GERD
Conditions
Keywords
Gastroesophageal Reflux Disease, Acid Reflux
Brief summary
To compare the efficacy of three different long-term treatment strategies of reflux disease in primary care setting.
Interventions
DRUGesomeprazole (Nexium®)
This randomized study was conducted on parallel groups and included two phases: * One initial phase during when the patients received once daily, either esomeprazole 20 mg or esomeprazole 40 mg, depending on the investigator's decision * One maintenance treatment phase, patients were randomized to one of the following three groups, either esomeprazole 20 mg once daily, or esomeprazole 20 mg on demand or antacid treatment as needed
DRUGXolaam®
This randomized study was conducted on parallel groups and included two phases: * One initial phase during when the patients received once daily, either esomeprazole 20 mg or esomeprazole 40 mg, depending on the investigator's decision * One maintenance treatment phase, patients were randomized to one of the following three groups, either esomeprazole 20 mg once daily, or esomeprazole 20 mg on demand or antacid treatment as needed
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who seek medical advice in primary care for symptoms thought to be GERD related (GERD is a condition which develops when the reflux of stomach content causes troublesome symptoms and / or complications).
Exclusion criteria
* Subjects with any clinical GERD treatment (PPI, H2-receptor antagonists) within the last 3 months prior to Visit 1. * A history of severe esophagitis or known other complications, with alarm symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Three Strategies of Long-term Treatment | 16 weeks | Percentage of failure of maintenance treatment between V2 (4 weeks) and V3 (16 weeks) evaluated by the patient, defined based on responses to 2 questions (if at least 1 negative response was given, the patient was considered to be in failure) : Did the treatment produce sufficient control of reflux symptoms? Do you wish to continue the treatment? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Treatment With Low Dose Aspirin (Acetyl Salicylic Acid) Used Concomitantly During the Initial Phase and the Maintenance Phase | 4 weeks | No possibility to describe as only 2 patients took ASA |
| Differences Among Strategies of Maintenance Treatment for Satisfaction of the Patient, Using the GIS (Gord Impact Scale) Scale.(Change in Values of Score Derived From the GIS Questionnaire From V2 to V3 = Start to End of the Maintenance Phase) | 4 to 16 weeks | Change in values of upper digestive symptoms (GORD Impact Scale) from week 4 to week 16. Scale of 1 to 4 : 1 = every day, 2 = often, 3 = sometime, 4 = never) |
| Impact of Anxiety and Depression During the Initial Visit Measured by the HADS ( Hospital Anxiety and Depression Scale) Questionnaire on Response to Initial Treatment and to Maintenance Treatment | 16 weeks | Failure of treatment (as defined as in primary outcome measure) according to confirmed anxiety and depression during maintenance treatment evaluated by the patient via the score of HADS questionnaire. HADS scale ranges= 0 to 21 (the higher score, the worse : ≤7 : no anxiety-depression/ \[8-10\] : possible anxiety-depression/ \>10 : anxiety-depression) |
| Difference in Symptom Severity Evaluation Performed by the Investigators, When Symptom Severity is Assessed With and Without Reflux Disease Questionnaire (RDQ). | 4 weeks | Total percentage of subjects for whom evaluation of symptom severity using the Reflux Disease Questionnaire (RDQ) is different, either positively or negatively, as compared to clinical judgment made by Investigator. The RDQ Includes 12 Items: 6 Concern the Frequency of Symptoms Ranging From Never for the Lowest Frequency to Every Day for the Highest, 6 Others Assess the Severity of Symptoms From Not at All to Strong. The Total Score of the RDQ, Ranging From 0 to 40, is Obtained by Adding the Scores of Each Item. |
| Score Abacuses Based on the Reflux Disease Questionnaire (RDQ) Questionnaire | Day 0 | May be used to evaluate the severity of symptoms during the initial visit. Not done |
| Score Abacuses Based on the Reflux Disease Questionnaire (RDQ) | Week 4 | May be used to define the success of treatment. Not done |
| Number of Participants and Type of Serious Adverse Events and Adverse Events Leading to a Premature Discontinuation of the Study | 12 weeks - maintenance treatment phase | Number of participants with serious adverse events and adverse events leading to study treatment discontinuation. AE and SAE as defined in ICH-GCP. |
Countries
France
Participant flow
Recruitment details
Patients were recruited by general practitioner between March 1, 2007 and July 21, 2008
Pre-assignment details
The study included 2 phases (maximum treatment duration = 16 weeks): * one initial treatment phase of 4 weeks * one randomized maintenance treatment phase of 12 weeks only for patients whose initial treatment is considered to be successful at the end of the initial phase. Only maintenance phase data were reported in the Baseline module measures.
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole 20 mg Once Daily (Maintenance Phase) | 871 |
| Esomeprazole 20 mg on Demand (Maintenance Phase) | 857 |
| Antacid Treatment (Maintenance Phase) antacid treatment as needed (maintenance phase) (Xolaam® maximum six tablets per day) | 830 |
| Total | 2,558 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Maintenance Treatment Phase | Adverse Event | 0 | 0 | 3 | 2 | 13 |
| Maintenance Treatment Phase | Didn'r receive the treatment | 0 | 0 | 22 | 17 | 29 |
| Maintenance Treatment Phase | Ineffectiveness | 0 | 0 | 5 | 3 | 14 |
| Maintenance Treatment Phase | Lost to Follow-up | 0 | 0 | 8 | 14 | 10 |
| Maintenance Treatment Phase | Patient's wish | 0 | 0 | 19 | 9 | 20 |
| Maintenance Treatment Phase | Protocol specific criteria's development | 0 | 0 | 1 | 0 | 6 |
| Maintenance Treatment Phase | Protocol Violation | 0 | 0 | 103 | 88 | 87 |
Baseline characteristics
| Characteristic | Esomeprazole 20 mg Once Daily (Maintenance Phase) | Esomeprazole 20 mg on Demand (Maintenance Phase) | Antacid Treatment (Maintenance Phase) | Total |
|---|---|---|---|---|
| Age Continuous | 41.5 years STANDARD_DEVIATION 9.83 | 41.79 years STANDARD_DEVIATION 9.97 | 41.6 years STANDARD_DEVIATION 10 | 41.64 years STANDARD_DEVIATION 9.91 |
| Sex: Female, Male Female | 449 Participants | 415 Participants | 411 Participants | 1275 Participants |
| Sex: Female, Male Male | 422 Participants | 442 Participants | 419 Participants | 1283 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 2,156 | 16 / 873 | 5 / 886 | 2 / 880 | 13 / 851 |
| serious Total, serious adverse events | 8 / 2,156 | 2 / 873 | 2 / 886 | 3 / 880 | 4 / 851 |
Outcome results
Primary
Efficacy of Three Strategies of Long-term Treatment
Percentage of failure of maintenance treatment between V2 (4 weeks) and V3 (16 weeks) evaluated by the patient, defined based on responses to 2 questions (if at least 1 negative response was given, the patient was considered to be in failure) : Did the treatment produce sufficient control of reflux symptoms? Do you wish to continue the treatment?
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 20 mg Once Daily (Maintenance Phase) | Efficacy of Three Strategies of Long-term Treatment | 10.6 Percentage of participants with failure |
| Esomeprazole 20 mg on Demand (Maintenance Phase) | Efficacy of Three Strategies of Long-term Treatment | 7.8 Percentage of participants with failure |
| Antacid Treatment (Maintenance Phase) | Efficacy of Three Strategies of Long-term Treatment | 43 Percentage of participants with failure |
Secondary
Difference in Symptom Severity Evaluation Performed by the Investigators, When Symptom Severity is Assessed With and Without Reflux Disease Questionnaire (RDQ).
Total percentage of subjects for whom evaluation of symptom severity using the Reflux Disease Questionnaire (RDQ) is different, either positively or negatively, as compared to clinical judgment made by Investigator. The RDQ Includes 12 Items: 6 Concern the Frequency of Symptoms Ranging From Never for the Lowest Frequency to Every Day for the Highest, 6 Others Assess the Severity of Symptoms From Not at All to Strong. The Total Score of the RDQ, Ranging From 0 to 40, is Obtained by Adding the Scores of Each Item.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 20 mg Once Daily (Maintenance Phase) | Difference in Symptom Severity Evaluation Performed by the Investigators, When Symptom Severity is Assessed With and Without Reflux Disease Questionnaire (RDQ). | 3.7 Percentage of participants |
| Esomeprazole 20 mg on Demand (Maintenance Phase) | Difference in Symptom Severity Evaluation Performed by the Investigators, When Symptom Severity is Assessed With and Without Reflux Disease Questionnaire (RDQ). | 2.3 Percentage of participants |
Secondary
Differences Among Strategies of Maintenance Treatment for Satisfaction of the Patient, Using the GIS (Gord Impact Scale) Scale.(Change in Values of Score Derived From the GIS Questionnaire From V2 to V3 = Start to End of the Maintenance Phase)
Change in values of upper digestive symptoms (GORD Impact Scale) from week 4 to week 16. Scale of 1 to 4 : 1 = every day, 2 = often, 3 = sometime, 4 = never)
Time frame: 4 to 16 weeks
Population: 871 (-66 missing data, 801 (-56 missing data), 833 (-75 missing data)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antacid Treatment (Maintenance Phase) | Differences Among Strategies of Maintenance Treatment for Satisfaction of the Patient, Using the GIS (Gord Impact Scale) Scale.(Change in Values of Score Derived From the GIS Questionnaire From V2 to V3 = Start to End of the Maintenance Phase) | 0.12 Scores on scale | Standard Deviation 0.79 |
| Esomeprazole 20 mg on Demand (Maintenance Phase) | Differences Among Strategies of Maintenance Treatment for Satisfaction of the Patient, Using the GIS (Gord Impact Scale) Scale.(Change in Values of Score Derived From the GIS Questionnaire From V2 to V3 = Start to End of the Maintenance Phase) | 0.04 Scores on scale | Standard Deviation 0.73 |
| Antacid Treatment (Maintenance Phase) | Differences Among Strategies of Maintenance Treatment for Satisfaction of the Patient, Using the GIS (Gord Impact Scale) Scale.(Change in Values of Score Derived From the GIS Questionnaire From V2 to V3 = Start to End of the Maintenance Phase) | -0.22 Scores on scale | Standard Deviation 0.8 |
Secondary
Impact of Anxiety and Depression During the Initial Visit Measured by the HADS ( Hospital Anxiety and Depression Scale) Questionnaire on Response to Initial Treatment and to Maintenance Treatment
Failure of treatment (as defined as in primary outcome measure) according to confirmed anxiety and depression during maintenance treatment evaluated by the patient via the score of HADS questionnaire. HADS scale ranges= 0 to 21 (the higher score, the worse : ≤7 : no anxiety-depression/ \[8-10\] : possible anxiety-depression/ \>10 : anxiety-depression)
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antacid Treatment (Maintenance Phase) | Impact of Anxiety and Depression During the Initial Visit Measured by the HADS ( Hospital Anxiety and Depression Scale) Questionnaire on Response to Initial Treatment and to Maintenance Treatment | 9.8 Percent of participants with failure |
| Esomeprazole 20 mg on Demand (Maintenance Phase) | Impact of Anxiety and Depression During the Initial Visit Measured by the HADS ( Hospital Anxiety and Depression Scale) Questionnaire on Response to Initial Treatment and to Maintenance Treatment | 9.3 Percent of participants with failure |
| Antacid Treatment (Maintenance Phase) | Impact of Anxiety and Depression During the Initial Visit Measured by the HADS ( Hospital Anxiety and Depression Scale) Questionnaire on Response to Initial Treatment and to Maintenance Treatment | 43.7 Percent of participants with failure |
Secondary
Impact of Treatment With Low Dose Aspirin (Acetyl Salicylic Acid) Used Concomitantly During the Initial Phase and the Maintenance Phase
No possibility to describe as only 2 patients took ASA
Time frame: 4 weeks
Population: Outcome measure not possible to describe as only 2 patients took Aspirin.
Secondary
Number of Participants and Type of Serious Adverse Events and Adverse Events Leading to a Premature Discontinuation of the Study
Number of participants with serious adverse events and adverse events leading to study treatment discontinuation. AE and SAE as defined in ICH-GCP.
Time frame: 12 weeks - maintenance treatment phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antacid Treatment (Maintenance Phase) | Number of Participants and Type of Serious Adverse Events and Adverse Events Leading to a Premature Discontinuation of the Study | 5 Participants |
| Esomeprazole 20 mg on Demand (Maintenance Phase) | Number of Participants and Type of Serious Adverse Events and Adverse Events Leading to a Premature Discontinuation of the Study | 4 Participants |
| Antacid Treatment (Maintenance Phase) | Number of Participants and Type of Serious Adverse Events and Adverse Events Leading to a Premature Discontinuation of the Study | 15 Participants |
Secondary
Score Abacuses Based on the Reflux Disease Questionnaire (RDQ)
May be used to define the success of treatment. Not done
Time frame: Week 4
Population: The results of exploratory analyses are not available.
Secondary
Score Abacuses Based on the Reflux Disease Questionnaire (RDQ) Questionnaire
May be used to evaluate the severity of symptoms during the initial visit. Not done
Time frame: Day 0
Population: The results of exploratory analyses are not available.
Secondary
Score Abacuses Based on the Reflux Disease Questionnaire (RDQ) Questionnaire
May be used to offer patients a strategy of treatment during the initial phase and in the long term. Not done
Time frame: Day 0
Population: The results of exploratory analyses are not available.