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

NCT ID: NCT03840057

Last Updated: 2020-08-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 435 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2021-07-31

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.

Conditions

Gastro Intestinal Bleeding; Upper Gastrointestinal Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Azithromycin Injection

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Metoclopramide Injectable Solution

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Sodium chloride 0.9%

Intervention Type: DRUG

Normal saline is used as a placebo control.

Interventions

Azithromycin Injection

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.

Intervention Type: DRUG

Metoclopramide Injectable Solution

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.

Intervention Type: DRUG

Sodium chloride 0.9%

Normal saline is used as a placebo control.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Waihong Chung

OTHER

Sponsor Role: lead

Responsible Party

Waihong Chung

Fellow

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Waihong Chung, MD PhD

Role: CONTACT

waihong.chung@lifespan.org

401-444-5280

Facility Contacts

Waihong Chung, MD, PhD

Role: primary

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

1

Identifier Type: -

Identifier Source: org_study_id