Apixaban-PK Trial: Preventing 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
Asian Institute Of Medical Sciences
220 participants
Apr 1, 2026
INTERVENTIONAL
Conditions
Summary
The APIXABAN-PK trial is a prospective, randomized, single-blind, placebo-controlled study designed to evaluate the efficacy and safety of apixaban in combination with carvedilol versus placebo with carvedilol in preventing portal hypertension-related complications in patients with cirrhosis. Conducted at the Gastroenterology and Hepatology Department and Clinical Trials Unit (CTU) of Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan, the trial will enroll eligible cirrhotic patients with portal hypertension. Participants will be followed for 12 months to monitor hepatic decompensation events, variceal bleeding, portal vein thrombosis, and mortality, while safety and tolerability of apixaban will be closely assessed. This study aims to provide local evidence for apixaban use in cirrhosis management in Pakistan.
Eligibility
Inclusion Criteria6
- Adults aged ≥18 years with diagnosed cirrhosis (any etiology), confirmed by histology, transient elastography (≥12.5 kPa), or consistent clinical/imaging findings.
- Evidence of portal hypertension, defined by:
- Clinical: presence of varices on endoscopy, ascites, or splenomegaly with thrombocytopenia.
- 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.
- 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.
- Able to provide informed consent and comply with study procedures.
Exclusion Criteria15
- Active gastrointestinal bleeding within 6 weeks prior to enrollment.
- 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
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²) or on dialysis.
- Child-Pugh class C or Child-Pugh score ≥10.
- History of hypersensitivity to apixaban or carvedilol.
- Pregnancy, breastfeeding, or unwillingness to use effective contraception during the study period.
- 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.
- Use of NSAIDs, SSRIs, or other medications that significantly increase bleeding risk, unless approved by the PI with clear risk-benefit justification.
- Active hepatocellular carcinoma (HCC) outside Milan criteria or with vascular invasion.
- Current or planned liver transplantation.
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Interventions
Apixaban 2.5 mg oral tablet taken twice daily for 12 months. Apixaban is a direct factor Xa inhibitor that blocks thrombin generation and clot formation through inhibition of the coagulation cascade. Dose adjustment: continue 2.5 mg twice daily if eGFR ≥30 mL/min/1.73 m²; if eGFR 15-29 mL/min/1.73 m², continue with close monitoring; if eGFR \<15 mL/min/1.73 m², discontinue. Withheld in case of major bleeding or severe hepatic decompensation.
Carvedilol oral tablet titrated according to protocol-defined schedule. Initiated at 6.25 mg once daily at baseline. Titrated every 2-4 weeks based on heart rate and blood pressure: 6.25 mg twice daily at week 2, 12.5 mg twice daily at week 4, with target maintenance dose of 12.5 mg twice daily. Dose may be reduced or withheld if heart rate \<55 bpm, systolic blood pressure \<90 mmHg, or symptomatic hypotension develops.
Placebo oral tablet matching apixaban in appearance, taken twice daily for 12 months. No active ingredient.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07521332