- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03840057
Metoclopramide, Azithromycin, or Nondrug Pretreatment for UGIB to Reduce Second Endoscopy (MANPURSE)
August 5, 2020 updated by: Waihong Chung
Metoclopramide, Azithromycin, or Nondrug Pretreatment for Upper Gastrointestinal Bleeding to Reduce Second Endoscopy
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 Overview
Status
Unknown
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
435
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Waihong Chung, MD PhD
- Phone Number: 401-444-5280
- Email: waihong.chung@lifespan.org
Study Locations
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02906
- Recruiting
- Rhode Island Hospital
-
Contact:
- Waihong Chung, MD, PhD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
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.
|
Experimental: 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.
|
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 Comparator: 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.
|
Normal saline is used as a placebo control.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Reduction in the Need for Second Endoscopy
Time Frame: 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.
|
48 hours
|
Adverse Cardiac Side Effects related to Intervention
Time Frame: 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.
|
5 days
|
Adverse Infectious Disease Side Effects related to Intervention
Time Frame: 30 days
|
The primary infectious disease outcome measure is the incidence of C. difficile infection, occurring within 30 days of azithromycin administration.
|
30 days
|
Adverse Neurological Side Effects related to Intervention
Time Frame: 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.
|
48 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Endoscopic Visualization
Time Frame: 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.
|
48 hours
|
All-Cause Mortality
Time Frame: 30 days.
|
All-Cause Mortality within 30 days.
|
30 days.
|
Number of Unit of Transfusion
Time Frame: 30 days
|
Number of units of packed red blood cells transfused before hemostasis has been achieved or death.
|
30 days
|
Length of Hospital Stay
Time Frame: 30 days
|
Length of hospital stay since admission for current episode of GIB.
|
30 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012 Mar;107(3):345-60; quiz 361. doi: 10.1038/ajg.2011.480. Epub 2012 Feb 7.
- Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, Rotondano G, Hucl T, Dinis-Ribeiro M, Marmo R, Racz I, Arezzo A, Hoffmann RT, Lesur G, de Franchis R, Aabakken L, Veitch A, Radaelli F, Salgueiro P, Cardoso R, Maia L, Zullo A, Cipolletta L, Hassan C. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015 Oct;47(10):a1-46. doi: 10.1055/s-0034-1393172. Epub 2015 Sep 29.
- Lee A, Kuo B. Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. doi: 10.1586/eem.10.41.
- Larson JM, Tavakkoli A, Drane WE, Toskes PP, Moshiree B. Advantages of azithromycin over erythromycin in improving the gastric emptying half-time in adult patients with gastroparesis. J Neurogastroenterol Motil. 2010 Oct;16(4):407-13. doi: 10.5056/jnm.2010.16.4.407. Epub 2010 Oct 30.
- Moshiree B, McDonald R, Hou W, Toskes PP. Comparison of the effect of azithromycin versus erythromycin on antroduodenal pressure profiles of patients with chronic functional gastrointestinal pain and gastroparesis. Dig Dis Sci. 2010 Mar;55(3):675-83. doi: 10.1007/s10620-009-1038-3.
- Chini P, Toskes PP, Waseem S, Hou W, McDonald R, Moshiree B. Effect of azithromycin on small bowel motility in patients with gastrointestinal dysmotility. Scand J Gastroenterol. 2012 Apr;47(4):422-7. doi: 10.3109/00365521.2012.654402. Epub 2012 Feb 27.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 1, 2020
Primary Completion (Anticipated)
June 1, 2021
Study Completion (Anticipated)
July 1, 2021
Study Registration Dates
First Submitted
February 7, 2019
First Submitted That Met QC Criteria
February 11, 2019
First Posted (Actual)
February 15, 2019
Study Record Updates
Last Update Posted (Actual)
August 7, 2020
Last Update Submitted That Met QC Criteria
August 5, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Gastrointestinal Diseases
- Hemorrhage
- Gastrointestinal Hemorrhage
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Anti-Bacterial Agents
- Dopamine Agents
- Dopamine D2 Receptor Antagonists
- Dopamine Antagonists
- Azithromycin
- Metoclopramide
Other Study ID Numbers
- 1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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