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

• ClinicalTrials.gov Identifier: NCT00693225
• Recruitment Status: Completed
• First Posted: June 6, 2008
• Results First Posted: September 20, 2012
• Last Update Posted: September 20, 2012
• Sponsor: Yvonne Romero
• Collaborator: Bausch Health Americas, Inc.
• Information provided by (Responsible Party): Yvonne Romero, Mayo Clinic

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Erosive Esophagitis
• Intervention: Drug: Omeprazole/sodium bicarbonate
• Enrollment: 91

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.

Arm/Group Title	Omeprazole/Sodium Bicarbonate AM Dose	Omeprazole/Sodium Bicarbonate PM Dose
Arm/Group Description	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime
Period Title: Overall Study
Started	43	48
Completed	41	43
Not Completed	2	5
Reason Not Completed
Lost to Follow-up	1	2
Adverse Event	1	3

Baseline Characteristics

Arm/Group Title		Omeprazole/Sodium Bicarbonate AM Dose	Omeprazole/Sodium Bicarbonate PM Dose	Total
Arm/Group Description		8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime	Total of all reporting groups
Overall Number of Baseline Participants		43	48	91
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	43 participants	48 participants	91 participants
		58; (19 to 86)	59; (30 to 86)	58; (19 to 86)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	43 participants	48 participants	91 participants
	Female	13 30.2%	15 31.3%	28 30.8%
	Male	30 69.8%	33 68.8%	63 69.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	43 participants	48 participants	91 participants
		43	48	91
Body Mass Index (BMI); Mean (Full Range); Unit of measure: Kg/m^2
	Number Analyzed	43 participants	48 participants	91 participants
		31.1; (24.5 to 51)	31.1; (21.2 to 46.8)	31.1; (21.2 to 51)
Esophagitis Severity [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants	48 participants	91 participants
LA grade C (moderate esophagitis)		26	33	59
LA grade D (severe esophagitis)		17	15	32
		[1] Measure Description: Esophagitis Severity was measured in Los Angeles (LA) Classification system, which quantifies erosive esophagitis and is graded on an A-D scale with increasing severity of injury.

Outcome Measures

1. Primary Outcome

Title	Percent of Subjects Overall Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omeprazole/Sodium Bicarbonate AM Dose	Omeprazole/Sodium Bicarbonate PM Dose
Arm/Group Description:	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime
Overall Number of Participants Analyzed	41	43
Measure Type: Number; Unit of Measure: percentage of patients
Healed	83	81
Improved	15	14
Same or worse	2	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omeprazole/Sodium Bicarbonate AM Dose, Omeprazole/Sodium Bicarbonate PM Dose
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1.0
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

2. Secondary Outcome

Title	Percent of Subjects With Moderate Esophagitis (LA Grade C) Who Healed, Improved, or Stayed the Same or Worsened After 8 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Omeprazole/Sodium Bicarbonate AM Dose	Omeprazole/Sodium Bicarbonate PM Dose
Arm/Group Description:	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime
Overall Number of Participants Analyzed	25	29
Measure Type: Number; Unit of Measure: percentage of participants
Healed	88	79
Improved	12	14
Same or worse	0	7

3. Secondary Outcome

Title	Percent of Subjects With Severe Esophagitis (LA Grade D) Who Healed, Improved, or Stayed the Same After 8 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Omeprazole/Sodium Bicarbonate AM Dose	Omeprazole/Sodium Bicarbonate PM Dose
Arm/Group Description:	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime
Overall Number of Participants Analyzed	16	14
Measure Type: Number; Unit of Measure: percentage of participants
Healed	75	86
Improved	19	14
Same	6	0

Adverse Events

Time Frame	Adverse events were collected over the eight weeks subjects were on study drug.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Omeprazole/Sodium Bicarbonate AM Dose		Omeprazole/Sodium Bicarbonate PM Dose
Arm/Group Description	8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken in the morning		8 weeks of therapy with omeprazole/sodium bicarbonate oral suspension 40 mg, once per day, taken at bedtime
All-Cause Mortality
	Omeprazole/Sodium Bicarbonate AM Dose		Omeprazole/Sodium Bicarbonate PM Dose
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Omeprazole/Sodium Bicarbonate AM Dose		Omeprazole/Sodium Bicarbonate PM Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0.00%)		0/43 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Omeprazole/Sodium Bicarbonate AM Dose		Omeprazole/Sodium Bicarbonate PM Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.44%)		3/43 (6.98%)
Blood and lymphatic system disorders
peripheral edema/increased blood pressue †	0/41 (0.00%)	0	3/43 (6.98%)	3
Musculoskeletal and connective tissue disorders
Joint and muscle pain †	1/41 (2.44%)	1	0/43 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

Our methods relied upon pill counting as a proxy for adherence to medical therapy. Now that PPIs are available over the counter, few patients present de novo with LA C and LA D esophagitis. We didn't control for other factors that can affect GERD.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Yvonne Romero
• Organization: Mayo Clinic
• Phone: 507-266-9156
• EMail: romero.yvonne@mayo.edu

• Responsible Party: Yvonne Romero, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00693225
• Other Study ID Numbers: 07-008503
• First Submitted: June 4, 2008
• First Posted: June 6, 2008
• Results First Submitted: August 21, 2012
• Results First Posted: September 20, 2012
• Last Update Posted: September 20, 2012