Metoclopramide, Azithromycin, or Nondrug Pretreatment for UGIB to Reduce Second Endoscopy

Phase 2

• Conditions: Gastro Intestinal Bleeding; Upper Gastrointestinal Bleeding
• Interventions: Drug: Sodium chloride 0.9%; Drug: Azithromycin Injection; Drug: Metoclopramide Injectable Solution

• Registration Number: NCT03840057
• Lead Sponsor: Waihong Chung

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-02-07
• Study First Submitted QC: 2019-02-11
• Study First Posted: 2019-02-15
• Study Start: 2020-07-01
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-05
• Last Update Posted: 2020-08-07
• Primary Completion: 2021-06
• Study Completion: 2021-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 435

Inclusion Criteria

• 1. Adult patients ≥ 18 years of age at the time of presentation;
• 2. Admitted to Rhode Island Hospital (RIH) emergency room or inpatient services;
• 3. Presented with hematemesis, coffee ground emesis, or melena;
• 4. Upper endoscopy is planned within 24 hours of presentation or onset of bleeding.

Exclusion Criteria

• 1. Known anaphylactic allergic reaction to erythromycin, azithromycin, and/or metoclopramide;
• 2. 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;
• 3. 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;
• 4. Known history of TD, ventricular arrhythmias , or long QT syndrome;
• 5. Already received erythromycin and/or azithromycin within the past 10 days, or metoclopramide within the past 4 days for other indications;
• 6. Recipient of hematopoietic stem cell transplant;
• 7. History of Neisseria gonorrhoeae infection;
• 8. Pregnancy;
• 9. Prior gastrectomy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Sodium chloride 0.9%	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.
Azithromycin	Azithromycin Injection	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.
Metoclopramide	Metoclopramide Injectable Solution	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.

Primary Outcome Measures

Name	Time	Method
Rate of Reduction in the Need for Second Endoscopy	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	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	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	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.

Secondary Outcome Measures

Name	Time	Method
All-Cause Mortality	30 days.	All-Cause Mortality within 30 days.
Quality of Endoscopic Visualization	48 hours	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.
Number of Unit of Transfusion	30 days	Number of units of packed red blood cells transfused before hemostasis has been achieved or death.
Length of Hospital Stay	30 days	Length of hospital stay since admission for current episode of GIB.

Trial Locations

Locations (1)

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States