AscitesPhase 3NSBBNCT02649335
To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites
A Phase 3 study testing Propranolol and Endoscopic variceal ligation (EVL) in people with Ascites, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
Cirrhosis is the leading cause of death in India and worldwide and leading causes in developed world include alcoholic liver disease, hepatitis C, and more recently, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ascites
- What is being tested?
- Propranolol and Endoscopic variceal ligation (EVL)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 1 siteIndia
- Study dates
- 1 Jul 2015to 30 Dec 2016
- 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
- Cirrhosis of any etiology with grade 2 ascites including refractory patients and varices/variceal hemorrhage requiring prophylaxis
- Cirrhosis diagnosed by clinical, analytical, and ultrasonographic findings or available histological findings
- Both inpatient and outpatient
- Child B or C status
Who cannot join
- Active infection or recent infection < 2 weeks
- Hepatic encephalopathy grade 2 or higher
- Renal dysfunction at the time of inclusion
- Presence of hepatocellular carcinoma or portal vein thrombosis
- Active alcoholism
- Pregnancy
Show all 9Show fewer
- HIV infection
- Severe heart, respiratory or contraindications for beta blockers(severe chronic obstructive pulmonary disease, severe asthma, severe insulin-dependent diabetes mellitus, bradyarrhythmia)
- Not giving consent
Trial locations and contacts
1 site in 1 country.
India1 site
Department of Hepatology,Postgraduate Institute of Medical Education and Research
Chandigarh
About this study
Cirrhosis is the leading cause of death in India and worldwide and leading causes in developed world include alcoholic liver disease, hepatitis C, and more recently, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH). As cirrhosis advances, portal hypertension develops, resulting in complications such as ascites, hepatic encephalopathy, and variceal hemorrhage.
Ascites is the most common major complication of cirrhosis, occurring in 50-60% of patients within ten years of diagnosis . Development of ascites is an ominous landmark in disease progression as 15% of patients with ascites will die within 1 year, and 44% within 5 years. Less than 10% patients develop refractory ascites and is associated with a poor prognosis with a high mortality, approximately 50% within 6 months and 75% at 1 year with the median survival approximately 6 months . Refractory ascites occurs as a result of splanchnic vasodilatation and maximal activation of the sympathetic nervous system (SNS) and the renin - aldosterone system (RAAS) . The therapeutic options available for these patients are serial therapeutic paracentesis, liver transplantation and trans jugular intrahepatic portosystemic shunts .The model for end stage liver disease( MELD) score predicts survival in patients with cirrhosis . However, other factors in patients with cirrhosis and ascites are also associated with poor prognosis, including low mean arterial pressure; low serum sodium, low urine sodium, and high Child-Pugh score .
Read more
Variceal bleed is the most dreaded complication of cirrhosis and screening endoscopic is recommend in these patients. About 60% of patients with decompensated cirrhosis have varices at the time of diagnosis. Majority of these patients will require non selective beta blockers (NSBB) as standard of care as primary or secondary prophylaxis in prevention of variceal hemorrhage. NSBB reduce portal pressure by decreasing cardiac output and by producing splanchnic vasoconstriction.. Endoscopic variceal band ligation (EVL) is another modality of treatment of esophageal varices and meta-analysis showed EVL to be associated with significantly lower incidence of first variceal hemorrhage without differences in mortality compared to NSBB. NSBB also has shown to improve survival in these patients with nonhemodynamic effects. Some of the patients may progress to end stage liver disease characterized by the development of refractory ascites and other complications.
Most of the studies of NSBB comparing to EVL for primary/secondary prevention of variceal hemorrhage included patients of predominantly child A/B cirrhosis with variable number with ascites without any mention of ascites grading and some of trials excluded patient's with refractory ascites. These patients with ascites received diuretics and salt restricted diet as standard of care. However none of these studies mentioned about control of ascites and survival benefit in patients with advanced stage (child B and C) cirrhosis with ascites .In recent years the role of NSBB for prevention of variceal hemorrhage in refractory ascites patients has been questioned because of the deleterious effect on survival.However the use of NSBB in end stage liver disease has shown mixed results and controversial.
Therefore this study is being planned to know the effects of NSBB in advanced stage liver disease patients with ascites and varices in preventing variceal hemorrhage ,effect on ascites and survival.
- Conditions
- Ascites
- Being tested
- Propranolol, Endoscopic variceal ligation (EVL)
- Keywords
- Non selective beta blockers, Ascites
- Medical subject headings
- Ascites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Propranolol will be started at a dose of 40 mg and will be titrated based on pulse rate with target of 55-60 beats per minute or 20-25% reduction in heart rate and maximum tolerated dose.If any patients develop intolerable side effects, they will be withdrawn from the study
Endoscopic variceal ligation (EVL)Procedure or surgery
Patients in EVL group will undergo regular sessions of UGIE with EVL till variceal eradication every 2- 4 weekly followed by 3 monthly for initial 6 months and 6 monthly in rest of the study period. If any patient develop acute variceal hemorrhage on follow up , will be treated inpatient with standard medical therapy(SMT) .
| Study group | Role | What they receive |
|---|---|---|
| Propranolol | Active comparator | Propranolol will be started at a dose of 40 mg and will be titrated based on pulse rate with target of 55-60 beats per minute or 20-25% reduction in heart rate and maximum tolerated dose.If any patients develop intolerable side effects, they will be withdrawn from the study. Receives: Drug: Propranolol |
| Endoscopic variceal ligation (EVL) | Active comparator | Patients in EVL group will undergo regular sessions of UGIE with EVL till variceal eradication every 2- 4 weekly followed by 3 monthly for initial 6 months and 6 monthly in rest of the study period. If any patient develop acute variceal hemorrhage on follow up , will be treated inpatient with standard medical therapy (SMT) . Receives: Procedure: Endoscopic variceal ligation (EVL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
It is a categorical variable-patient dead/alive
Measured: Upto 48 weeks
Secondary outcomes (6)
Acute kidney injury (AKI)
Occurence of AKI will be noted in each group during 48 weeks follow up. The event, AKI is defined as Increase in sCr ≥0.3 mg/dl (≥26.5 μmol/L) within 48 hours; or,A percentage increase sCr ≥50% from baseline which is known, or presumed, to have occurred within the prior 7 days during study period. AKI will be treated accordingly.
Measured: Upto 48 weeks
Spontaneous bacterial peritonitis
The diagnosis is based on neutrophil count in ascitic fluid of >250/mm3 as determined by microscopy. Incidence will be noted at each follow up
Measured: 1 year
Hepatorenal syndrome( HRS)
HRS is defined as the occurrence of renal failure in a patient with advanced liver disease in the absence of an identifiable cause of renal failure. Criteria for the diagnosis include-
- Cirrhosis with ascites
- Serum creatinine >1.5 mg/dl (133 lmol/L)
- Absence of shock
- Absence of hypovolemia as defined by no sustained improvement of renal function (creatinine decreasing to <133 lmol/L) following at least 2 days of diuretic withdrawal (if on diuretics), and volume expansion with albumin at 1 g/kg/day up to a maximum of 100 g/day
- No current or recent treatment with nephrotoxic drugs
- Absence of parenchymal renal disease as defined by proteinuria <0.5 g/day, no microhaematuria (<50 red cells/high powered field), and normal renal ultrasonography.
Incidence of HRS will be noted at each follow up.
Measured: 1 year
Control of ascites
Control of ascites will be assesed by clinical examination in each follow up and response to therapy will be defined as follows:
- Complete Response - Elimination of ascites
- Partial Response- Presence of ascites not requiring paracentesis.
- Absence of response - Persistence of ascites requiring paracentesis
This parameter will be noted during follow up.
Measured: Upto 48 weeks
Incidence of variceal hemorrhage in each group
Occurence of variceal hemorrhage during follow up period will be noted
Measured: 1 year
Incidence of Paracentesis induced circulatory dysfunction (PICD) in different groups during LVP
PICD is defined as Increase in plasma renin activity of >50% of the pretreatment value on day 7 after each large volume paracentesis.
Measured: Upto 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2016 (estimated)
- Study start1 Jul 2015
- Primary completion30 Dec 2016
- Study completion30 Dec 2016
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 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
- None (open label)
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr.Virendra Singh, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Virendra Singh, MD,DM, Principal investigator, Professor of Hepatology,PGIMER,Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02649335
- Sponsor's protocol ID
- NSBB in cirrhotic ascites
- Acronym
- NSBB
- Status last verified
- May 2023
- First submitted
- 5 Dec 2015
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Singh V, Kumar P, Verma N, Vijayvergiya R, Singh A, Bhalla A. Propranolol vs. band ligation for primary prophylaxis of variceal hemorrhage in cirrhotic patients with ascites: a randomized controlled trial. Hepatol Int. 2022 Aug;16(4):944-953. doi: 10.1007/s12072-022-10361-4. Epub 2022 Jun 7.
PubMed 35672572
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites
- ClinicalTrials.gov ID
- NCT02649335
- Acronym / sponsor ID
- NSBB / NSBB in cirrhotic ascites
- Conditions
- Ascites
- Keywords
- Non selective beta blockers, Ascites
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 190 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 30 Dec 2016 (actual)
- Study completion
- 30 Dec 2016 (actual)
- First posted
- 7 Jan 2016 (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.
Cirrhosis is the leading cause of death in India and worldwide and leading causes in developed world include alcoholic liver disease, hepatitis C, and more recently, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH). As cirrhosis advances, portal hypertension develops, resulting in complications such as ascites, hepatic encephalopathy, and variceal hemorrhage.
Ascites is the most common major complication of cirrhosis, occurring in 50-60% of patients within ten years of diagnosis . Development of ascites is an ominous landmark in disease progression as 15% of patients with ascites will die within 1 year, and 44% within 5 years. Less than 10% patients develop refractory ascites and is associated with a poor prognosis with a high mortality, approximately 50% within 6 months and 75% at 1 year with the median survival approximately 6 months . Refractory ascites occurs as a result of splanchnic vasodilatation and maximal activation of the sympathetic nervous system (SNS) and the renin - aldosterone system (RAAS) . The therapeutic options available for these patients are serial therapeutic paracentesis, liver transplantation and trans jugular intrahepatic portosystemic shunts .The model for end stage liver disease( MELD) score predicts survival in patients with cirrhosis . However, other factors in patients with cirrhosis and ascites are also associated with poor prognosis, including low mean arterial pressure; low serum sodium, low urine sodium, and high Child-Pugh score .
Variceal bleed is the most dreaded complication of cirrhosis and screening endoscopic is recommend in these patients. About 60% of patients with decompensated cirrhosis have varices at the time of diagnosis. Majority of these patients will require non selective beta blockers (NSBB) as standard of care as primary or secondary prophylaxis in prevention of variceal hemorrhage. NSBB reduce portal pressure by decreasing cardiac output and by producing splanchnic vasoconstriction.. Endoscopic variceal band ligation (EVL) is another modality of treatment of esophageal varices and meta-analysis showed EVL to be associated with significantly lower incidence of first variceal hemorrhage without differences in mortality compared to NSBB. NSBB also has shown to improve survival in these patients with nonhemodynamic effects. Some of the patients may progress to end stage liver disease characterized by the development of refractory ascites and other complications.
Most of the studies of NSBB comparing to EVL for primary/secondary prevention of variceal hemorrhage included patients of predominantly child A/B cirrhosis with variable number with ascites without any mention of ascites grading and some of trials excluded patient's with refractory ascites. These patients with ascites received diuretics and salt restricted diet as standard of care. However none of these studies mentioned about control of ascites and survival benefit in patients with advanced stage (child B and C) cirrhosis with ascites .In recent years the role of NSBB for prevention of variceal hemorrhage in refractory ascites patients has been questioned because of the deleterious effect on survival.However the use of NSBB in end stage liver disease has shown mixed results and controversial.
Therefore this study is being planned to know the effects of NSBB in advanced stage liver disease patients with ascites and varices in preventing variceal hemorrhage ,effect on ascites and survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propranolol | Active comparator | Drug: PropranololPropranolol will be started at a dose of 40 mg and will be titrated based on pulse rate with target of 55-60 beats per minute or 20-25% reduction in heart rate and maximum tolerated dose.If any patients develop intolerable side effects, they will be withdrawn from the study. |
| Endoscopic variceal ligation (EVL) | Active comparator | Procedure: Endoscopic variceal ligation (EVL)Patients in EVL group will undergo regular sessions of UGIE with EVL till variceal eradication every 2- 4 weekly followed by 3 monthly for initial 6 months and 6 monthly in rest of the study period. If any patient develop acute variceal hemorrhage on follow up , will be treated inpatient with standard medical therapy (SMT) . |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Cirrhosis of any etiology with grade 2 ascites including refractory patients and varices/variceal hemorrhage requiring prophylaxis
- Cirrhosis diagnosed by clinical, analytical, and ultrasonographic findings or available histological findings
- Both inpatient and outpatient
- Child B or C status
Key exclusion criteria (9 listed)
- Active infection or recent infection < 2 weeks
- Hepatic encephalopathy grade 2 or higher
- Renal dysfunction at the time of inclusion
- Presence of hepatocellular carcinoma or portal vein thrombosis
- Active alcoholism
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 |
|---|---|---|
| PropranololPropranolol will be started at a dose of 40 mg and will be titrated based on pulse rate with target of 55-60 beats per minute or 20-25% reduction in heart rate and maximum tolerated dose.If any patients develop intolerable side effects, they will be withdrawn from the study | Drug | Propranolol |
| Endoscopic variceal ligation (EVL)Patients in EVL group will undergo regular sessions of UGIE with EVL till variceal eradication every 2- 4 weekly followed by 3 monthly for initial 6 months and 6 monthly in rest of the study period. If any patient develop acute variceal hemorrhage on follow up , will be treated inpatient with standard medical therapy(SMT) . | Procedure or surgery | Endoscopic variceal ligation (EVL) |
Primary outcome
Survival
Time frame: Upto 48 weeks
It is a categorical variable-patient dead/alive
6 secondary outcomes
Acute kidney injury (AKI)
Time frame: Upto 48 weeks
Spontaneous bacterial peritonitis
Time frame: 1 year
Hepatorenal syndrome( HRS)
Time frame: 1 year
Control of ascites
Time frame: Upto 48 weeks
Incidence of variceal hemorrhage in each group
Time frame: 1 year
Incidence of Paracentesis induced circulatory dysfunction (PICD) in different groups during LVP
Time frame: Upto 48 weeks
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 9 May 2023.
- Derived from this study: PubMed 35672572Singh V, Kumar P, Verma N, Vijayvergiya R, Singh A, Bhalla A. Propranolol vs. band ligation for primary prophylaxis of variceal hemorrhage in cirrhotic patients with ascites: a randomized controlled trial. Hepatol Int. 2022 Aug;16(4):944-953. doi: 10.1007/s12072-022-10361-4. Epub 2022 Jun 7.
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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.
Virendra Singh, MD,DM principal investigator
Professor of Hepatology,PGIMER,Chandigarh
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 Propranolol and Endoscopic variceal ligation (EVL) in people with Ascites, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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 9 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 9 May 2023. 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 India. 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.
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?
Survival (time frame: Upto 48 weeks). 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 NCT02649335, 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 9 May 2023; AzTrials last refreshed its copy on 6 Nov 2026.