Gastro-oesophageal Reflux
Conditions
Keywords
Gastroesophageal Reflux, Heartburn, Proton pump inhibitor, GORD
Brief summary
The primary objective of this study is to compare, the number of patients with heartburn and regurgitation symptom resolution after treatment with either rabeprazole 20 mg, esomeprazole 20 mg or esomeprazole 40 mg.
Detailed description
The study is designed to be conducted in a realistic General Practice (GP) setting, enrolling typical Gastro-oesophageal Reflux Disease (GORD) patients that present for treatment, and for whom a Proton Pump Inhibitor (PPI) would normally be prescribed. The study will be conducted over a 4-week period on the basis that current GP standard practice is to treat the GORD patient for a period of 4-weeks prior to reassessment and further follow-up if required. This study is conducted in patients with GORD - associated heartburn (with or without regurgitation) at multiple GP centers, treatment is assigned based on chance (randomized), similar to the toss of a coin and neither doctor or patient knows which treatment they will receive (double-blinded). Following screening to determine eligibility, patients will be randomized to receive oral treatment with either, 20 mg rabeprazole, 20 mg esomeprazole or 40 mg esomeprazole once daily for 4 weeks. This 4-week study encompasses 2 protocol-mandated visits (baseline on day 0 and final visit on day 28). It is hypothesized that rabeprazole 20 mg will be no less effective than (non-inferior) esomeprazole 40 mg for the degree of GORD symptom resolution. Patients will take one tablet (rabeprazole 20 mg or placebo) and one capsule (esomeprazole 20 mg, esomeprazole 40 mg or placebo) each day for 28 days. The study medication will be taken once daily in the morning before breakfast, except the first dose, which will be taken during Visit 1.
Interventions
DRUGEsomeprazole
20mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily
DRUGRabeprazole
20mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily
Sponsors
Janssen-Cilag Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Heartburn (defined as a feeling of burning or pain, rising from the epigastrium or lower part of the chest up towards the neck) with or without regurgitation * Patients must have had episodes of heartburn with or without regurgitation for 3 months or longer, and for \>= 3 days in the 7 days prior to randomisation * Able to understand and complete questionnaires, able to give written informed consent, and have access to a telephone
Exclusion criteria
* Patients requiring endoscopy within 4 weeks of randomisation or with gastrointestinal symptoms that, in the opinion of the investigator, require further investigation prior to or coincident with initiation of PPI therapy which would include, but are not limited to, alarm symptoms such as unintentional weight loss, progressive difficulty swallowing (dysphagia), iron deficiency anaemia and epigastric mass * Significant gastrointestinal obstruction, major gastric or oesophageal surgery (excluding appendectomy or cholecystectomy), oesophageal stricture or pyloric stenosis, extra-oesophageal manifestations of reflux disease * Patients with Barrett's oesophagus (\>3cm), Zollinger-Ellison Syndrome, scleroderma, malignancy (other than non-melanoma skin cancers) present within the last 5 years, hypersensitivity to rabeprazole or esomeprazole or any PPI, or any other significant condition that, in the opinion of the investigator, could interfere with the patients participation or compliance in the study such as past or current history of alcohol or drug abuse, hepatic, renal, pulmonary, respiratory abnormalities, or who have participated in an investigational drug or investigational device study within 30 days prior to the baseline visit or who are expected to do so during the 4 week study period * Female patients who are currently pregnant or breast feeding, or who, in the opinion of the investigator, may become pregnant throughout the study * Use of histamine-2 receptor antagonists (H2RAs) within 7 days of randomisation, anticholinergics, cholinergics, spasmolytics, opiates, sucralfate, proton pump inhibitors (PPIs), prokinetics, antibiotics (in relation to H. pylori treatment) or bismuth compounds within 14 days of randomisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With Complete Resolution of Heartburn by Week 4 | week 4 of treatment | Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe. |
| The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4 | 4 weeks | Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe. |
| The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4 | 4 weeks | Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild) assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe. |
| The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4 | 4 weeks | Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild)assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe. |
Secondary
| Measure | Time frame |
|---|---|
| The Median Time to Complete Relief of Regurgitation Symptoms | 4 weeks |
| The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods | 4 weeks |
| The Median Time to Complete Resolution of Heartburn Symptoms. | week 4 of treatment |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rabeprazole 20 mg/Day Rabeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily | 464 |
| Esomeprazole 40 mg/Day Esomeprazole 40 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily | 469 |
| Esomeprazole 20 mg/Day Esomeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily | 459 |
| Total | 1,392 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 22 | 27 | 16 |
| Overall Study | Lost to Follow-up | 29 | 19 | 20 |
| Overall Study | Patient discontinued and other reasons | 17 | 17 | 23 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Rabeprazole 20 mg/Day | Esomeprazole 40 mg/Day | Esomeprazole 20 mg/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 45.8 years STANDARD_DEVIATION 14.8 | 48 years STANDARD_DEVIATION 14.7 | 46.2 years STANDARD_DEVIATION 14.8 | 46.7 years STANDARD_DEVIATION 14.8 |
| Region of Enrollment Australia | 464 participants | 469 participants | 459 participants | 1392 participants |
| Sex: Female, Male Female | 204 Participants | 208 Participants | 208 Participants | 620 Participants |
| Sex: Female, Male Male | 260 Participants | 261 Participants | 251 Participants | 772 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 151 / 464 | 155 / 469 | 158 / 459 |
| serious Total, serious adverse events | 5 / 464 | 1 / 469 | 9 / 459 |
Outcome results
Primary
The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4
Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4 | 281 participants |
| Esomeprazole 40 mg/Day | The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4 | 283 participants |
| Esomeprazole 20 mg/Day | The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4 | 276 participants |
Comparison: Primary endpoints were assessed using non-inferiority tests. See below.p-value: <0.05non-inferiority
Primary
The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4
Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild) assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe.
Time frame: 4 weeks
Population: Symptom scores 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4 | 405 participants |
| Esomeprazole 40 mg/Day | The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4 | 418 participants |
| Esomeprazole 20 mg/Day | The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4 | 414 participants |
Comparison: Primary endpoints were assessed using non-inferiority tests. See below.p-value: <0.05non-inferiority
Primary
The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4
Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild)assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4 | 397 participants |
| Esomeprazole 40 mg/Day | The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4 | 413 participants |
| Esomeprazole 20 mg/Day | The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4 | 402 participants |
Comparison: Primary endpoints were assessed using non-inferiority tests. See below.p-value: <0.05non-inferiority
Primary
The Number of Patients With Complete Resolution of Heartburn by Week 4
Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe.
Time frame: week 4 of treatment
Population: The intent-to-treat (ITT) population was used for all efficacy analyses. The data were reanalysed using the compliance population (defined as all subjects who consumed at least 80% of study medication and who completed at least 80% of data recording).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Number of Patients With Complete Resolution of Heartburn by Week 4 | 272 participants |
| Esomeprazole 40 mg/Day | The Number of Patients With Complete Resolution of Heartburn by Week 4 | 302 participants |
| Esomeprazole 20 mg/Day | The Number of Patients With Complete Resolution of Heartburn by Week 4 | 278 participants |
Comparison: Primary endpoints were assessed using non-inferiority tests. See below.p-value: <0.05Non-inferiority
Secondary
The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods | 56.3 percent of participants |
| Esomeprazole 40 mg/Day | The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods | 63.4 percent of participants |
| Esomeprazole 20 mg/Day | The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods | 56.1 percent of participants |
Secondary
The Median Time to Complete Relief of Regurgitation Symptoms
Time frame: 4 weeks
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Median Time to Complete Relief of Regurgitation Symptoms | 9 days |
| Esomeprazole 40 mg/Day | The Median Time to Complete Relief of Regurgitation Symptoms | 11 days |
| Esomeprazole 20 mg/Day | The Median Time to Complete Relief of Regurgitation Symptoms | 13 days |
Secondary
The Median Time to Complete Resolution of Heartburn Symptoms.
Time frame: week 4 of treatment
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rabeprazole 20 mg/Day | The Median Time to Complete Resolution of Heartburn Symptoms. | 11 days |
| Esomeprazole 40 mg/Day | The Median Time to Complete Resolution of Heartburn Symptoms. | 9 days |
| Esomeprazole 20 mg/Day | The Median Time to Complete Resolution of Heartburn Symptoms. | 12 days |