The EndoGastric Solutions TEMPO Trial

Elimination or clinically significant improvement in troublesome regurgitation refractory to PPIs as evaluated by the disease-specific and validated instrument, Reflux Disease Questionnaire (RDQ):12-item questionnaire assesses frequency and severity of heartburn (4 items measure frequency and severity of pain and burning behind breastbone), regurgitation (4 items measuring the frequency and severity of acid taste in mouth and movement of material upward from stomach), and dyspeptic complaints (4 items measure frequency and severity of pain or burning in upper stomach). Responses range from 0 (not present) to 5 (daily) for frequency and 0 (not present) to 5 (severe) for severity. Patient's score is calculated as the mean of item responses with higher scores indicating more severe or frequent symptoms. A frequency score of 3 or more and severity score of 2 or more for the regurgitation questions were required to meet the Montreal consensus criteria for troublesome regurgitation.

Time frame: 6 months

Elimination or clinically significant improvement in GERD symptoms, other than heartburn, refractory to PPI, evaluated by Reflux Symptom Index (RSI):9-item questionnaire measures atypical symptoms: hoarseness, throat clearing, excess throat mucus, dysphagia, cough. Scale for each item ranges from 0 (no problem) to 5 (severe), with max total score of 45, normality threshold of ≤13. Reflux Disease Questionnaire (RDQ):12-item questionnaire to assess frequency and severity of heartburn (4 items measure frequency/severity of pain and burning behind breastbone), regurgitation (4 items measure frequency/severity of acid taste in mouth and movement of material upward from stomach), and dyspeptic complaints (4 items measure frequency and severity of pain or burning in upper stomach). Responses from 0 (not present) to 5 (daily) for frequency and 0 (not present) to 5 (severe) for severity. Scores calculated as mean of item responses with higher scores indicating more severe or frequent symptoms.

Time frame: 6 months

Esophagitis graded using the LA grading system through endoscopic visualization. Data entered represents study participants with complete healing or reduction in reflux esophagitis compared to baseline results. Note that Control arm patients were assessed while on PPIs. LA grades are A, B, C, D, with A being the least severe. Grade D was an exclusion criteria. Normal has no associated grade.

Time frame: 6 months

Elimination of daily bothersome GERD (Gastro Esophageal Reflux Disease) HRQL symptoms, using RDQ (Reflux Disease Questionnaire), RSI (Reflux Symptom Index) and as measured by complete discontinuation of PPI (Proton Pump Inhibitors) therapy at 6-month follow-up.

Time frame: 6 Months

Assessment of esophageal acid exposure with normal defined as pH\<4 in less than 5.3% total time exposure, using 48hr pH metry, with patients off PPIs for at least 7 days

Time frame: 6 Months

Number of patients reporting complete cessation of daily PPI therapy at 12 months post TIF and 6 months post Crossover TIF. This is patient-reported.

Time frame: 12 months

Assessment of the number of patients reporting elimination of troublesome regurgitation using the validated Reflux Disease Questionnaire (RDQ), a 12-item questionnaire to assess frequency and severity of heartburn (4 items measure frequency/severity of pain and burning behind breastbone), regurgitation (4 items measure frequency/severity of acid taste in mouth and movement of material upward from stomach), and dyspeptic complaints (4 items measure frequency and severity of pain or burning in upper stomach). Responses from 0 (not present) to 5 (daily) for frequency and 0 (not present) to 5 (severe) for severity. A frequency score of three or more and severity score of two or more for the regurgitation questions were required to meet the Montreal consensus criteria for troublesome regurgitation. The cohort of patients reported includes Treatment arm patients and Crossover patients combined as one group. Crossover patients included in the cohort are 30 months post TIF.

Time frame: 36 months

Population: Extended Follow-up Phase will place all patients into one cohort, combining Treatment and Control arm patients. All become Treatment patients so Control arm number of participants becomes 0.

Assessment of the number of patients reporting elimination of troublesome regurgitation using the validated Reflux Disease Questionnaire (RDQ), a 12-item questionnaire to assess frequency and severity of heartburn (4 items measure frequency/severity of pain and burning behind breastbone), regurgitation (4 items measure frequency/severity of acid taste in mouth and movement of material upward from stomach), and dyspeptic complaints (4 items measure frequency and severity of pain or burning in upper stomach). Responses from 0 (not present) to 5 (daily) for frequency and 0 (not present) to 5 (severe) for severity A frequency score of three or more and severity score of two or more for the regurgitation questions were required to meet the Montreal consensus criteria for troublesome regurgitation. The lower the score the better the outcome. (Crossover patients are 6-months post TIF.)

Time frame: 12 months

Satisfaction with current health condition OFF PPIs is reported as part of the GERD health-related quality of life questionnaire (GERD-HRQL), with 3 possible answers: satisfied, neutral or dissatisfied. 60 months post TIF, 54 months post Crossover.

Time frame: 60 months

Population: Overall Number of Participants Analyzed entered in Treatment arm includes all Control/crossover arm patients available for follow up. Control/crossover patients are at 54 month post-TIF follow up.

Reoperations completed post TIF by the end of 60 month (54 months post Crossover) follow up. These included 2 Laparoscopic Nissen fundoplications and 1 Dor fundoplication, completed without difficulty. This number includes the two reoperations reported and included in number of participants analyzed, at 36 month follow up.

Time frame: 60 months

Population: All participants are included in the Overall Number of Participants Analyzed, under the Treatment arm section; reported as 1 cohort.

Number of patients reporting complete cessation of daily PPI therapy at 36 months post TIF and 30 months post Crossover TIF combined into a single cohort.

Time frame: 36 months

Population: Treatment and Control/Crossover patients are reported as a single cohort at this follow-up period.

Elimination of daily bothersome heartburn as measured by GERD-HRQL (Gastro Esophageal Reflux Disease - Health-Related Quality of Life) questionnaire. GERD-HRQL is a validated questionnaire used to assess typical GERD symptoms by measuring 10 items on the visual analog scale ranging from 0 (no symptoms) to 5 (worst symptoms). A higher total GERD-HRQL score (range from 0 to 50) indicates more severe GERD. Note Control Arm patients are assessed while on standard daily dose of PPIs.

Time frame: 6 months

Number of patients reporting elimination of troublesome regurgitation using the validated Reflux Disease Questionnaire (RDQ), a 12-item questionnaire to assess frequency and severity of heartburn (4 items measure frequency/severity of pain and burning behind breastbone), regurgitation (4 items measuring frequency/severity of acid taste in mouth and movement of material upward from stomach), and dyspeptic complaints (4 items measure frequency/severity of pain or burning in upper stomach). 9 response options range from 0 (not present) to 5 (daily) for frequency and 0 (not present) to 5 (severe) for severity. Each patient's score is calculated as the mean of item responses, with higher scores indicating more frequent and/or severe symptoms. Cohort of patients reported at this time period includes Treatment arm patients and Control/Crossover patients combined as 1 group. Control/Crossover patients included in cohort are at 54 months post TIF.

Time frame: 60 months

Population: There were 44 patients available for follow up at 5 years post TIF. 43 were analyzed for regurgitation.~Treatment and Control/Crossover patients were combined into one cohort, shown in Treatment arm. Control arm value is 0. Control/crossover patients are at 54 months post TIF.

Assess number of patients reporting global elimination of troublesome regurgitation and atypical symptoms using Reflux Disease Questionnaire (RDQ), a 12-item questionnaire to assess frequency and severity of heartburn (4 items measure frequency/severity of pain and burning behind breastbone), regurgitation (4 items measure frequency/severity of acid taste in mouth and movement of material upward from stomach), and dyspeptic complaints (4 items measure frequency and severity of pain or burning in upper stomach). Responses from 0 (not present) to 5 (daily) for frequency and 0 (not present) to 5 (severe) for severity, and Reflux Symptom Index (RSI), a 9-item questionnaire to assess atypical symptoms: hoarseness, throat clearing, excess throat mucus, dysphagia, cough. Scale for each item ranges from 0 (no problem) to 5 (severe), with max score of 45, normality threshold of ≤13. Scores calculated as mean of item responses with higher scores indicating more severe or frequent symptoms.

Time frame: 12 months

Assessment of number of participants reporting healed esophagitis after TIF using EGD and LA grading system, LA grade A, B, C, D, with A meaning least severe esophagitis. No grade means normal. 30 months post TIF for Crossover patients.

Time frame: 36 months

Population: Control/Crossover patients have been added to the Treatment arm patients to make one combined cohort of patients. Control/Crossover patients are at 30 months post TIF.

Assessment of number of participants reporting healed esophagitis after TIF using EGD and LA grading system. Treatment arm patients assessed at 12 month post TIF and Control arm patients are at 6 month post Crossover TIF (12 month post randomization). LA grading A, B, C, D, with A the least severe esophagitis. No grade listed is Normal. Grade D is an exclusion criteria.

Time frame: 12 months

Assessment of esophageal acid exposure with normal defined as pH\<4 in less than 5.3% total time exposure, using 48hr pH metry, with patients off PPIs for at least 7 days.

Time frame: 12 months

Assessment of esophageal acid exposure with normal defined as pH\<4 in less than 5.3% total time exposure, using 48hr pH metry, with patients off PPIs for at least 7 days. Note that patients originally in the Control/Crossover arm are at 30 months post TIF at this follow up period. Treatment and Control/Crossover patients are reported as a single cohort.

Time frame: 36 months

Population: All patients are reported as one cohort, under the Treatment arm. Control arm number of participants analyzed will be 0. All are included in Overall Number in Treatment arm section.

Number of participants with complete cessation of daily PPI use, self-reported by patient at 60 month follow-up. (54 months for Control/crossover patients). Note: all patients were on daily PPIs at screening (100%).

Time frame: 60 months

Population: One cohort of patients entered as Overall number of Participants Analyzed, in Treatment arm section. Includes all available Control/crossover patients at 54 month post TIF follow up.

Satisfaction with current health condition OFF PPIs is reported as part of the GERD health-related quality of life questionnaire (GERD-HRQL), with 3 possible answers: satisfied, neutral or dissatisfied.

Time frame: 36 months

Population: All patients included in one cohort, entered in the treatment arm section

Number of patients with elimination of troublesome GERD symptoms using Reflux Symptom Index (RSI), a 9-item validated questionnaire to measure atypical GERD symptoms such as hoarseness, throat clearing, excess throat mucus, dysphagia, and cough. The scale for each individual item ranges from 0 (no problem) to 5 (severe problem), with a maximum total score of 45 and a normality threshold of ≤13. The lower the score, the better the outcome.

Time frame: 60 months

Population: Control/crossover patients are included in overall number of patients analyzed and entered in Treatment arm section to make one cohort. Crossover patients are at 54 month post TIF follow up.

Assessment of atypical GERD symptoms (symptoms other than heartburn) using validated Reflux Symptom Index (RSI), a 9 item questionnaire with a 0-5 score for each, for a total of 45, and a normality threshold of ≤13. The lower the score the better the outcome. Control/Crossover arm patients included in this cohort are at 30 months post TIF.

Time frame: 36 months

Population: Control/Crossover arm patients are included in the overall number of participants analyzed under the Treatment arm section, so Control arm number will be 0.