Trial Outcomes & Findings for The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis (NCT NCT00728481)

NCT ID: NCT00728481

Last Updated: 2016-01-14

Results Overview

Subjects with Esophageal eosinophilia experiencing a histological response to treatment. Subjects were considered to have histological response to treatment if both sets of biopsies (from the distal and mid-esophagus) had, on average, less than 5 eosinophils per high power field (eos/hpf) at the 6-month biopsies.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

51 participants

Primary outcome timeframe

Baseline, 6 months

Results posted on

2016-01-14

Participant Flow

Subjects with a clinical diagnosis of Eosinophilic Esophagitis (EE) were recruited by mail using a Mayo Clinic proprietary database and also by direct contact in the Mayo Clinic Esophageal Diseases speciality clinic in Rochester, MN. Subjects were enrolled from 3/2009 to 8/2010.

Patients with esophageal eosinophilic infiltration of greater than or equal to 15 eos/hpf as determined by 4 biopsies of the esophagus, then underwent a 24-hour transnasal catheter-based ambulatory pH study to determine amount of distal esophageal acid exposure, and were placed in one of 2 treatment arms based on positive or negative pH results.

Participant milestones

Participant milestones
Measure
Esomeprazole
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Overall Study
STARTED
19
32
Overall Study
COMPLETED
18
28
Overall Study
NOT COMPLETED
1
4

Reasons for withdrawal

Reasons for withdrawal
Measure
Esomeprazole
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Overall Study
Withdrawal by Subject
0
1
Overall Study
Adverse Event
0
1
Overall Study
Study medication non-compliance
0
2
Overall Study
Incorrectly assigned to opposite arm
1
0

Baseline Characteristics

The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Esomeprazole
n=19 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=32 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Total
n=51 Participants
Total of all reporting groups
Age, Continuous
47.5 years
STANDARD_DEVIATION 14.9 • n=99 Participants
33.7 years
STANDARD_DEVIATION 10.4 • n=107 Participants
39 years
STANDARD_DEVIATION 13.9 • n=206 Participants
Sex: Female, Male
Female
7 Participants
n=99 Participants
13 Participants
n=107 Participants
20 Participants
n=206 Participants
Sex: Female, Male
Male
12 Participants
n=99 Participants
19 Participants
n=107 Participants
31 Participants
n=206 Participants
Region of Enrollment
United States
19 participants
n=99 Participants
32 participants
n=107 Participants
51 participants
n=206 Participants
Mean number of eosinophils per high powered field in esophagus
35.6 eos/hpf
STANDARD_DEVIATION 24.7 • n=99 Participants
46.7 eos/hpf
STANDARD_DEVIATION 26.5 • n=107 Participants
41.2 eos/hpf
STANDARD_DEVIATION 27.7 • n=206 Participants
Endoscopic evidence of GERD
Multiple rings (felinization or corrugations)
14 Participants
n=99 Participants
18 Participants
n=107 Participants
32 Participants
n=206 Participants
Endoscopic evidence of GERD
Hiatal hernia
15 Participants
n=99 Participants
10 Participants
n=107 Participants
25 Participants
n=206 Participants
Endoscopic evidence of GERD
Erosive esophagitis
7 Participants
n=99 Participants
2 Participants
n=107 Participants
9 Participants
n=206 Participants
Number of participants with frequent GERD/dysphagia symptoms
Frequent symptoms
15 participants
n=99 Participants
0 participants
n=107 Participants
15 participants
n=206 Participants
Number of participants with frequent GERD/dysphagia symptoms
No or infrequent symptoms
3 participants
n=99 Participants
17 participants
n=107 Participants
20 participants
n=206 Participants
Number of participants with frequent GERD/dysphagia symptoms
No symptoms
0 participants
n=99 Participants
15 participants
n=107 Participants
15 participants
n=206 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Subjects with Esophageal eosinophilia experiencing a histological response to treatment. Subjects were considered to have histological response to treatment if both sets of biopsies (from the distal and mid-esophagus) had, on average, less than 5 eosinophils per high power field (eos/hpf) at the 6-month biopsies.

Outcome measures

Outcome measures
Measure
Esomeprazole
n=18 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=28 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Histological Response to Treatment
Subjects with histological response
11 Participants
16 Participants
Histological Response to Treatment
Subjects with nonsignificant histological response
7 Participants
12 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Subjects with Esophageal eosinophilia experiencing a response in their dysphagia symptoms to treatment. Symptomatic improvement in symptoms was defined as a score of at least two levels lower than the baseline dysphagia symptom question on the Mayo Dysphagia Questionnaire-30 days (MDQ-30). Dysphagia symptoms were determined based on the MDQ-30 question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Patients must have marked a score of 3 or higher corresponding to 'Moderate, cannot be ignored, but does not affect my lifestyle' to be included in the study.

Outcome measures

Outcome measures
Measure
Esomeprazole
n=18 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=28 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Symptomatic Response to Treatment
Subjects with response in dysphagia symptoms
11 Participants
15 Participants
Symptomatic Response to Treatment
Subjects with no response in dysphagia symptoms
7 Participants
13 Participants

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: The analysis population includes only subjects with a histologic response. Subjects were considered to have a histological response to treatment if both sets of biopsies (from distal \& mid-esophagus) had, on average, less than 5 eos/hpf.

Dysphagia symptoms were determined based on the Mayo Dysphagia Questionnaire-30 days (MDQ-30), using the question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Symptomatic improvement was defined as only an improvement of 2 levels on this question.

Outcome measures

Outcome measures
Measure
Esomeprazole
n=11 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=16 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment
Dysphagia symptoms improved
5 Participants
11 Participants
Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment
Dysphagia symptoms did not improve
6 Participants
5 Participants

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: The analysis population for this item only included subjects with a non-significant histologic response. Subjects were considered to have a histological response to treatment if both sets of 6-month biopsies (from distal \& mid-esophagus) had, on average, less than 5 eos/hpf.

Dysphagia symptoms were determined based on the Mayo Dysphagia Questionnaire-30 days (MDQ-30), using the question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Patients must have marked a score of 3 or higher corresponding to 'Moderate, cannot be ignored, but does not affect my lifestyle' to be included in the study.

Outcome measures

Outcome measures
Measure
Esomeprazole
n=7 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=12 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment
Dysphagia symptoms responded to treatment
6 Participants
4 Participants
Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment
Dysphagia symptoms did not respond
1 Participants
8 Participants

SECONDARY outcome

Timeframe: Baseline, 6 months

Multiple concentric rings or furrows of the esophagus is an endoscopic finding traditionally ascribed to eosinophilic esophagitis.

Outcome measures

Outcome measures
Measure
Esomeprazole
n=18 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=28 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy
11 participants
17 participants

SECONDARY outcome

Timeframe: Baseline, 6 months

Outcome measures

Outcome measures
Measure
Esomeprazole
n=18 Participants
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=28 Participants
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Participants With Presence of Erosive Esophagitis at Six Month Endoscopy
1 participants
8 participants

Adverse Events

Esomeprazole

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Budesonide

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Esomeprazole
n=18 participants at risk
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
Budesonide
n=28 participants at risk
Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)
Immune system disorders
Hives
5.6%
1/18 • Number of events 1 • Baseline to 6 months
3.6%
1/28 • Number of events 1 • Baseline to 6 months

Additional Information

Dr. Amy Foxx-Orenstein, D.O., Associate Prof. of Medicine, College of Medicine

Mayo Clinic

Phone: 480-301-8806

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place