Impact of Timing on the Efficacy of Zegerid 40 mg in Healing Reflux Esophagitis: A Pilot Study

Erosive Esophagitis Clinical Trial

Official title:

Impact of Timing on the Efficacy of Omeprazole/Sodium Bicarbonate Zegerid 40 mg in Healing Reflux Esophagitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00693225
• Other study ID #: 07-008503
• Status: Completed
• Phase: Phase 4
• First received: June 4, 2008
• Last updated: August 21, 2012
• Start date: January 2008
• Est. completion date: December 2010

Study information

• Verified date: August 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to determine the effect of morning versus bedtime administration of omeprazole/sodium bicarbonate (Zegerid) on endoscopic healing for patients with moderate or severe reflux esophagitis. Our hypothesis was that bedtime administration of Zegerid would be superior in healing esophagitis compared to morning administration prior to a meal.

Description:

Hypothesis: The timing of administration of omeprazole/sodium bicarbonate (Zegerid) will impact nocturnal esophageal acid exposure and healing of esophagitis. Specifically, we hypothesize that omeprazole/sodium bicarbonate, taken at bedtime, will be superior in healing esophagitis compared to omeprazole/sodium bicarbonate taken in the morning.

Specific Aim: Compare the percent of subjects with moderate/severe esophagitis who achieve complete endoscopic resolution after 8 weeks of treatment (morning vs. bedtime).

Intervention: All subjects received a one-on-one educational session describing the normal physiology of the upper gastrointestinal tract, the pathophysiology of hiatal hernia and reflux esophagitis, and food stuffs that contribute to reflux, prior to their invitation to participate in the trial. Outpatients who underwent a clinically indicated esophagogastroduodenoscopy (EGD) as advised by their primary health care provider in an open-access endoscopy unit who were diagnosed with Los Angeles grade C or D erosive reflux esophagitis were invited to participate.

Omeprazole/sodium bicarbonate powder for oral suspension 40 mg was supplied in individual packets that are emptied into a small cup containing 15-30 ml (1-2 tablespoons) of water, one per day, for 8 weeks. They were asked to stir well and drink immediately then refill the cup with water and drink. Subjects assigned to morning dosing were instructed to take the medication on an empty stomach, immediately upon rising, 20 to 60 minutes prior to chewing a solid. Subjects assigned to bedtime dosing were instructed to keep the medication by their bedside; taking the medication in a standing or seated upright position immediately before turning off the lights with the intention to sleep. The subject was instructed to not use other liquids or foods for 20 minutes after taking their study medication for those allocated to morning dosing, and until the next morning for those allocated to bedtime dosing.

Gelusil™ was distributed for use as an "on demand" rescue antacid; the frequency of use was recorded with the plan to use Gelusil™ consumption as a potential confounder of omeprazole/sodium bicarbonate efficacy. Other antacids, including sodium bicarbonate, magnesium hydroxide, calcium carbonate, and sucralfate were prohibited. Subjects taking non-omeprazole proton pump inhibitors (PPIs) and/or Histamine Receptor Antagonist (HRAs) were advised to discontinue these medications while they participated in this study. No other medication was altered for this study.

After 8 weeks, a follow-up EGD was performed to assess mucosal integrity by an endoscopist blinded to the study and subject allocation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects who have either moderate to severe erosive esophagitis (Los Angeles grade C or D)

2. Subjects with esophagitis despite use of a non-omeprazole Proton Pump Inhibitor (PPI)(s) or histamine receptor antagonist (HRA) were invited to participate without a wash-out period.

3. Subjects able to return to Mayo Clinic Rochester for follow up endoscopy 8 weeks after start of study.

4. Female subjects are eligible if they are not pregnant or lactating and one of the following criteria is met:

1. Surgically sterile (by means of hysterectomy or bilateral tubal ligation).

2. At least one year postmenopausal (no menses for greater than or equal to 12 months).

3. Subject is using a highly effective method of contraception, if of childbearing potential and has a negative urine human chorionic gonadotropin beta subunit (B-HCG) pregnancy test during screening, and prior to trial drug administration.

Exclusion Criteria:

1. Subjects already on or failed omeprazole in past, or intolerant of PPI therapy

2. Subjects who are using clopidogrel (Plavix)

3. Subjects with one or more of the following diagnoses:

1. Neoplasm of the esophagus or stomach

2. Previous upper gastrointestinal surgery (esophagectomy, Heller myotomy, hiatal hernial repair)

3. Diabetic gastroparesis

4. Esophageal motility disorder: Achalasia or scleroderma

5. Zollinger-Ellison syndrome

6. Infection with human immunodeficiency virus (HIV)

7. Bleeding diathesis

8. History of gastric or small bowel obstruction

9. Inability to read due to blindness, cognitive dysfunction, English language illiteracy

10. Disorders which predispose to unreliable responses such as Schizophrenia, Alzheimer's disease or significant memory loss

11. Pregnant and lactating females will be excluded as PPIs are not thought safe for the fetus (Pregnancy Category C).

4. Children younger than 18 years of age will be excluded as their compliance might be dictated by others, such as their parents, and their results would not be generalizable to the adult population. Other vulnerable populations, such as those with diminished mental acuity, will be excluded for the same reason.

5. Residence outside of the US (due to difficulties with overseas postal service) or in prison.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Erosive Esophagitis
• Esophagitis
• Esophagitis, Peptic

Intervention

Drug:
• Omeprazole/sodium bicarbonate
Omeprazole/sodium bicarbonate powder for oral suspension 40 mg was supplied in individual packets that were emptied into a small cup containing 15-30 ml (1-2 tablespoons) of water, one per day, for 8 weeks.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Yvonne Romero	Valeant Pharmaceuticals International, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment	After 8 weeks of treatment a follow-up esophagogastroduodenoscopy (EGD) was performed by an endoscopist blinded to the study and subject allocation. The evaluation results were grouped as follows: LA C esophagitis at baseline: healed = no erosions in the esophagus; improved= LA grades A or B; Same or worse = C or D at follow-up LA D esophagitis at baseline: healed = no erosions in the esophagus; improved=LA grades A, B, or C; Same=LA grade D at follow-up.	8 weeks	No
Secondary	Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment	After 8 weeks of treatment a follow-up esophagogastroduodenoscopy (EGD) was performed by an endoscopist blinded to the study and subject allocation. The evaluation results were grouped as follows: LA C esophagitis at baseline: healed = no erosions in the esophagus; improved= LA grades A or B; Same or worse = C or D at follow-up LA D esophagitis at baseline: healed = no erosions in the esophagus; improved=LA grades A, B, or C; Same=LA grade D at follow-up.	8 weeks	No
Secondary	Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment	After 8 weeks of treatment a follow-up esophagogastroduodenoscopy (EGD) was performed by an endoscopist blinded to the study and subject allocation. The evaluation results were grouped as follows: LA C esophagitis at baseline: healed = no erosions in the esophagus; improved= LA grades A or B; Same or worse = C or D at follow-up LA D esophagitis at baseline: healed = no erosions in the esophagus; improved=LA grades A, B, or C; Same=LA grade D at follow-up.	8 weeks	No