Liver CirrhosisNCT07465471
Carvedilol and Midodrine Versus Carvedilol Alone in Preventing Early Rebleed in Patients With Cirrhosis.
A study testing Carvedilol and Midodrine Oral Product in people with Liver Cirrhosis, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Acute variceal bleeding (AVB) in cirrhosis occurs as a result of portal hypertension and carries a 6-week mortality rate of approximately 10-20%. Standard management includes a restrictive transfusion approach, vasoactive therapy, prophylactic antibiotics, and endoscopic band ligation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Carvedilol and Midodrine Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 1 siteIndia
- Study dates
- 1 Mar 2026to 30 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Consecutive patients of cirrhosis with high-risk acute variceal bleed (Child-Pugh class B > 7 with active bleeding at initial endoscopy or Child-Pugh class C < 14 points).
Who cannot join
- Age less than 18 years or > 75 years.
- HR < 60/ min and BP < 100/60 mm Hg
- Child-Pugh's score <8 and >13.
- MELD score >30 and serum lactate >12mmol/L.
- Refractory variceal bleed.
- Preemptive TIPS or previous Porto-systemic shunt or TIPS.
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- Non-selective Beta blocker/carvedilol / midodrine treatment in last 5 days.
- Acute kidney injury - HRS.
- Uncontrolled Hypertension (BP > 140/90 mmHg), heart block, congestive heart failure.
- Contraindication to NSBB (HR<60/min, BP<90/60mmHg, bronchial asthma).
- Hepatocellular carcinoma (outside Milan criteria), extrahepatic malignancy.
- Pregnant women.
- Bleeding from isolated gastric or ectopic varices.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site
Institute of Liver and Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
Dr Meenakshi Mann, DNB, 01146300000, meenakshimann22@gmail.com
About this study
Official title: Carvedilol and Midodrine Versus Carvedilol Alone in Preventing Early Rebleed in Patients With Cirrhosis: A Randomized Controlled Trial.
Acute variceal bleeding (AVB) in cirrhosis occurs as a result of portal hypertension and carries a 6-week mortality rate of approximately 10-20%. Standard management includes a restrictive transfusion approach, vasoactive therapy, prophylactic antibiotics, and endoscopic band ligation. Despite this, early rebleeding within the first 5 days still occurs in about 10-20% of patients, and individuals at particularly high risk may benefit from pre-emptive TIPS. However, its real-world use remains limited; one study reported that only 6.7% of eligible patients actually underwent pre-emptive TIPS, primarily due to logistical challenges and limited interventional radiology availability for early, non-emergent TIPS procedures.
Midodrine, an oral and fast-acting selective α1-adrenergic agonist, has been shown to enhance the effectiveness of nonselective beta-blockers like propranolol by allowing higher tolerated doses and achieving greater reductions in portal pressure (HVPG), thereby reducing the risk of initial variceal bleeding. However, no studies have evaluated the combination of midodrine with carvedilol-currently a preferred agent-versus carvedilol alone in patients at high risk of rebleeding.
To address this gap, we propose a study comparing carvedilol plus midodrine with carvedilol alone for preventing early rebleeding in cirrhotic patients. Individuals with cirrhosis (Child-Pugh 8-13) presenting with hematemesis will be enrolled, stabilized according to APASL guidelines, and after 48 hours randomized to either combined midodrine-carvedilol therapy or carvedilol alone. Participants will be followed for 6 weeks to assess the incidence of early rebleeding.
- Conditions
- Liver Cirrhosis
- Being tested
- Carvedilol, Midodrine Oral Product
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Carvedilol will be up-titrated by 3.125 mg daily to a maximum of 6.25 mg twice daily
Midodrine Oral ProductDrug
Midodrine will be increased by 5 mg daily to a maximum of 15 mg three times daily (45 mg/day).
| Study group | Role | What they receive |
|---|---|---|
| Midodrine+Carvedilol | Experimental | Patients in Group I will receive carvedilol 3.125 mg twice daily along with midodrine starting at 5 mg three times daily, with blood pressure monitored every 12 hours; carvedilol will be up-titrated by 3.125 mg daily to a maximum of 6.25 mg twice daily, and midodrine will be increased by 5 mg daily to a maximum of 15 mg three times daily (45 mg/day), aiming for the highest tolerated carvedilol dose without adverse effects such as systolic blood pressure falling below 90 mmHg Receives: Drug: Carvedilol; Drug: Midodrine Oral Product |
| Carvedilol | Active comparator | Group II will receive carvedilol alone, starting at 3.125 mg twice daily and titrated in the same manner as in Group I. Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with early variceal rebleed in 6 weeks in both the groups.
Measured: 6 weeks
Secondary outcomes (9)
Liver transplant free survival at 6 weeks.
Measured: 6 weeks
Blood products Transfusion at 6 weeks.
Measured: 6 weeks
Need of rescue therapy at 6 weeks (Danis Ella stent / Sengstaken tube/ rescue TIPS).
Measured: 6 weeks
Change in HVPG at 4 weeks.
Measured: 4 weeks
New decompensation and further decompensation at 6 weeks
Measured: 6 weeks
ICU stay and hospital stay duration.
Measured: 6 weeks
Change in MELD score
Measured: 6 weeks
Mean carvedilol dose in both groups at 6 weeks.
Measured: 6 weeks
Adverse events at 6 weeks
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2026
- Study start1 Mar 2026 (estimated)
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07465471
- Sponsor's protocol ID
- ILBS-Cirrhosis-76
- Status last verified
- Feb 2026
- First submitted
- 6 Mar 2026
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carvedilol and Midodrine Versus Carvedilol Alone in Preventing Early Rebleed in Patients With Cirrhosis: A Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT07465471
- Acronym / sponsor ID
- ILBS-Cirrhosis-76
- Conditions
- Liver Cirrhosis
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 1 Mar 2026 (estimated)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 12 Mar 2026 (actual)
- 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.
Acute variceal bleeding (AVB) in cirrhosis occurs as a result of portal hypertension and carries a 6-week mortality rate of approximately 10-20%. Standard management includes a restrictive transfusion approach, vasoactive therapy, prophylactic antibiotics, and endoscopic band ligation. Despite this, early rebleeding within the first 5 days still occurs in about 10-20% of patients, and individuals at particularly high risk may benefit from pre-emptive TIPS. However, its real-world use remains limited; one study reported that only 6.7% of eligible patients actually underwent pre-emptive TIPS, primarily due to logistical challenges and limited interventional radiology availability for early, non-emergent TIPS procedures.
Midodrine, an oral and fast-acting selective α1-adrenergic agonist, has been shown to enhance the effectiveness of nonselective beta-blockers like propranolol by allowing higher tolerated doses and achieving greater reductions in portal pressure (HVPG), thereby reducing the risk of initial variceal bleeding. However, no studies have evaluated the combination of midodrine with carvedilol-currently a preferred agent-versus carvedilol alone in patients at high risk of rebleeding.
To address this gap, we propose a study comparing carvedilol plus midodrine with carvedilol alone for preventing early rebleeding in cirrhotic patients. Individuals with cirrhosis (Child-Pugh 8-13) presenting with hematemesis will be enrolled, stabilized according to APASL guidelines, and after 48 hours randomized to either combined midodrine-carvedilol therapy or carvedilol alone. Participants will be followed for 6 weeks to assess the incidence of early rebleeding.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midodrine+Carvedilol | Experimental | Drug: Carvedilol, Drug: Midodrine Oral ProductPatients in Group I will receive carvedilol 3.125 mg twice daily along with midodrine starting at 5 mg three times daily, with blood pressure monitored every 12 hours; carvedilol will be up-titrated by 3.125 mg daily to a maximum of 6.25 mg twice daily, and midodrine will be increased by 5 mg daily to a maximum of 15 mg three times daily (45 mg/day), aiming for the highest tolerated carvedilol dose without adverse effects such as systolic blood pressure falling below 90 mmHg |
| Carvedilol | Active comparator | Drug: CarvedilolGroup II will receive carvedilol alone, starting at 3.125 mg twice daily and titrated in the same manner as in Group I. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Consecutive patients of cirrhosis with high-risk acute variceal bleed (Child-Pugh class B > 7 with active bleeding at initial endoscopy or Child-Pugh class C < 14 points).
Key exclusion criteria (13 listed)
- Age less than 18 years or > 75 years.
- HR < 60/ min and BP < 100/60 mm Hg
- Child-Pugh's score <8 and >13.
- MELD score >30 and serum lactate >12mmol/L.
- Refractory variceal bleed.
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 |
|---|---|---|
| CarvedilolCarvedilol will be up-titrated by 3.125 mg daily to a maximum of 6.25 mg twice daily | Drug | Carvedilol, Midodrine+Carvedilol |
| Midodrine Oral ProductMidodrine will be increased by 5 mg daily to a maximum of 15 mg three times daily (45 mg/day). | Drug | Midodrine+Carvedilol |
Primary outcome
Proportion of patients with early variceal rebleed in 6 weeks in both the groups.
Time frame: 6 weeks
9 secondary outcomes
Liver transplant free survival at 6 weeks.
Time frame: 6 weeks
Blood products Transfusion at 6 weeks.
Time frame: 6 weeks
Need of rescue therapy at 6 weeks (Danis Ella stent / Sengstaken tube/ rescue TIPS).
Time frame: 6 weeks
Change in HVPG at 4 weeks.
Time frame: 4 weeks
New decompensation and further decompensation at 6 weeks
Time frame: 6 weeks
ICU stay and hospital stay duration.
Time frame: 6 weeks
Change in MELD score
Time frame: 6 weeks
Mean carvedilol dose in both groups at 6 weeks.
Time frame: 6 weeks
Adverse events at 6 weeks
Time frame: 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2026.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carvedilol and Midodrine Oral Product in people with Liver Cirrhosis, run by Institute of Liver and Biliary Sciences, India 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 1 inclusion and 13 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: opening soon, as of the sponsor's last update on 12 Mar 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr Meenakshi S Mann, DNB (01146300000, meenakshimann22@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with early variceal rebleed in 6 weeks in both the groups. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Mar 2026.