Clinical trial NCT03840057: Metoclopramide, Azithromycin, or Nondrug Pretreatment for UGIB to Reduce Second Endoscopy
Official title: Metoclopramide, Azithromycin, or Nondrug Pretreatment for Upper Gastrointestinal Bleeding to Reduce Second Endoscopy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastro Intestinal Bleeding
Upper Gastrointestinal Bleeding
Keywords: GIB
UGIB
Lead sponsor: Lifespan
Sponsor class: OTHER
First posted: 2019-02-15
Enrollment: 435
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study is comprised of two intervention arms, namely the azithromycin arm and the metoclopramide arm, as well as one placebo arm. The two interventions would be studied sequentially in order to simplify the logistical challenges of the blinding and placebo-control processes. The current study is comprised to two parts. During Part 1 of the study, participants are randomized to either azithromycin 500mg intravenous infusion or equivalent volume of 0.9% sodium chloride infusion in a 2-to-1 ratio. During Part 2 of the study, participants are randomized to either metoclopramide 10mg intravenous injection or equivalent volume of 0.9% sodium chloride injection in a 2-to-1 ratio. The 0.9% sodium chloride arm from the two parts of the study are pooled together to form the placebo arm during final analysis.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Rate of Reduction in the Need for Second Endoscopy
timeFrame: 48 hours
measure: Adverse Cardiac Side Effects related to Intervention
timeFrame: 5 days
measure: Adverse Infectious Disease Side Effects related to Intervention
timeFrame: 30 days
measure: Adverse Neurological Side Effects related to Intervention
timeFrame: 48 hours
Secondary outcomes:
measure: Quality of Endoscopic Visualization
timeFrame: 48 hours
measure: All-Cause Mortality
timeFrame: 30 days.
measure: Number of Unit of Transfusion
timeFrame: 30 days
measure: Length of Hospital Stay
timeFrame: 30 days
Other outcomes:
Locations:
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.