Apixaban plus carvedilol to prevent portal-hypertension complications in cirrhosis

Apixaban Plus Carvedilol to Prevent Portal Hypertension Complications in Cirrhosis: A Randomized Single-Blind Placebo-Controlled Trial at AIMS, Hyderabad, Pakistan

This will test whether adding apixaban to carvedilol can help prevent variceal bleeding, portal vein thrombosis, and other portal-hypertension complications in adults with Child-Pugh B cirrhosis.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Asian Institute Of Medical Sciences (Academic / other)
• Locations: 1 site (Hyderābād, Sindh)
• Trial ID: NCT07521332 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, single-blind, placebo-controlled Phase 4 trial at the Asian Institute of Medical Sciences in Hyderabad, Pakistan. Eligible adults with cirrhosis and portal hypertension (Child-Pugh B, 7–10) are randomized 1:1 to apixaban 2.5 mg twice daily plus carvedilol (titrated per protocol) or matching placebo plus the same carvedilol regimen. Participants are followed for 12 months with visits at baseline, 1, 3, 6, 9, and 12 months and an early safety check at 2 weeks, tracking hepatic decompensation events, variceal bleeding, portal vein thrombosis, mortality, and safety/tolerability. High-risk varices are treated with band ligation to obliteration before randomization and safety monitoring for bleeding is emphasized throughout the study.

Who should consider this trial

Good fit: Adults (≥18 years) with confirmed cirrhosis and evidence of portal hypertension, generally Child-Pugh B (score 7–10), who can undergo recent EGD and tolerate carvedilol are ideal candidates.

Not a fit: Patients with recent active gastrointestinal bleeding, very high bleeding risk (for example platelet count <50,000/µL), or those with more advanced or unstable liver disease are unlikely to benefit and are excluded.

Why it matters

Potential benefit: If successful, adding apixaban could lower rates of variceal bleeding, portal vein thrombosis, and other liver-related complications, potentially reducing hospitalizations and deaths.

How similar studies have performed: Prior small observational studies and some randomized data on anticoagulants in cirrhosis suggest DOACs can reduce portal vein thrombosis and may be safe in selected patients, but large randomized trials combining DOACs with carvedilol are limited.

Eligibility criteria

Inclusion Criteria:

1. Adults aged ≥18 years with diagnosed cirrhosis (any etiology), confirmed by histology, transient elastography (≥12.5 kPa), or consistent clinical/imaging findings.
2. Evidence of portal hypertension, defined by:

   Clinical: presence of varices on endoscopy, ascites, or splenomegaly with thrombocytopenia.
3. Compensated or early decompensated cirrhosis (Child-Pugh B 7-10), with stable liver function defined as no change in Child-Pugh score \>1 point in the preceding 3 months.
4. Screening esophagogastroduodenoscopy (EGD) performed within 6 months prior to enrollment. Patients with high-risk varices (large varices, red wale signs, or history of variceal bleeding) must undergo endoscopic variceal band ligation to obliteration before randomization.
5. Able to provide informed consent and comply with study procedures.

Exclusion Criteria:

1. Active gastrointestinal bleeding within 6 weeks prior to enrollment.
2. High bleeding risk:

   * Platelet count \<50,000/µL at baseline
   * INR \>1.8 (or \>2.0 if secondary to cirrhosis without additional coagulopathy)
   * Active peptic ulcer disease
   * History of intracranial hemorrhage or hemorrhagic stroke
   * Known bleeding diathesis
3. Severe renal impairment (eGFR \< 30 mL/min/1.73 m²) or on dialysis.
4. Child-Pugh class C or Child-Pugh score ≥10.
5. History of hypersensitivity to apixaban or carvedilol.
6. Pregnancy, breastfeeding, or unwillingness to use effective contraception during the study period.
7. Concurrent anticoagulant or antiplatelet therapy (including aspirin, clopidogrel, warfarin, or other DOACs) that cannot be safely discontinued. A washout period of at least 5 half-lives is required before randomization.
8. Use of NSAIDs, SSRIs, or other medications that significantly increase bleeding risk, unless approved by the PI with clear risk-benefit justification.
9. Active hepatocellular carcinoma (HCC) outside Milan criteria or with vascular invasion.
10. Current or planned liver transplantation.

Where this trial is running

Hyderābād, Sindh

• Asian Institute of Medical Sciences — Hyderābād, Sindh, Pakistan (Recruiting)

Study contacts

• Principal investigator: Sadik Memon, MBBS,MRCP,FCPS — Asian Institute Of Medical Sciences
• Study coordinator: Fatima Nadeem Dr, Pharm-D, Mphil

Conditions Cirrhosis; Esophageal and Gastric Varices; Ascites; Hepatic Encephalopathy; Portal Vein Thrombosis; Portal Hypertension; apixaban; carvedilol