Carvedilol and Midodrine Versus Carvedilol Alone in Preventing Early Rebleed in Patients With Cirrhosis.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Carvedilol, Midodrine Oral Product.
- Who it may be relevant to
- Registry conditions: Liver Cirrhosis. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- India
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Carvedilol and Midodrine Versus Carvedilol Alone in Preventing Early Rebleed in Patients With Cirrhosis: A Randomized Controlled Trial.
Overview
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.
Interventions
- Drug Carvedilol
Carvedilol will be up-titrated by 3.125 mg daily to a maximum of 6.25 mg twice daily - Drug Midodrine Oral Product
Midodrine will be increased by 5 mg daily to a maximum of 15 mg three times daily (45 mg/day).
Primary outcome measures
- Proportion of patients with early variceal rebleed in 6 weeks in both the groups. [Time frame: 6 weeks]
Secondary outcome measures (9)
- 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]
Eligibility criteria
Inclusion criteria
- 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).
Exclusion criteria
- 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.
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
India · 1 center
- Institute of Liver and Biliary Sciences — New Delhi
Identifiers
NCT: NCT07465471 · ILBS-Cirrhosis-76