AscitesPhase 3NCT01349348
Phase III Study of Tolvaptan Tablet to Treat Cirrhosis Ascites
A Phase 3 study testing Tolvaptan in people with Ascites and Hepatic Cirrhosis, run by Otsuka Beijing Research Institute at 1 site in China.
Trial summary
To evaluate the efficacy and safety of Tolvaptan 7.5mg and 15mg in treatment of patients with cirrhosis ascites who fail to response adequately to treatment with common diuretics. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ascites, Hepatic Cirrhosis
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 535 participants
- Where
- 1 siteChina
- Study dates
- Oct 2010to Jul 2012
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with liver cirrhosis clinically or pathologically;
- Patients with ascites confirmed by Type-B ultrasound scan after receiving combination therapies of oral loop diuretics and aldosterone antagonists for at least 4 days with the fixed usage and dosage
- Inpatients or patients who can be hospitalized for this study from Day -3 (Screening) to Day 8 (the day for efficacy evaluation);
- Patients with body weight change within ±1.0 kg in the 2 days prior to initiation of treatment (Day -2 and Day -1)
- Age: 18 to 75 years, inclusive(at the time informed consent is obtained);
- Genders: men or women;
- Patients who have signed informed consent form.
Who cannot join
- Patients with any of the following diseases, complications or symptoms:
- Hepatic encephalopathy (hepatic coma of grade II or higher1）);
- Malignant ascites (patients have tumor cells detected in ascites if malignant ascites be highly suspected);
- Uncontrolled spontaneous bacterial peritonitis;
- Patients who are likely to experience alimentary tract hemorrhage during the study;
- Heart failure (NYHA2） grade III or IV);
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- Anuresis (daily urine volume is less than 100mL);
- Dysuria due to urinary tract stricture, urinary calculus, tumor in the urinary tract or other cause.
- Patients with history of :
- Alimentary tract hemorrhage within 10 days prior to screening;
- Cerebral accident suffered within 30 days prior to screening;
- Past history of hypersensitivity or idiosyncratic reaction to benzazepine derivatives (Benazepril).
- Patients with systolic pressure below 90mmHg at screening;
- Patients with any of the following abnormal laboratory parameters at screening:
- Serum creatinine >1.5x upper limit of normal range;
- Serum Na+>145mmol/L (or higher than upper limit of normal range);
- Serum K+>5.5mmol/L;
- Patients with Child-pugh score3）>12;
- Patients who are unable to take medicine orally;
- Female patients who are pregnant, lactating, or who are at child-bearing age without using acceptable contraceptive means;
- Patients who received blood products including albumin within 4 days prior to the initiation of treatment
- Patients who participated in any clinical trial other than tolvaptan within one month prior to screening;
- Patients who participated in Tolvaptan trials and took Tolvaptan previously;
- Patients otherwise judged by the investigator, to be inappropriate for inclusion in the study.
Trial locations and contacts
1 site in 1 country.
China1 site
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, 200001
About this study
Official title: A Randomized, Double-blinded, Multicenter, Placebo Controlled, Parallel Designed Study, to Evaluate the Efficacy and Safety of Tolvaptan Tablet in Treatment of Patients With Cirrhosis Ascites, Using Diuretics as Initial Treatment
To evaluate the efficacy and safety of Tolvaptan 7.5mg and 15mg in treatment of patients with cirrhosis ascites who fail to response adequately to treatment with common diuretics.
Read the detailed description
For symptoms of fluid retention due to liver diseases (ascites and/or lower extremity edema, i.e. hepatic edema), treatment generally starts with bed rest and a low-salt diet. Aldosterone antagonists and loop diuretics are commonly used diuretics in the treatment of fluid retention due to liver diseases. In aldosterone antagonists' therapy, nevertheless, hyperkalemia is frequently reported, slow onset of action and dose escalation needed also impair its effect. If aldosterone antagonists' therapy is ineffective, loop diuretics as strong diuretics are usually added up. However, Dose escalation of loop diuretics also boost the occurrence of hyponatremia and hypokalemia, and combination of the two drugs provided fastest onset of effectiveness with less adverse events. While, because both diuretics can cause sodium lose which is difficult to prevent and treat, hyponatremia is easy to occur. The combination of aldosterone antagonists and K-sparing diuretics reduces the occurrence of hypokalemia but have little effect on the prevention and treatment of hyponatremia. In addition, there are still some patients who are resistent to loop diuretics or intolerant of an effective diuretic dosage due to adverse events.
Tolvaptan increases the excretion of electrolyte-free water (aquaretic) without changing electrolytes excretion by inhibiting the water reabsorption of collecting duct in kidney. It is demonstrated that Tolvaptan increased urine volume without impairing renal function.
- Conditions
- Ascites, Hepatic Cirrhosis
- Being tested
- Tolvaptan, placebo
- Keywords
- Tolvaptan treatment to ascites and hepatic cirrhosis
- Medical subject headings
- Ascites, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called SAMSCA
tablet, 15 mg, Qd, for 7 days
TolvaptanDrug
Also called SAMSCA
tablet, 7.5 mg, Qd, for 7 days
placeboDrug
Also called Blank tablet
tablet, 7.5/15mg , Qd, 7days.
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan 15mg | Experimental | Tablet;15mg/tab Receives: Drug: Tolvaptan |
| Tolvaptan 7.5mg | Experimental | Tablet;7.5mg/tab Receives: Drug: Tolvaptan |
| Placebo | Placebo comparator | Tolvaptan 0mg/tab Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in body weight after 7 days randomized treatment (Day 8).
Measured: 7 days
Secondary outcomes (2)
Change from baseline in body weight after 4 days randomized treatment (Day 5);
Measured: 4days
The rate of change from baseline in body weight after 4, 7 days randomized treatment (Day 5, Day 8);
Measured: 4 and 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2011 (estimated)
- Study startOct 2010
- Primary completionMay 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AscitesStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 535 participants (actual)
Sponsor and investigators
- Lead sponsor
- Otsuka Beijing Research Institute
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Minde Zeng, Principal investigator, RenJi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01349348
- Sponsor's protocol ID
- 156-08-805-01
- Status last verified
- Oct 2012
- First submitted
- 4 May 2011
- Last updated
- 12 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Tang J, Wang Y, Han T, Mao Q, Cheng J, Ding H, Shang J, Zhang Q, Niu J, Ji F, Chen C, Jia J, Jiang X, Lv N, Gao Y, Wang Z, Wei Z, Chen Y, Zeng M, Mao Y. Tolvaptan therapy of Chinese cirrhotic patients with ascites after insufficient diuretic routine medication responses: a phase III clinical trial. BMC Gastroenterol. 2020 Nov 19;20(1):391. doi: 10.1186/s12876-020-01536-0.
PubMed 33213378Wang 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.
PubMed 30180806
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blinded, Multicenter, Placebo Controlled, Parallel Designed Study, to Evaluate the Efficacy and Safety of Tolvaptan Tablet in Treatment of Patients With Cirrhosis Ascites, Using Diuretics as Initial Treatment
- ClinicalTrials.gov ID
- NCT01349348
- Acronym / sponsor ID
- 156-08-805-01
- Conditions
- Ascites, Hepatic Cirrhosis
- Keywords
- Tolvaptan treatment to ascites and hepatic cirrhosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 535 participants (actual)
- Lead sponsor
- Otsuka Beijing Research InstituteIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- May 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 6 May 2011 (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.
To evaluate the efficacy and safety of Tolvaptan 7.5mg and 15mg in treatment of patients with cirrhosis ascites who fail to response adequately to treatment with common diuretics.
Detailed description
For symptoms of fluid retention due to liver diseases (ascites and/or lower extremity edema, i.e. hepatic edema), treatment generally starts with bed rest and a low-salt diet. Aldosterone antagonists and loop diuretics are commonly used diuretics in the treatment of fluid retention due to liver diseases. In aldosterone antagonists' therapy, nevertheless, hyperkalemia is frequently reported, slow onset of action and dose escalation needed also impair its effect. If aldosterone antagonists' therapy is ineffective, loop diuretics as strong diuretics are usually added up. However, Dose escalation of loop diuretics also boost the occurrence of hyponatremia and hypokalemia, and combination of the two drugs provided fastest onset of effectiveness with less adverse events. While, because both diuretics can cause sodium lose which is difficult to prevent and treat, hyponatremia is easy to occur. The combination of aldosterone antagonists and K-sparing diuretics reduces the occurrence of hypokalemia but have little effect on the prevention and treatment of hyponatremia. In addition, there are still some patients who are resistent to loop diuretics or intolerant of an effective diuretic dosage due to adverse events.
Tolvaptan increases the excretion of electrolyte-free water (aquaretic) without changing electrolytes excretion by inhibiting the water reabsorption of collecting duct in kidney. It is demonstrated that Tolvaptan increased urine volume without impairing renal function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan 15mg | Experimental | Drug: TolvaptanTablet;15mg/tab |
| Tolvaptan 7.5mg | Experimental | Drug: TolvaptanTablet;7.5mg/tab |
| Placebo | Placebo comparator | Drug: placeboTolvaptan 0mg/tab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients diagnosed with liver cirrhosis clinically or pathologically;
- Patients with ascites confirmed by Type-B ultrasound scan after receiving combination therapies of oral loop diuretics and aldosterone antagonists for at least 4 days with the fixed usage and dosage
- Inpatients or patients who can be hospitalized for this study from Day -3 (Screening) to Day 8 (the day for efficacy evaluation);
- Patients with body weight change within ±1.0 kg in the 2 days prior to initiation of treatment (Day -2 and Day -1)
- Age: 18 to 75 years, inclusive(at the time informed consent is obtained);
Key exclusion criteria (24 listed)
- Patients with any of the following diseases, complications or symptoms:
- Patients with history of :
- Patients with systolic pressure below 90mmHg at screening;
- Patients with any of the following abnormal laboratory parameters at screening:
- Patients with Child-pugh score3）>12;
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: SAMSCAtablet, 15 mg, Qd, for 7 days | Drug | Tolvaptan 15mg |
| TolvaptanAlso: SAMSCAtablet, 7.5 mg, Qd, for 7 days | Drug | Tolvaptan 7.5mg |
| placeboAlso: Blank tablettablet, 7.5/15mg , Qd, 7days. | Drug | Placebo |
Primary outcome
Change from baseline in body weight after 7 days randomized treatment (Day 8).
Time frame: 7 days
2 secondary outcomes
Change from baseline in body weight after 4 days randomized treatment (Day 5);
Time frame: 4days
The rate of change from baseline in body weight after 4, 7 days randomized treatment (Day 5, Day 8);
Time frame: 4 and 7 days
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 12 Oct 2012.
- Derived from this study: PubMed 33213378Tang J, Wang Y, Han T, Mao Q, Cheng J, Ding H, Shang J, Zhang Q, Niu J, Ji F, Chen C, Jia J, Jiang X, Lv N, Gao Y, Wang Z, Wei Z, Chen Y, Zeng M, Mao Y. Tolvaptan therapy of Chinese cirrhotic patients with ascites after insufficient diuretic routine medication responses: a phase III clinical trial. BMC Gastroenterol. 2020 Nov 19;20(1):391. doi: 10.1186/s12876-020-01536-0.
- Derived from this study: PubMed 30180806Wang 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.
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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.
Minde Zeng principal investigator
RenJi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tolvaptan in people with Ascites and Hepatic Cirrhosis, run by Otsuka Beijing Research Institute at 1 site 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 7 inclusion and 24 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 12 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change from baseline in body weight after 7 days randomized treatment (Day 8). (time frame: 7 days). 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 NCT01349348, which also lists 2 linked publications.
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 12 Oct 2012.