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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
435
Azithromycin, a semi-synthetic macrolide antibiotic derived from erythromycin. The role of azithromycin as a prokinetic agent was first reported in a retrospective cohort study, which showed azithromycin to be equivalent to erythromycin in accelerating gastric emptying in patients with gastroparesis. The aim of this intervention arm is to evaluate the effectiveness of azithromycin as a prokinetic agent in the management of UGIB.
Metoclopramide, a 5-HT4 agonist and a dopamine D2-receptor antagonist, is approved for short-term treatment of gastroparesis. The use of metoclopramide as a prokinetic agent in the setting of UGIB has been previously studied, but the number of subject involved was too low to adequately power the studies. The aim of this intervention arm is to further evaluate the effectiveness of metoclopramide as a prokinetic agent in the management of UGIB.
Normal saline is used as a placebo control.
Rhode Island Hospital
Providence, Rhode Island, United States
RECRUITINGRate of Reduction in the Need for Second Endoscopy
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.
Time frame: 48 hours
Adverse Cardiac Side Effects related to Intervention
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.
Time frame: 5 days
Adverse Infectious Disease Side Effects related to Intervention
The primary infectious disease outcome measure is the incidence of C. difficile infection, occurring within 30 days of azithromycin administration.
Time frame: 30 days
Adverse Neurological Side Effects related to Intervention
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.
Time frame: 48 hours
Quality of Endoscopic Visualization
Endoscopic visibility is graded using the standard 4-point objective scoring system as described in most endoscopy literature. The corpus, fundus, and duodenal bulb are scored separately based on an independent review of the images captured by the endoscopist. If a second endoscopy is performed within 48 hours of the initial endoscopy, the presence of clinically significant lesions not identified during the first endoscopy is also measured.
Time frame: 48 hours
All-Cause Mortality
All-Cause Mortality within 30 days.
Time frame: 30 days.
Number of Unit of Transfusion
Number of units of packed red blood cells transfused before hemostasis has been achieved or death.
Time frame: 30 days
Length of Hospital Stay
Length of hospital stay since admission for current episode of GIB.
Time frame: 30 days
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