Apixaban-PK Trial: Preventing Portal Hypertension Complications in Cirrhosis

NCT07521332 | Recruiting Phase 4 DMC

• 1 other identifier: AIMS/ERC/9853/26
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

apixaban; carvedilol; cirrhosis; portal hypertension; direct oral anticoagulant; variceal bleeding; hepatic decompensation; portal vein thrombosis; randomized controlled trial; Pakistan; Factor Xa Inhibitor; non-selective beta-blocker; prevention; liver disease

Outcome Measures

Primary Outcomes (1)

• First Occurrence of Portal Hypertension-Related Complications

  Time to first occurrence of a composite of portal hypertension-related complications, defined as variceal bleeding, ascites, hepatic encephalopathy, portal vein thrombosis, or liver-related death, within 12 months of randomization.

  12 months

Secondary Outcomes (1)

• Major and Minor Bleeding Events

  12 months

Study Arms (2)

Intervention Group: Apixaban + Carvedilol

EXPERIMENTAL

Apixaban, Carvedilol

Drug: Apixaban; Drug: Carvedilol

Control Group: Placebo + Carvedilol

PLACEBO COMPARATOR

Placebo, Carvedilol

Drug: Carvedilol; Drug: Placebo

Interventions

Apixaban DRUG

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.

Intervention Group: Apixaban + Carvedilol

Carvedilol DRUG

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.

Control Group: Placebo + Carvedilol; Intervention Group: Apixaban + Carvedilol

Placebo DRUG

Placebo oral tablet matching apixaban in appearance, taken twice daily for 12 months. No active ingredient.

Control Group: Placebo + Carvedilol

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Asian Institute Of Medical Sciences: lead

Study Sites (1)

Asian Institute of Medical Sciences

Hyderābād, Sindh, 71000, Pakistan

RECRUITING

Related Publications (7)

• Simon TG,Singer DE,Zhang Y,Mastrorilli JM,Cervone A,DiCesare E,Lin KJ

  BACKGROUND

• Xu PS,Wang MC,Chen JJ,Wang HY

  BACKGROUND

• Brown RS,Brown KA,Flamm S,Bejarano RE,Rahimi RS,Singal AK,Rockey DC

  BACKGROUND

• Nulan Y,Felli E,Selicean SE,Prampolini M,Berzigotti A,Gracia-Sancho J,Bosch J

  BACKGROUND

• Mullarkey MJ,Ogola GO,Asrani SK,Volk ML

  BACKGROUND

• Süffert LC,de Faria Moraes B,Cançado GGL

  BACKGROUND

• Joshi A,Raja HAA,Roy P,Latif F,Reji RG,Deb N,Mui RK,Shady A

  BACKGROUND

Related Links

• Official NCI CTCAE v6.0 criteria for adverse event grading and documentation.

MeSH Terms

Conditions

Fibrosis; Esophageal and Gastric Varices; Ascites; Hepatic Encephalopathy; Hypertension, Portal; Liver Diseases

Interventions

apixaban; Carvedilol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

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

Study Officials

• Sadik Memon, MBBS,MRCP,FCPS

  Asian Institute Of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Dr. Fatima Nadeem, Pharm-D, Mphil

  Asian Institute Of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Fatima Nadeem Dr, Pharm-D, Mphil

CONTACT

+923080744996; fatima.nadeem2401@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a single-blind study. Participants are blinded to treatment allocation and receive either apixaban or an identical-appearing placebo. Investigators and pharmacy personnel are not blinded and are aware of the assigned treatment. The allocation list is secured at the Clinical Trials Unit (CTU) and accessible only to authorized unblinded personnel. Masked Parties: Participants (blinded) Outcome assessors (blinded to treatment allocation during outcome adjudication) Data Safety Monitoring Board (DSMB) members (receive unblinded safety data as per DSMB charter) Data analysts (may remain blinded until final analysis per statistical analysis plan) Unmasked Parties: Principal Investigator Co-Principal Investigator / Pharmacy and Drug Accountability Officer Pharmacy personnel responsible for dispensing study medication Unblinding: Unblinding is permitted only in medical emergencies when knowledge of the treatment assignment is necessary for participant management.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr.

Model Details: This is a prospective, randomized, single-blind, placebo-controlled trial with parallel assignment. Eligible participants with cirrhosis and portal hypertension (Child-Pugh A or B ≤9) are randomized 1:1 to two arms. Intervention Arm: apixaban 2.5 mg twice daily plus carvedilol titrated to 12.5 mg twice daily. Control Arm: matching placebo twice daily plus carvedilol titrated identically. Randomization uses a computer-generated sequence with permuted blocks; allocation is concealed via centralized web-based system accessible only to unblinded pharmacist. Participants are blinded; investigators and pharmacy personnel are unblinded. All participants are followed 12 months with visits at baseline, 2 weeks (safety call), and 1, 3, 6, 9, and 12 months. Analysis is intention-to-treat. An independent DSMB reviews unblinded safety data after 50% of participants complete 6 months, with predefined stopping rules for excessive bleeding or mortality.

Study Record Dates

• First Submitted: March 31, 2026
• First Posted: April 9, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)