A Phase 4 interventional study of Apixaban and Carvedilol in Cirrhosis, Esophageal and Gastric Varices and Ascites, sponsored by Asian Institute Of Medical Sciences. Recruiting at 1 site in Pakistan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-09.
Sponsored by Asian Institute Of Medical Sciences · Phase 4, Interventional, and Prevention
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.
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.
150 studies on the registry are indexed under Esophageal and Gastric Varices; 39 are open to participants now.
This study's planned enrollment of 220 is above the median of 110 across 96 interventional studies indexed under Esophageal and Gastric Varices.
Browse Esophageal and Gastric Varices studies →Asian Institute Of Medical Sciences is the lead sponsor of 3 studies on the registry; 2 are open to participants now.
Compared within Esophageal and Gastric Varices, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Fibrosis. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Evidence of portal hypertension, defined by:
Clinical: presence of varices on endoscopy, ascites, or splenomegaly with thrombocytopenia.
Exclusion Criteria:
High bleeding risk:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Apixaban, Carvedilol
Drug: Apixaban · Drug: Carvedilol
Placebo, Carvedilol
Drug: Carvedilol · Drug: Placebo
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.
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.
Time frame: 12 months
Major and Minor Bleeding Events
Incidence of major and minor bleeding events attributable to apixaban in combination with carvedilol. Major bleeding is defined by ISTH criteria (fatal bleeding, symptomatic bleeding in a critical area, bleeding causing a fall in hemoglobin ≥2 g/dL, or requiring transfusion of ≥2 units of packed red blood cells). Minor bleeding is defined as any overt bleeding not meeting major criteria.
Time frame: 12 months
Plan to share: No — IPD will not be shared because: This is a single-center investigator-initiated trial without infrastructure for external data sharing The protocol and informed consent do not include provisions for sharing IPD with external researchers Institutional policy does not support IPD sharing for this study Aggregate results will be published per ICMJE guidelines
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Studies of the drug tested here: Apixaban
Esophageal and Gastric Varices →
Asian Institute Of Medical Sciences