Erosive Esophagitis
Conditions
Keywords
Erosive Esophagitis, Reflux Esophagitis, Gastroesophageal reflux disease, GERD, proton pump inhibitor, omeprazole/sodium bicarbonate
Brief 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.
Detailed 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.
Interventions
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.
Sponsors
Bausch Health Americas, Inc.
Yvonne Romero
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | 8 weeks | 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. |
| Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | 8 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Mayo Clinic in Rochester, MN from June 20, 2008 to May 24, 2010.
Pre-assignment details
One subject on the PM dose arm did not receive allocated intervention because the subject changed their mind soon after randomization.
Participants by arm
| Arm | Count |
|---|---|
| Omeprazole/Sodium Bicarbonate AM Dose 8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning | 43 |
| Omeprazole/Sodium Bicarbonate PM Dose 8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime | 48 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Omeprazole/Sodium Bicarbonate AM Dose | Omeprazole/Sodium Bicarbonate PM Dose | Total |
|---|---|---|---|
| Age Continuous | 58 years | 59 years | 58 years |
| Body Mass Index (BMI) | 31.1 kg/m^2 | 31.1 kg/m^2 | 31.1 kg/m^2 |
| Esophagitis Severity LA grade C (moderate esophagitis) | 26 participants | 33 participants | 59 participants |
| Esophagitis Severity LA grade D (severe esophagitis) | 17 participants | 15 participants | 32 participants |
| Region of Enrollment United States | 43 participants | 48 participants | 91 participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28 Participants |
| Sex: Female, Male Male | 30 Participants | 33 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 41 | 3 / 43 |
| serious Total, serious adverse events | 0 / 41 | 0 / 43 |
Outcome results
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.
Time frame: 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Healed | 83 percentage of patients |
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Improved | 15 percentage of patients |
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Same or worse | 2 percentage of patients |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Healed | 81 percentage of patients |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Improved | 14 percentage of patients |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Same or worse | 5 percentage of patients |
p-value: 1Fisher Exact
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.
Time frame: 8 weeks
Population: 25 of the 41 participants in the Omeprazole/sodium bicarbonate AM dose arm were LA Grade C. 29 of the 43 participants in the Omeprazole/sodium bicarbonate AM dose arm were LA Grade C.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Healed | 88 percentage of participants |
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Improved | 12 percentage of participants |
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Same or worse | 0 percentage of participants |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Healed | 79 percentage of participants |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Improved | 14 percentage of participants |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment | Same or worse | 7 percentage of participants |
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.
Time frame: 8 weeks
Population: 16 of the 41 participants in the Omeprazole/sodium bicarbonate AM dose arm were LA Grade D. 14 of the 43 participants in the Omeprazole/sodium bicarbonate PM dose arm were LA Grade D.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | Healed | 75 percentage of participants |
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | Improved | 19 percentage of participants |
| Omeprazole/Sodium Bicarbonate AM Dose | Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | Same | 6 percentage of participants |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | Healed | 86 percentage of participants |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | Improved | 14 percentage of participants |
| Omeprazole/Sodium Bicarbonate PM Dose | Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment | Same | 0 percentage of participants |