Metoclopramide, Azithromycin, or Nondrug Pretreatment for Upper Gastrointestinal Bleeding to Reduce Second Endoscopy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 435
- 试验地点
- 1
- 主要终点
- Rate of Reduction in the Need for Second Endoscopy
研究概览
简要总结
Early endoscopy is an integral part of the management plan for patients presenting with clinical signs of severe or ongoing UGIB. An accurate endoscopic diagnosis and successful endoscopic hemostasis is highly dependent on adequate visualization of the entire gastric mucosa. Metoclopramide has previously been investigated as a prokinetic agent to aid gastric emptying prior to endoscopy, but its widespread adoption is limited by a lack of high quality clinical evidence as well as concerns regarding side effects. Erythromycin is currently the only prokinetic agent recommended by the American and the European guidelines for use in selected patients in order to reduce the need for second endoscopy. Its clinical application, however, is limited by risk of arrhythmia, significant drug interactions, and frequent drug shortages. Azithromycin is structurally related to erythromycin, but is devoid of most adverse side effects associated with erythromycin use. Early evidence suggests that azithromycin may be an effective alternative to erythromycin in the treatment of gastroparesis. The current study, an interventional, randomized, triple-blinded, placebo-controlled clinical trial, is primarily aimed to evaluate the effectiveness of azithromycin as a prokinetic agent in the management of UGIB. It is also aimed to further evaluate the role of metoclopramide as a prokinetic agent in this setting. Outcome measures to be collected in this study include the need for secondary endoscopy, overall mortality, transfusion requirement, length of stay, requirement for surgery, and incidence of adverse side effects. Results from this study would help identify a safe, effective, and readily available prokinetic agent to be used prior to endoscopy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Initial management of UGIB would be performed by the primary team without interference from the investigator. If a gastroenterology consult were placed by the primary team, the endoscopist on-call would evaluate the patient per routine care. If an early endoscopy is deemed appropriate and necessary based on the patient's clinical status, the participant is registered to a central electronic database, which would assign participants to the intervention arm or the placebo arm using a permuted block randomization process. The appropriate medication or placebo is prepared and distributed by the central inpatient pharmacy. The investigator, the endoscopist, the study participant, and the primary team are all blinded to the assignment.
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
- •Adult patients ≥ 18 years of age at the time of presentation;
- •Admitted to Rhode Island Hospital (RIH) emergency room or inpatient services;
- •Presented with hematemesis, coffee ground emesis, or melena;
- •Upper endoscopy is planned within 24 hours of presentation or onset of bleeding.
排除标准
- •Known anaphylactic allergic reaction to erythromycin, azithromycin, and/or metoclopramide;
- •Concurrent use of certain medications associated with tardive dyskinesia (TD):
- •a. Fluphenazine,
- •b. Haloperidol,
- •c. Loxapine,
- •d. Paliperidone,
- •e. Perphenazine,
- •f. Pimozide,
- •g. Risperidone,
- •h. Thiothixene,
- •i. Trifluoperazine;
- •Concurrent use of certain medications associated with torsade de pointes:
- •a. Amiodarone,
- •b. Chlorpromazine,
- •c. Disopyramide,
- •d. Dofetilide,
- •e. Methadone,
- •f. Procainamide,
- •g. Quinidine,
- •h. Sotalol;
- •Known history of TD, ventricular arrhythmias , or long QT syndrome;
- •Already received erythromycin and/or azithromycin within the past 10 days, or metoclopramide within the past 4 days for other indications;
- •Recipient of hematopoietic stem cell transplant;
- •History of Neisseria gonorrhoeae infection;
- •Prior gastrectomy.
研究组 & 干预措施
Azithromycin
Participants randomized to the azithromycin arm would receive 250mL of reconstituted solution containing 500mg of generic azithromycin to be administered as a slow intravenous infusion over 1 hour by the primary team 30-120 minutes prior to endoscopy. No dosage adjustment is made for those with hepatic or renal impairment. No dose adjustment is made for geriatric population.
干预措施: Azithromycin Injection (Drug)
Metoclopramide
Participants randomized to the metoclopramide arm would receive 2mL of solution containing 10mg of generic metoclopramide to be administered as a direct intravenous push by the primary team 5-60 minutes prior to endoscopy. No dosage adjustment is made for those with hepatic impairment. A 50% dose reduction is made for those with creatinine clearance of less than 40mL/minute. No dose adjustment is made for geriatric population.
干预措施: Metoclopramide Injectable Solution (Drug)
Placebo
Participants randomized to the placebo arm during Part 1 (azithromycin) of the study would receive 250mL of 0.9% sodium chloride solution to be administered as a slow intravenous infusion over 1 hour by the primary team 30-120 minutes prior to endoscopy. Participants randomized to the placebo arm during Part 2 (metoclopramide) of the current study would receive 2mL of 0.9% sodium chloride solution to be administered as a direct intravenous push by the primary team 5-60 minutes prior to endoscopy.
干预措施: Sodium chloride 0.9% (Drug)
结局指标
主要结局
Rate of Reduction in the Need for Second Endoscopy
时间窗: 48 hours
The primary outcome measure of effectiveness is a reduction in the need for second endoscopy within 48 hours of the first endoscopy. This primary outcome measure is chosen because it represents the basis of current American and European guideline recommendations regarding erythromycin.
Adverse Cardiac Side Effects related to Intervention
时间窗: 5 days
The primary cardiac outcome measure is the incidence of unstable arrhythmia, occurring within 5 days of azithromycin administration, requiring cardioversion or resulting in cardiac arrest.
Adverse Infectious Disease Side Effects related to Intervention
时间窗: 30 days
The primary infectious disease outcome measure is the incidence of C. difficile infection, occurring within 30 days of azithromycin administration.
Adverse Neurological Side Effects related to Intervention
时间窗: 48 hours
The primary neurological outcome measure is the incidence of any reversible or irreversible extrapyramidal symptom, such as acute dystonic reactions, akathisia, drug-induced Parkinsonism, and tardive dyskinesia, within 48 hours of metoclopramide administration.
次要结局
- All-Cause Mortality(30 days.)
- Quality of Endoscopic Visualization(48 hours)
- Number of Unit of Transfusion(30 days)
- Length of Hospital Stay(30 days)
研究者
Waihong Chung
Fellow
Lifespan