Acute on Chronic Liver FailureNCT07422948
Efficacy and Safety of Early Initiation of Midodrine for Control and Prevention of Ascites and Its Related Complications in Acute-on-chronic Liver Failure.
A study testing Midodrine and Standard Medical Treatment in people with Acute on Chronic Liver Failure, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Ascites is a cardinal and debilitating complication in patients with acute-on-chronic liver failure (ACLF), significantly correlating with disease severity and poor prognosis. The underlying pathophysiology is driven by severe splanchnic arterial vasodilation, which reduces effective arterial blood volume and triggers… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute on Chronic Liver Failure
- What is being tested?
- Midodrine and Standard Medical Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 1 siteIndia
- Study dates
- 5 Feb 2026to 30 Aug 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- ACLF
- Ascites (Grade II/III).
- Willing/able for salt restriction, labs, urine collections, and follow-ups; consent obtained.
Who cannot join
- SCr ≥ 1.5 mg/dL OR ongoing AKI >stage I
- Persistent or uncorrectable severe hyponatremia (Na ≤120 mEq/L), hyperkalemia (>6.0 mEq/L) or any other critical electrolyte imbalance.
- Refractory ascites
- Spontaneous bacterial peritonitis
- Hepatic encephalopathy grade II-III.
- Shock, need for IV vasopressors, SBP <90 mmHg or MAP <65 despite fluids/albumin.
Show all 12Show fewer
- Active GI bleed, uncontrolled infection/sepsis, or SBP at screening.
- Severe cardiomyopathy, critical valvular disease, arrhythmias contraindicating α-agonists.
- ACLF patients on Mechanical ventilation/ICU/ionotropes/High flow oxygen
- Pregnancy, lactation.
- Hypersensitivity/intolerance to midodrine.
- Significant LUTS.
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 Chunnee Zangmu Bhutia, 01146300000, czb.cr7@gmail.com
About this study
Official title: Efficacy and Safety of Early Initiation of Midodrine for Control and Prevention of Ascites and Its Related Complications in Acute-on-chronic Liver Failure: A Randomized Controlled Trial.
Ascites is a cardinal and debilitating complication in patients with acute-on-chronic liver failure (ACLF), significantly correlating with disease severity and poor prognosis. The underlying pathophysiology is driven by severe splanchnic arterial vasodilation, which reduces effective arterial blood volume and triggers compensatory neurohumoral activation. This cascade leads to profound sodium retention, renal vasoconstriction, and circulatory instability. Consequently, patients with ACLF frequently experience diuretic intolerance and are at elevated risk for severe complications, including electrolyte disturbances, acute kidney injury (AKI), and hepatorenal syndrome (HRS).
Current management strategies rely heavily on diuretics and albumin; however, the efficacy of diuretics is often limited by systemic hypotension and pre-existing renal impairment, leading to frequent treatment failure or diuretic-induced complications. Existing clinical guidelines lack definitive recommendations regarding the preemptive use of vasoconstrictors to stabilize hemodynamics before ascites becomes refractory. Midodrine, an oral alpha-1 adrenergic agonist, targets this circulatory dysfunction by increasing systemic vascular resistance and improving renal perfusion. This randomized controlled trial aims to evaluate the efficacy and safety of the early initiation of midodrine in achieving better control of ascites and preventing the progression to renal complications in patients with acute-on-chronic liver failure.
- Conditions
- Acute on Chronic Liver Failure
- Being tested
- Midodrine, Standard Medical Treatment
- Medical subject headings
- Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidodrineDrug
Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.
Standard Medical TreatmentOther
- Sodium restriction to ≤5 g/day.
- Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose.
- Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop.
- Other supportive measures: as per the clinician
- Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management.
- IV albumin during LVP
- Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections.
- Correction of electrolytes and renal support as needed.
- Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).
| Study group | Role | What they receive |
|---|---|---|
| Midodrine+SMT | Experimental | 1. Sodium restriction to ≤5 g/day.
2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose.
a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop.
3. Other supportive measures: as per the clinician
1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management.
2. IV albumin during LVP
3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections.
4. Correction of electrolytes and renal support as needed.
5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).
4. Midodrine: Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS. Receives: Drug: Midodrine; Other: Standard Medical Treatment |
| Placebo+SMT | Active comparator | 1. Sodium restriction to ≤5 g/day.
2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose.
a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop.
3. Other supportive measures: as per the clinician
1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management.
2. IV albumin during LVP
3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections.
4. Correction of electrolytes and renal support as needed.
5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).
4. Placebo Receives: Other: Standard Medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with no ascites between the two groups at day 28.
Measured: Day 28
Secondary outcomes (23)
Percentage of patients with no ascites
Measured: Day 7 & 14
Partial ascites response
Measured: 7,14,28 days
Absent response or worsening of ascites
Measured: 28 day
Large Volume Paracentesis requirement in two groups
Measured: day 7 and 28
Cumulative dose of diuretics/Albumin/midodrine/carvedilol
Measured: day 28
Change in Intra Abdominal pressure measured by manometer between both groups
Measured: Day 7
Change in MAP between both groups.
Measured: 7 days, then day 14 and 28
Change in Weight change between both groups.
Measured: 7 days, then day 14 and 28
Change in urine output daily between both groups
Measured: 7 days, then day 14 and 28
Change in HR between both groups
Measured: 7 days, then day 14 and 28
Change in urine Na
Measured: day 3, 7 and 28 from baseline
Change in MELD score between both groups.
Measured: day 4, 7 and 28
Change in AARC score between both groups.
Measured: day 4, 7 and 28
Reduction in Hepatic Venous Pressure Gradient between both groups.
Measured: 14 and 28 days.
Mortality
Measured: day 28
New onset AKI between both groups.
Measured: day 28
New onset SBP between both groups
Measured: day 28
New onset AKI, SBP, HE, Hyponatremia, shock and need for MV
Measured: day 28
New onset HE between both groups
Measured: day 28
New onset Hyponatremia between both groups.
Measured: day 28
New onset shock between both groups.
Measured: day 28
New onset need for MV between both groups
Measured: day 28
Treatment related adverse effects
Measured: day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start5 Feb 2026 (estimated)
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute on Chronic Liver FailureStudies 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
- None (open label)
- Enrolment
- 113 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
- NCT07422948
- Sponsor's protocol ID
- ILBS-ACLF-26
- Status last verified
- Jan 2026
- First submitted
- 29 Jan 2026
- Last updated
- 20 Feb 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 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Early Initiation of Midodrine for Control and Prevention of Ascites and Its Related Complications in Acute-on-chronic Liver Failure: A Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT07422948
- Acronym / sponsor ID
- ILBS-ACLF-26
- Conditions
- Acute on Chronic Liver Failure
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 113 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 5 Feb 2026 (estimated)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Aug 2027 (estimated)
- First posted
- 20 Feb 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.
Ascites is a cardinal and debilitating complication in patients with acute-on-chronic liver failure (ACLF), significantly correlating with disease severity and poor prognosis. The underlying pathophysiology is driven by severe splanchnic arterial vasodilation, which reduces effective arterial blood volume and triggers compensatory neurohumoral activation. This cascade leads to profound sodium retention, renal vasoconstriction, and circulatory instability. Consequently, patients with ACLF frequently experience diuretic intolerance and are at elevated risk for severe complications, including electrolyte disturbances, acute kidney injury (AKI), and hepatorenal syndrome (HRS).
Current management strategies rely heavily on diuretics and albumin; however, the efficacy of diuretics is often limited by systemic hypotension and pre-existing renal impairment, leading to frequent treatment failure or diuretic-induced complications. Existing clinical guidelines lack definitive recommendations regarding the preemptive use of vasoconstrictors to stabilize hemodynamics before ascites becomes refractory. Midodrine, an oral alpha-1 adrenergic agonist, targets this circulatory dysfunction by increasing systemic vascular resistance and improving renal perfusion. This randomized controlled trial aims to evaluate the efficacy and safety of the early initiation of midodrine in achieving better control of ascites and preventing the progression to renal complications in patients with acute-on-chronic liver failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midodrine+SMT | Experimental | Drug: Midodrine, Other: Standard Medical Treatment1. Sodium restriction to ≤5 g/day. 2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose. a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop. 3. Other supportive measures: as per the clinician 1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management. 2. IV albumin during LVP 3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections. 4. Correction of electrolytes and renal support as needed. 5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.). 4. Midodrine: Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS. |
| Placebo+SMT | Active comparator | Other: Standard Medical Treatment1. Sodium restriction to ≤5 g/day. 2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose. a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop. 3. Other supportive measures: as per the clinician 1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management. 2. IV albumin during LVP 3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections. 4. Correction of electrolytes and renal support as needed. 5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.). 4. Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years.
- ACLF
- Ascites (Grade II/III).
- Willing/able for salt restriction, labs, urine collections, and follow-ups; consent obtained.
Key exclusion criteria (12 listed)
- SCr ≥ 1.5 mg/dL OR ongoing AKI >stage I
- Persistent or uncorrectable severe hyponatremia (Na ≤120 mEq/L), hyperkalemia (>6.0 mEq/L) or any other critical electrolyte imbalance.
- Refractory ascites
- Spontaneous bacterial peritonitis
- Hepatic encephalopathy grade II-III.
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 |
|---|---|---|
| MidodrineStart with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS. | Drug | Midodrine+SMT |
| Standard Medical Treatment1. Sodium restriction to ≤5 g/day. 2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose. a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop. 3. Other supportive measures: as per the clinician 1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management. 2. IV albumin during LVP 3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections. 4. Correction of electrolytes and renal support as needed. 5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.). | Other | Midodrine+SMT, Placebo+SMT |
Primary outcome
Proportion of patients with no ascites between the two groups at day 28.
Time frame: Day 28
23 secondary outcomes
Percentage of patients with no ascites
Time frame: Day 7 & 14
Partial ascites response
Time frame: 7,14,28 days
Absent response or worsening of ascites
Time frame: 28 day
Large Volume Paracentesis requirement in two groups
Time frame: day 7 and 28
Cumulative dose of diuretics/Albumin/midodrine/carvedilol
Time frame: day 28
Change in Intra Abdominal pressure measured by manometer between both groups
Time frame: Day 7
Change in MAP between both groups.
Time frame: 7 days, then day 14 and 28
Change in Weight change between both groups.
Time frame: 7 days, then day 14 and 28
Change in urine output daily between both groups
Time frame: 7 days, then day 14 and 28
Change in HR between both groups
Time frame: 7 days, then day 14 and 28
Change in urine Na
Time frame: day 3, 7 and 28 from baseline
Change in MELD score between both groups.
Time frame: day 4, 7 and 28
Change in AARC score between both groups.
Time frame: day 4, 7 and 28
Reduction in Hepatic Venous Pressure Gradient between both groups.
Time frame: 14 and 28 days.
Mortality
Time frame: day 28
New onset AKI between both groups.
Time frame: day 28
New onset SBP between both groups
Time frame: day 28
New onset AKI, SBP, HE, Hyponatremia, shock and need for MV
Time frame: day 28
New onset HE between both groups
Time frame: day 28
New onset Hyponatremia between both groups.
Time frame: day 28
New onset shock between both groups.
Time frame: day 28
New onset need for MV between both groups
Time frame: day 28
Treatment related adverse effects
Time frame: day 28
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 20 Feb 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 Midodrine and Standard Medical Treatment in people with Acute on Chronic Liver Failure, 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 4 inclusion and 12 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 20 Feb 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 Chunnee Zangmu Bhutia, MD (01146300000, czb.cr7@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 no ascites between the two groups at day 28. (time frame: Day 28). 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 20 Feb 2026.