Clinical trial NCT00664014: A Phase 2 Efficacy and Safety Study of the Tolvaptan Tablets in Patients With Non-hypovolemic Non-acute Hyponatremia
Official title: Randomized, Double-blind, Multicenter, Placebo-controlled (Standard Therapy + Placebo), Phase 2 Efficacy and Safety Study of the Tolvaptan Tablets in Patients With Non-hypovolemic Non-acute Hyponatremia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypovolemic Hyponatremia
Keywords: hyponatremia
Non-acute and non hypovolemic hyponatremia
Lead sponsor: Otsuka Beijing Research Institute
Sponsor class: INDUSTRY
Collaborators: name: Otsuka Pharmaceutical Co., Ltd.
First posted: 2008-04-22
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, multicenter, placebo-controlled (standard therapy + placebo), phase 2 efficacy and safety study of the Tolvaptan tablets in treatment of patients with non-hypovolemic non-acute hyponatremia arising from a variety of etiologies. 240 (120 in each group) patients are to be enrolled randomly into Tolvaptan group or placebo group. Subjects in Tolvaptan group will receive standard therapy + Tolvaptan (15-60mg/day), while those in control group receiving standard therapy + placebo. The starting dose of tolvaptan is 15mg and it could be titrated up to 30mg and then,if necessary, to the maximum of 60mg according to a certain titration scheme based on patients' response of serum sodium level. The study includes a 2-day screening period from day -2 to day -1, 7-day inpatient study treatment (day 1 to day 7 ). After study treatment, subjects will be Followed-up on safety events on day 14 - 16. The Primary Efficacy Variable is the change of serum sodium from baseline. For patients with Congestive Heart Failure (CHF) or hepatic cirrhosis, change of body weight, fluid balance and symptoms improvement of CHF and hepatic edema will be assessed as secondary efficacy variables.


Eligibility criteria: Inclusion Criteria:

1. Informed consent.
2. Age:18～75 (when informed consent is obtained)，male or female.
3. Non-hypovolemic and non acute hyponatremia with a Serum sodium \< 135mEq/L before randomization. (main underlying diseases include CHF, hepatic cirrhosis with edema, SIADH and others)
4. In-patient subjects.

Primary outcomes:
measure: The change of average daily Area Under the Curve (AUC) of serum sodium by day 4 and 7 comparing with baseline serum sodium level within the double-blind therapy period.
timeFrame: 4 and 7 days
Secondary outcomes:
measure: For CHF and hepatic edema patients, improvement of symptoms and relevant physical examination measures or ultrasound test findings . Other secondary efficacy variables on blood serum sodium, fluid balance or body weight change.
timeFrame: 4 or 7 days
Other outcomes:
Locations:
city: Changsha
country: China
facility: Department of Cardiology, the Third Xiangya Hospital, Central South University
state: Hunan
city: Changsha
country: China
facility: Department of Cardiology, Xiangya Hospital, Central South University
state: Hunan
city: Changchun
country: China
facility: Cardiology, Jilin University Second Hospital
state: Jilin
city: Chengdu
country: China
facility: Endocrinology, West China Hospital Sichuan University
state: Sichuan
city: Beijing
country: China
facility: Cardiology / Endocrinology, Peking Union Medical College Hospital
city: Beijing
country: China
facility: Cardiology / Hepatology, Beijing Friendship Hospital
city: Beijing
country: China
facility: Cardiology/Endocrinology/Infection, Beijing University First Hospital
city: Beijing
country: China
facility: Endocrinology, No. 301 hospital
city: Beijing
country: China
facility: Hepatology, Beijing Renmin Hospital
city: Chongqing
country: China
facility: Hepatology/Endocrinology, Chongqing Medical University Second Hospital
city: Shanghai
country: China
facility: Hepatology / Endocrinology, Shanghai Changzheng Hospital
city: Tianjin
country: China
facility: Cardiology, Tianjin Medical University Second Hospital
city: Tianjin
country: China
facility: Endocrinology, Tianjin General Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Wenling Zhu
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking Union Medical College Hospital
name: Feng Gu
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Friendship Hospital
name: Jidong Jia
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang S, Zhang X, Han T, Xie W, Li Y, Ma H, Liebe R, Weng H, Ding HG. Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia. BMC Gastroenterol. 2018 Sep 4;18(1):137. doi: 10.1186/s12876-018-0857-0.
citation: Chen S, Zhao JJ, Tong NW, Guo XH, Qiu MC, Yang GY, Liu ZM, Ma JH, Zhang ZW, Gu F. Randomized, double blinded, placebo-controlled trial to evaluate the efficacy and safety of tolvaptan in Chinese patients with hyponatremia caused by SIADH. J Clin Pharmacol. 2014 Dec;54(12):1362-7. doi: 10.1002/jcph.342.