Carvedilol plus endoscopic variceal ligation versus propranolol plus endoscopic ligation for secondary prophylaxis of variceal bleed in cirrhosis: an open label randomized controlled trial
试验速览
- 阶段
- 2/3 期
- 状态
- 尚未招募
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Time to first variceal re-bleed
研究概览
简要总结
Non-selective beta blockers (NSBB) are the mainstay of pharmacological prophylaxis of variceal bleed in cirrhosis. While endoscopic variceal ligation (EVL) or NSBB alone is recommended for decreasing the risk of first variceal bleed (primary prophylaxis), prevention of variceal re-bleed (secondary prophylaxis) requires the combination of EVL and NSBB therapy.
Nadolol, propranolol and Carvedilol are the commonly used NSBB for variceal bleed prophylaxis. Unlike Nadolol and propranolol, Carvedilol has additional alpha-1 antagonistic action with consequent higher reductions in intrahepatic vascular resistance and hepatic venous pressure gradient (HVPG). The role of Carvedilol in primary prophylaxis of variceal hemorrhage is well established. Overall, Carvedilol appears to be superior to propranolol in reducing HVPG and is at par with EVL or propranolol in preventing first episode of variceal bleeding.
However, the role of Carvedilol in secondary prophylaxis of variceal hemorrhage remains a grey zone. Carvedilol causes a significantly higher reduction in MAP in comparison to propranolol which can be particularly problematic in patients with ascites who already have compromised systemic hemodynamics. There have also been concerns regarding hyponatremia, increased diuretic requirement and orthostatic hypotension with use of carvedilol. The paucity of available data of carvedilol use for secondary prophylaxis and concerns over its systemic effects is reflected in the fact that none of the expert societies recommend carvedilol as a superior agent to propranolol for secondary prophylaxis. In a recent retrospective non randomized study from Europe Carvedilol appeared to be superior to propranolol in decreasing HVPG, re-bleed and liver related deaths without significant worsening of renal dysfunction. There is no published RCT or prospective study on clinical outcomes with the use of Carvedilol and EVL vis-a-vis propranolol and EVL for preventing variceal re-bleed (secondary prophylaxis), in patients with cirrhosis. This study is thus being planned to study the role of Carvedilol in conjunction with EVL versus propranolol with EVL as secondary prophylaxis in patients presenting with index variceal bleed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Cirrhosis (of any etiology) as diagnosed on the basis of blood parameters, imaging or Fibro Scan
- •Source of UGIB is determined to be from esophageal varices and is successfully tackled using EVL.
- •Variceal origin of UGIB will be considered based on endoscopic findings of: a.
- •Ongoing bleed from esophageal varices b.
- •Endoscopic stigmata of recent or high risk of bleed including red coloured streaks, blue hemocystic spot, cherry red sign and nipple sign c.
- •No other source of bleed and presence of bandable varices
- •Patients with acute kidney injury (International Ascites Club criteria) or acute- on-chronic liver failure (as per the CANONIC definition) at presentation will be included in the study only if these have resolved by the time of randomization.
排除标准
- •Patients who are already receiving NSBB at index presentation
- •Failure to control UGIB using EVL
- •Presence of gastric varices
- •Presence of hepatocellular carcinoma or other active malignancy
- •Presence of portal vein thrombosis
- •Patients with acute-on-chronic liver failure (as per the CANONIC definition) at the time of randomization
- •Patients with bradycardia, sick-sinus syndrome, heart-block or other significant ECG abnormalities
- •Systolic blood pressure less than 90 mm-Hg or mean arterial pressure less than 70 mm-Hg at the time of randomization
- •Patients with bronchial asthma, chronic obstructive airway disease, peripheral vascular disease, Raynauds phenomenon or other contraindications to the use of non selective beta blockers.
- •Patients with transjugular intrahepatic portosystemic shunt (TIPS)
- •Patients having Refractory Ascites
- •Pregnant patients
- •Refusal to give informed consent.
结局指标
主要结局
Time to first variceal re-bleed
时间窗: within 12 months
次要结局
- Adverse events(within 12 months)
- - Early variceal re-bleed within 6-weeks of index EVL (bleed from post-EVL ulceration will not be considered as variceal re-bleed)(within 12 months)
- 12-month transplant free survival(within 12 months)
- Change in mean arterial pressure (MAP)(at 1month, 6 months and 12 months)
- Change in severity of portal hypertensive gastropathy (PHG). PHG will be graded as mild or severe depending on the absence or presence of central red spot.
- New onset acute kidney injury (AKI)(within 12-months)
- New onset Hepatic Encephalopathy(within 12 months)
- New onset Spontaneous Bacterial Peritonitis, other infections(within 12 months)
- Ascites control(at 6 and 12-months)
研究者
Arka De
Postgraduate Institute of Medical Education and Research