Carvedilol and Midodrine Versus Carvedilol Alone in Preventing Early Rebleed in Patients With Cirrhosis.

NCT07465471 | Not Yet Recruiting

• 1 other identifier: ILBS-Cirrhosis-76
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with early variceal rebleed in 6 weeks in both the groups.

  6 weeks

Secondary Outcomes (9)

• Liver transplant free survival at 6 weeks.

  6 weeks

• Blood products Transfusion at 6 weeks.

  6 weeks

• Need of rescue therapy at 6 weeks (Danis Ella stent / Sengstaken tube/ rescue TIPS).

  6 weeks

• Change in HVPG at 4 weeks.

  4 weeks

• New decompensation and further decompensation at 6 weeks

  6 weeks

Study Arms (2)

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

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.

Drug: Carvedilol

Interventions

Carvedilol DRUG

Carvedilol will be up-titrated by 3.125 mg daily to a maximum of 6.25 mg twice daily

Carvedilol; Midodrine+Carvedilol

Midodrine Oral Product DRUG

Midodrine will be increased by 5 mg daily to a maximum of 15 mg three times daily (45 mg/day).

Midodrine+Carvedilol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Central Study Contacts

Dr Meenakshi S Mann, DNB

CONTACT

01146300000; meenakshimann22@gmail.com

Dr Chitranshu Vashishtha, DM

CONTACT

01146300000; chitranshuv@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2026
• First Posted: March 12, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-02

Locations

IN (1)