Clinical trial NCT01850940: Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia
Official title: Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia - A Multi-center Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Cirrhosis
Hyponatremia
Keywords: Cirrhotic Patients
Hyponatremia
tolvaptan
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Chinese University of Hong Kong
First posted: 2013-05-10
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population of this study will be patients with established cirrhosis and hyponatremia.

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.

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.

Primary outcomes:
measure: the proportion of subjects with normal serum sodium level (135-145 mmol/l)
timeFrame: day 7
Secondary outcomes:
measure: change in sodium level from baseline
timeFrame: day 7 and day 30
measure: quality of life (EQ-5D-3L)
timeFrame: day 7 and day 30
measure: change in body weight
timeFrame: day 7 and day 30
measure: edema
timeFrame: day 7 and day 30
measure: renal function
timeFrame: day 7 and day 30
measure: mortality and liver-related complications
timeFrame: day 7 and day 30
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital
state: Beijing
city: Beijing
country: China
facility: Shanghai Renji Hospital
state: Beijing
city: Beijing
country: China
facility: 302 Military Hospital Integrative Medicine
state: Beijing
city: Beijing
country: China
facility: 302 Military Hospital Liver Failure Center
state: Beijing
city: Guangdong
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangdong
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangdong
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Shanghai
country: China
facility: Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Huashan Hospital
state: Shanghai
city: Shanghai
country: China
facility: 85 Militay Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Xinhua Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Putuo District Central Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
Study officials:
affiliation: Beijing Friendship Hospital
name: Dong J Jia, doctor
role: STUDY_DIRECTOR
References:
citation: 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.