Apixaban Plus Carvedilol to Prevent Portal Hypertension Complications in Cirrhosis: A Randomized Single-Blind Placebo-Controlled Trial at AIMS, Hyderabad, Pakistan
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- First Occurrence of Portal Hypertension-Related Complications
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 ≥
- •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.
研究组 & 干预措施
Intervention Group: Apixaban + Carvedilol
Apixaban, Carvedilol
干预措施: Carvedilol (Drug)
Control Group: Placebo + Carvedilol
Placebo, Carvedilol
干预措施: Placebo (Drug)
Intervention Group: Apixaban + Carvedilol
Apixaban, Carvedilol
干预措施: Apixaban (Drug)
Control Group: Placebo + Carvedilol
Placebo, Carvedilol
干预措施: Carvedilol (Drug)
结局指标
主要结局
First Occurrence of Portal Hypertension-Related Complications
时间窗: 12 months
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.
次要结局
- Major and Minor Bleeding Events(12 months)
研究者
Mohammad sadik memon
Prof.Dr.
Asian Institute Of Medical Sciences