Hemodynamic Effect of the Combination of Simvastatin With Non-cardioselective Beta Blockers in Patients With Cirrhosis and Clinically Significant Portal Hypertension
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- improvement of the hemodynamic response rate
研究概览
简要总结
In the genesis and maintenance of PH associated with liver cirrhosis are two mechanisms that act synergistically. The first is an increase in hepatic vascular resistance, due in part to the disruption of liver structure inherent cirrhosis, and increased hepatic vascular tone is caused by the contraction of perivascular smooth muscle cells, myofibroblasts and hepatic stellate cells, which represents about 30% of global intrahepatic resistance and is believed to be due to the production Defective nitric oxide (NO). The second mechanism, which maintains and exacerbates HTP, is an increase of splanchnic blood flow caused by increased NO and other vasodilators at this level
In this regard, we believe that in patients with compensated liver cirrhosis, with portal pressure gradient> 10 mmHg, both acute responders betablockers test as non-responders, the association of antifibrotic drugs and / or vasodilators, chronic liver selective May be beneficial in the control of portal hypertension
详细描述
This study was prospective, randomized, controlled, double blind, in which patients who met the inclusion criteria and give written consent to participate in the study underwent a baseline hemodynamic study to determine the portal pressure gradient (GPSH). During the event, will assess the acute response to intravenous administration of propranolol. It is considered good hemodynamic response to declining GPSH >20% from baseline or decrease to <12 mmHg. At the conclusion of the baseline hemodynamic study patients will be divided into 2 treatment groups:
a) patients responding to treatment with beta-blockers, in which she was treated with nadolol at doses of 40mg/24horas (increasing the dose every 2-3 days as tolerated, to a maximum of 240 mg / 24 hours. Subsequently randomized into two treatment arms, double-blind:
a.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.
a.2: placebo capsules with external characteristics similar to simvastatin.
b) non-responders to treatment with beta blockers, carvedilol receive treatment with an initial dose of 6.25 mg / 24 hours, may increase to 25mg/dia if good clinical tolerance (HR and BP monitoring) and analytical (renal function and electrolyte disturbances) . Subsequently randomized into two treatment arms, double-blind b.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound,
- •PPG> 10 mmHg,
- •Presence of large esophageal varices or small varices with red spots, varices of any size and Pugh C, and / or gastric fundic varices of any size, in a recent gastroscopy (<1 month)
- •Absence of previous episodes of gastrointestinal bleeding
- •Written informed consent.
排除标准
- •Age <18 and> 80 years;
- •Episode of variceal bleeding,
- •Thrombosis splenoportal axis,
- •Hepatocarcinoma,
- •Terminal liver failure (Child-Pugh scale> 13 points);
- •Any comorbidity involving a medical drugs and / or a life expectancy <12 months,
- •Severe chronic renal insufficiency (creatinine> 150 g / L),
- •Absolute contraindication or allergy treatment with statins to simvastatin;
- •Concomitant potent inhibitors of CYP3A4 (eg., itraconazole, ketoconazole, inhibitors of HIV protease, erythromycin, clarithromycin, telithromycin and nefazodone),
- •Pretreatment (<1 month) or other lipid-lowering with simvastatin,
- •Previous episodes rhabdomyolysis;
- •Contraindication to beta-blockers (COPD with bronchial hyperresponsiveness, aortic stenosis, AV block, intermittent claudication, severe psychosis, bronchial asthma),
- •Hypersensitivity to beta blockers,
- •Concomitant administration of potent inhibitors of cytochrome P-450 (quinidine, fluoxetine, paroxetine, and propafenone)
- •Active alcoholic hepatitis,
- •Refusal to participate in the study or the informed consent claim;
- •Pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic shunts;
- •Pregnancy and lactation.
研究组 & 干预措施
simvasatin
a) patients responding to treatment with beta-blockers, in which she was treated with nadolol Subsequently randomized into two treatment arms, double-blind:
a.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.
a.2: placebo capsules with external characteristics similar to simvastatin.
b) non-responders to treatment with beta blockers, receive treatment with carvedilol.Subsequently randomized into two treatment arms, double-blind
b.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.
b.2: placebo capsules with external characteristics similar to simvastatin.
干预措施: Simvastatin (Drug)
placebo
干预措施: placebo (Drug)
结局指标
主要结局
improvement of the hemodynamic response rate
时间窗: 1 month.
The main objective is to assess whether, in patients with compensated cirrhosis, portal pressure greater than 10mmHg and esophageal varices at risk, the association of a liver selective vasodilator and simvastatin together with non-cardioselective beta blockers can improve the hemodynamic response rate.
次要结局
- Portal hypertension complications.(1 month)
- Adverse effects(1 month)