administration

Keywords provided by Beijing Friendship Hospital:
Cirrhotic Patients
Hyponatremia
tolvaptan

Additional relevant MeSH terms:
Hyponatremia
Liver Cirrhosis
Digestive System Diseases
Liver Diseases
Metabolic Diseases
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on July 30, 2015