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.

Inclusion Criteria:

1. 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:

1. Age less than 18 years or > 75 years.
2. HR < 60/ min and BP < 100/60 mm Hg
3. Child-Pugh's score <8 and >13.
4. MELD score >30 and serum lactate >12mmol/L.
5. Refractory variceal bleed.
6. Preemptive TIPS or previous Porto-systemic shunt or TIPS.
7. Non-selective Beta blocker/carvedilol / midodrine treatment in last 5 days.
8. Acute kidney injury - HRS.
9. Uncontrolled Hypertension (BP > 140/90 mmHg), heart block, congestive heart failure.
10. Contraindication to NSBB (HR<60/min, BP<90/60mmHg, bronchial asthma).
11. Hepatocellular carcinoma (outside Milan criteria), extrahepatic malignancy.
12. Pregnant women.
13. Bleeding from isolated gastric or ectopic varices.