NCT07521332

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

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 220 (estimated)
• Sponsor: Asian Institute Of Medical Sciences · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The APIXABAN-PK trial is a prospective, randomized, single-blind, placebo-controlled study conducted at the Asian Institute of Medical Sciences (AIMS) Hospital in Hyderabad, Pakistan. The study aims to evaluate the efficacy and safety of apixaban, a direct factor Xa inhibitor, in combination with carvedilol compared to carvedilol alone (with placebo) for preventing portal hypertension-related complications in patients with cirrhosis. Patients with confirmed cirrhosis and evidence of portal hypertension (Child-Pugh B 7-10) are eligible. Participants undergo screening, including esophagogastroduodenoscopy (EGD) within six months prior to enrollment. Those with high-risk varices receive endoscopic variceal band ligation to obliteration before randomization to ensure baseline safety. Eligible participants are randomized in a 1:1 ratio to one of two groups: Intervention Group: Apixaban 2.5 mg orally twice daily plus carvedilol (titrated according to a protocol-defined schedule). Control Group: Placebo (matching apixaban) orally twice daily plus carvedilol (titrated according to the same schedule). Carvedilol is initiated at 6.25 mg once daily and titrated every 2-4 weeks based on heart rate and blood pressure, aiming for a maintenance dose of 12.5 mg twice daily, as tolerated. Dose adjustments are made for hypotension or bradycardia. All participants are followed for 12 months. Study visits occur at baseline, 2 weeks (safety telephone call), and 1, 3, 6, 9, and 12 months. Assessments include vital signs, laboratory tests (complete blood count, liver and renal function, international normalized ratio), and imaging (abdominal ultrasound with Doppler and transient elastography at specified intervals). Adherence is monitored via pill counts and patient diaries. The primary outcome is the first occurrence of portal hypertension-related complications (variceal bleeding, ascites, hepatic encephalopathy, portal vein thrombosis, or liver-related death) within 12 months. Secondary outcomes include bleeding events (major and minor), time to first decompensation or hospitalization, all-cause and liver-related mortality, and changes in non-invasive markers of portal hypertension (e.g., liver stiffness, platelet count). Safety is closely monitored through routine assessments and an independent Data Safety Monitoring Board (DSMB). The DSMB reviews unblinded safety data after 50% of participants have completed 6 months of follow-up, with predefined stopping rules for excessive bleeding or mortality. Adverse events are graded using CTCAE v6.0 criteria. Statistical analysis will be performed on an intention-to-treat basis. The primary endpoint (time to first complication) will be analyzed using Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazards regression. The study aims to enroll 220 participants to account for anticipated dropout, with 100 participants per arm required to detect a 50% relative risk reduction in the primary outcome (two-sided α = 0.05, power = 80%). Enrollment is planned over 12 months, with a total study duration of 24 months. This investigator-initiated trial is sponsored by the Asian Institute of Medical Sciences and is registered on ClinicalTrials.gov. Results will be submitted for publication within 12 months of study completion, regardless of outcome, in accordance with ICMJE guidelines.

Conditions

• Cirrhosis
• Esophageal and Gastric Varices
• Ascites
• Hepatic Encephalopathy
• Portal Vein Thrombosis
• Portal Hypertension

Interventions

Type	Name	Description
DRUG	Apixaban	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.
DRUG	Carvedilol	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.
DRUG	Placebo	Placebo oral tablet matching apixaban in appearance, taken twice daily for 12 months. No active ingredient.

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-04-01
• Completion: 2028-04-01
• First posted: 2026-04-09
• Last updated: 2026-04-09

Locations

1 site across 1 country: Pakistan