Propranolol, Carvedilol and Rosuvastatin in the Prevention of Recurrent Variceal Haemorrhage in Patients With Cirrhotic Portal Hypertension
试验速览
- 阶段
- 2 期
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Acute hemodynamic response
研究概览
简要总结
Patients with hepatic cirrhosis and previous variceal bleeding will be randomly assigned to use propranolol or carvedilol. After 8 weeks, rosuvastatin or placebo will be blindly added to nonresponders (HVPG measurement > 12mmHg) for another 8 weeks and hemodynamic response will be assessed again.
Surrogate serum markers of portal hypertension will be evaluated and correlated to HVPG values and to its variations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Hepatic cirrhosis of any etiology
- •Previous variceal bleeding
- •Endoscopic variceal eradication at least 2 weeks before
排除标准
- •Beta blocker or statin contraindications
- •Model for End-Stage Liver Disease (MELD) score > 25
- •Child-Pugh score > 13
- •HVPG ≤ 12 mmHg
- •Creatinine clearance < 50 mL/min
- •Refractory ascites
- •Hepatic encephalopathy stages 3 or 4
- •Alcohol use in the last 6 months
- •Hepatitis C treatment in the last 6 months
- •Changing or initiating a new hepatitis B treatment in the last 6 months
- •Malignant neoplasms from any origin except basal cell carcinoma
- •HIV infection
- •Pregnancy
- •Anticoagulation
- •Recent or complete portal vein thrombosis
研究组 & 干预措施
Phase 1: Propranolol (PPL)
Hepatic venous pressure gradient (HVPG) will be measured before and after 120 minutes of a loading dose of Propranolol (PPL) 80 mg PO. Thereafter, patients will receive maintenance therapy with Propranolol (40 to 320 mg / day) adjusted according to blood pressure and heart rate. After 28 days of reaching the maximum tolerated dose, a new HVPG measurement will be performed.
干预措施: Propranolol (Drug)
Phase 1: Carvedilol (CVD)
HVPG will be measured before and after 120 minutes of a loading dose of Carvedilol (CVD) 12.5 mg PO. Thereafter, patients will receive maintenance therapy with Carvedilol (6.25 - 25 mg / day) adjusted according to blood pressure. After 28 days of reaching the maximum tolerated dose, a new HVPG measurement will be performed.
干预措施: Carvedilol (Drug)
Phase 2: PPL non-responders/rosuvastatin
Patients treated with PROPRANOLOL (PPL) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of ROSUVASTATIN 20 mg /day PO. HVPG will be measured again after 56 days.
干预措施: Propranolol (Drug)
Phase 2: PPL non-responders/rosuvastatin
Patients treated with PROPRANOLOL (PPL) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of ROSUVASTATIN 20 mg /day PO. HVPG will be measured again after 56 days.
干预措施: Rosuvastatin (Drug)
Phase 2: PPL non-responders/placebo
Patients treated with PROPRANOLOL (PPL) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of PLACEBO 1 tablet PO. HVPG will be measured again after 56 days.
干预措施: Propranolol (Drug)
Phase 2: PPL non-responders/placebo
Patients treated with PROPRANOLOL (PPL) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of PLACEBO 1 tablet PO. HVPG will be measured again after 56 days.
干预措施: Placebo (Drug)
Phase 2: CVD non-responders/rosuvastatin
Patients treated with CARVEDILOL (CVD) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of ROSUVASTATIN 20 mg /day PO. HVPG will be measured again after 56 days.
干预措施: Carvedilol (Drug)
Phase 2: CVD non-responders/rosuvastatin
Patients treated with CARVEDILOL (CVD) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of ROSUVASTATIN 20 mg /day PO. HVPG will be measured again after 56 days.
干预措施: Rosuvastatin (Drug)
Phase 2: CVD non-responders/placebo
Patients treated with CARVEDILOL (CVD) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of PLACEBO 1 tablet PO. HVPG will be measured again after 56 days.
干预措施: Carvedilol (Drug)
Phase 2: CVD non-responders/placebo
Patients treated with CARVEDILOL (CVD) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of PLACEBO 1 tablet PO. HVPG will be measured again after 56 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Acute hemodynamic response
时间窗: Two hours after a load dose of carvedilol or propranolol
A decrease in HVPG to 12 mmHg or lower
Full hemodynamic response to beta blockers
时间窗: Eight weeks of carvedilol or propranolol
A decrease in HVPG to 12 mmHg or lower
Full hemodynamic response to beta blockers plus rosuvastatin or placebo
时间窗: Eight weeks of beta blockers plus rosuvastatin or placebo
A decrease in HVPG to 12 mmHg or lower
次要结局
- Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo(Eight weeks of beta blockers plus rosuvastatin or placebo)
- Partial hemodynamic response to beta blockers plus rosuvastatin or placebo(Eight weeks of beta blockers plus rosuvastatin or placebo)
研究者
Guilherme Rezende
Associated Professor
Universidade Federal do Rio de Janeiro