Phase 3 Study of Effect of Intravenous and Oral Esomeprazole in Prevention of Recurrent Bleeding From Peptic Ulcers After Endoscopic Therapy (IOE Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 263
- 试验地点
- 2
- 主要终点
- Rate of clinical rebleeding within 30 day of endoscopic therapy
研究概览
简要总结
The investigators previously showed that the use of a high-dose intravenous PPI regimen after endoscopic control of bleeding from peptic ulcers reduced rate of recurrent bleeding, decreased the need for endoscopic and surgical interventions and in general improved patients' outcomes. A trend towards reduced mortality associated with the use of high-dose intravenous PPI was also observed. Recent clinical trials from Asia have provided evidence that high-dose oral PPIs are associated with a reduction in rebleeding. Current meta-analysis suggests that both high dose (intravenous) and low dose (oral) PPIs effectively reduce rebleeding vs placebo. However, there has been no clinical study to compare IV infusion to oral PPI in this patient population.
The purpose of this clinical study is to compare the efficacy and safety of intravenous and oral Esomeprazole in patients with peptic ulcer hemorrhage who are at risk for recurrent bleeding. The investigators hypothesize that using IV infusion is superior to oral PPI.
详细描述
The investigators previously showed that the use of a high-dose intravenous PPI regimen after endoscopic control of bleeding from peptic ulcers reduced rate of recurrent bleeding, decreased the need for endoscopic and surgical interventions and in general improved patients' outcomes. A trend towards reduced mortality associated with the use of high-dose intravenous PPI was also observed. Recent clinical trials from Asia have provided evidence that high-dose oral PPIs are associated with a reduction in rebleeding. Current meta-analysis suggests that both high dose (intravenous) and low dose (oral) PPIs effectively reduce rebleeding vs placebo. However, there has been no clinical study to compare IV infusion to oral PPI in this patient population.
Endoscopic stigmata in bleeding peptic ulcers are prognostic and allow risk stratification. Patients with a clean ulcer base have a < 5% risk of rebleeding; this increases progressively with a flat spot, adherent clot, non-bleeding visible vessel and active bleeding (55%). Early endoscopy in patients with bleeding peptic ulcers selects the high risk ulcers for therapy and evaluation of adjuvant PPI use.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Confirmed ulcer bleeding with Forrest Ia, Ib, IIa, IIb
- •Endoscopic hemostasis achieved
- •Informed consent obtained
排除标准
- •No consent
- •Forrest II c, III (clear ulcer base/flat spot and no active bleeding, i.e., minimal risk for rebleeding)
- •Unsuccessful endoscopic treatment (i.e., injection and/or thermal coagulation for the initial bleeding) or severe bleeding that immediate surgery is indicated
- •Moribund patients in whom active treatment of any form is not considered.
- •Polytrauma, severe injury, unconsciousness, burns, or need for continuous artificial ventilation
- •Upper GI malignancy or disseminated malignant disease
- •Esophageal varices
- •A Mallory-Weiss lesion
- •Phenytoin or theophylline treatment
- •Uses of PPI or H2RAs within 3 days of admission, including uses at Emergency Department N.B. Usage of aspirin or NSAID is not an exclusion criteria.
研究组 & 干预措施
oral esomeprazole
- Esomeprazole placebo IV loading bolus
- Esomeprazole placebo intravenous infusion for 72 hours
- Oral Esomeprazole: 80 mg/Day on Day 1, 2 and Day 3, and the drug will be given as 40 mg q12h.
干预措施: Oral esomeprazole (Drug)
Intravenous Esomeprazole
Esomeprazole IV loading bolus 80mg
• Esomeprazole intravenous infusion 8mg/hr for 72 hours
干预措施: Intravenous Esomeprazole (Drug)
结局指标
主要结局
Rate of clinical rebleeding within 30 day of endoscopic therapy
时间窗: 30 days
Definition of clinical rebleeding 1. Recurrent hematemesis 2. fresh melena after normal stool 3. Hypotension SBP\<90 or tachycardia \>110 AND fresh melena 4. Decrease in Hb \>2g/dL (or Hct \> 10%) during any 24 h or an increas in Hb \<1 g/dL (or Hct \<3%) despite ≥4 units of blood has been transfused during any 48h
次要结局
- Un-scheduled further endoscopic therapy(30 days)
- Duration of hospitalization(30 days)
- un-scheduled further endoscopic therapy(30 days)
- Need for surgery(30 days)
- Blood transfusion(30 days)
- mortality(30 days)
- need of surgery(30 days)
研究者
Francis KL Chan
professor
Chinese University of Hong Kong