Liver CirrhosisOASISNCT01850940
Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia
An observational study of Liver Cirrhosis and Hyponatremia, run by Beijing Friendship Hospital at 19 sites in China.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis, Hyponatremia
- What is being tested?
- Tolvaptan and conventional thearpy
- How many people
- 98 participants
- Where
- 19 sitesChina
- Study dates
- Jan 2013to May 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population of this study will be patients with established cirrhosis and hyponatremia.
Who may be able to join
- Age no less than 18 years;
- Confirmed cirrhosis by histology or radiological features of cirrhosis and clinical features of portal hypertension;
- Serum sodium level less than 135 mmol/L;
- Inpatients.
Who cannot join
- Clinical features of hypovolemia;
- Systolic blood pressure less than 90 mmHg;
- Life expectancy less than one month;
- History of variceal bleeding in the last six months;
- Hepatic encephalopathy or peritonitis in the last two weeks;
- Serum creatinine more than 3.5 mg/dl;
- Severe cardiopulmonary disease;
- Urinary tract obstruction.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
China19 sites
Beijing Ditan Hospital
Beijing, Beijing Municipality, 100018
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Peking University People's Hospital
Beijing, Beijing Municipality, 100044
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 100050
Beijing Youan Hospital
Beijing, Beijing Municipality, 100069
Shanghai Renji Hospital
Beijing, Beijing Municipality, 200127
302 Military Hospital Integrative Medicine
Beijing, Beijing Municipality
302 Military Hospital Liver Failure Center
Beijing, Beijing Municipality
The Third Affiliated Hospital of Sun Yat-sen University
Guangdong, Guangdong, 510630
Guangdong General Hospital
Guangdong, Guangdong
Zhujiang Hospital of Southern Medical University
Guangdong, Guangdong
Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine
Shanghai, Shanghai Municipality, 200021
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200032
Shanghai Huashan Hospital
Shanghai, Shanghai Municipality, 200040
85 Militay Hospital
Shanghai, Shanghai Municipality, 200052
Shanghai Xinhua Hospital
Shanghai, Shanghai Municipality, 200092
Shanghai Putuo District Central Hospital
Shanghai, Shanghai Municipality, 200333
Shanghai Changhai Hospital
Shanghai, Shanghai Municipality, 200433
Shanghai Public Health Clinical Center
Shanghai, Shanghai Municipality, 201052
About this study
Official title: Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia - A Multi-center Prospective Cohort Study
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.
Read the 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
- Being tested
- Tolvaptan, conventional thearpy
- Keywords
- Cirrhotic Patients, Hyponatremia, tolvaptan
- Medical subject headings
- Liver Cirrhosis, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called OPC-41061
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 thearpyOther
Also called basic therapy
conventional therapy with salt limitation ,et al
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan Group | Tolvaptan,qd, po Receives: Drug: Tolvaptan | |
| Conventional therapy | control group:Conventional therapy without tolvaptan Receives: Other: conventional thearpy |
What is being measured
The primary outcome is the main question the study is designed to answer.
the proportion of subjects with normal serum sodium level (135-145 mmol/l)
evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia
Measured: day 7
Secondary outcomes (6)
change in sodium level from baseline
evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia
Measured: day 7 and day 30
quality of life (EQ-5D-3L)
evaluate the efficacy of tolvaptan in cirrhotic patients
Measured: day 7 and day 30
change in body weight
evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia
Measured: day 7 and day 30
edema
evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia
Measured: day 7 and day 30
renal function
evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients
Measured: day 7 and day 30
mortality and liver-related complications
evaluate the short- to intermediate-term safety of tolvaptan in cirrhotic patients
Measured: day 7 and day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study startJan 2013
- Primary completionSep 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Beijing Friendship HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Friendship Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Chinese University of Hong Kong
- Responsible party
- Principal investigator, Jia Ji-Dong, Beijing Friendship Hospital
- Investigators
- Dong J Jia, doctor, Study director, Beijing Friendship Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01850940
- Sponsor's protocol ID
- OASIS
- Acronym
- OASIS
- Status last verified
- Jul 2015
- First submitted
- 1 Apr 2013
- Last updated
- 28 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Tolvaptan in Cirrhotic Patients With Hyponatremia - A Multi-center Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT01850940
- Acronym / sponsor ID
- OASIS / OASIS
- Conditions
- Liver Cirrhosis, Hyponatremia
- Keywords
- Cirrhotic Patients, Hyponatremia, tolvaptan
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Beijing Friendship HospitalUniversity, hospital or other
- Collaborators
- Chinese University of Hong Kong
- Study start
- Jan 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 10 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan Group | – | Drug: TolvaptanTolvaptan,qd, po |
| Conventional therapy | – | Other: conventional thearpycontrol group:Conventional therapy without tolvaptan |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population of this study will be patients with established cirrhosis and hyponatremia.
Key inclusion criteria (4 listed)
- Age no less than 18 years;
- Confirmed cirrhosis by histology or radiological features of cirrhosis and clinical features of portal hypertension;
- Serum sodium level less than 135 mmol/L;
- Inpatients.
Key exclusion criteria (8 listed)
- Clinical features of hypovolemia;
- Systolic blood pressure less than 90 mmHg;
- Life expectancy less than one month;
- History of variceal bleeding in the last six months;
- Hepatic encephalopathy or peritonitis in the last two weeks;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolvaptanAlso: OPC-41061Tolvaptan (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. | Drug | Tolvaptan Group |
| conventional thearpyAlso: basic therapyconventional therapy with salt limitation ,et al | Other | Conventional therapy |
Primary outcome
the proportion of subjects with normal serum sodium level (135-145 mmol/l)
Time frame: day 7
evaluate the efficacy of tolvaptan in cirrhotic patients with hyponatremia
6 secondary outcomes
change in sodium level from baseline
Time frame: day 7 and day 30
quality of life (EQ-5D-3L)
Time frame: day 7 and day 30
change in body weight
Time frame: day 7 and day 30
edema
Time frame: day 7 and day 30
renal function
Time frame: day 7 and day 30
mortality and liver-related complications
Time frame: day 7 and day 30
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2015.
- Results publicationKim 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dong J Jia, doctor study director
Beijing Friendship Hospital
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Cirrhosis and Hyponatremia, run by Beijing Friendship Hospital at 19 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the proportion of subjects with normal serum sodium level (135-145 mmol/l) (time frame: day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01850940, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2015.