The EndoGastric Solutions TEMPO Trial

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of Transoral Incisionless Fundoplication (TIF) performed with EsophyX as compared to proton pump inhibitor (PPI) therapy for the treatment of chronic Gastroesophageal Reflux Disease (GERD) patients with refractory symptoms on Proton Pump Inhibitors (PPIs).

Detailed Description
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The objective of this study is to assess the efficacy and safety of TIF performed with EsophyX as compared to proton pump inhibitor (PPI) therapy for the treatment of chronic GERD patients with medically refractory GERD symptoms other than heartburn. Primary hypothesis: TIF will be superior to PPIs in eliminating or significantly improving daily bothersome GERD symptoms and/or troublesome regurgitation, if present, at 6-month follow-up. Secondary hypotheses: TIF will be superior to PPIs in eliminating or significantly improving daily bothersome GERD symptoms and/or troublesome regurgitation, if present, at 12-, 24-, 36-, 48- and 60-month follow-up. The majority of surgical patients will have normalized or 50% improved esophageal acid exposure compared to baseline at 6-month follow-up. The majority of surgical patients will be completely off PPIs at 6-, 12-, 24-, 36-, 48- and 60-month follow-up compared to baseline. The majority of crossover patients will be completely off PPIs at 6-, 18-, 30-, 42- and 54-month follow-up compared to baseline. A statistically greater proportion of crossover patients treated with TIF will be free of daily bothersome symptom(s) or will experience clinically significant improvement at 6-, 18-, 30-, 42- and 54-month follow-up.

Official Title
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Transoral Incisionless Fundoplication (TIF) Versus Medical Proton Pump Inhibitor (PPI) Management of Refractory Gastroesophageal Reflux Disease (GERD) Symptoms

Conditions
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Gastroesophageal Reflux Disease (GERD)

Intervention / Treatment
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* Device: EsophyX System with SerosaFuse fasteners
* Drug: PPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years; GERD for > 1 year; History of daily PPIs for > 6 months; At least daily bothersome medically refractory GERD symptom(s) other than heartburn on PPIs; Hill grade I and II at gastroesophageal junction; Proven gastroesophageal reflux by either endoscopy, ambulatory pH or barium swallow testing; Willingness to undergo pH testing; Willingness to cooperate with the postoperative diet; Availability for follow-up visits at 6, 12, 24, and 36 months; Willingly and cognitively signed inform consent Exclusion Criteria: BMI > 35 Hiatal hernia > 2c m in axial height and > 2 cm in greatest transverse dimension; Esophagitis grade C and D; Barrett's esophagus > 2 cm; Esophageal ulcer; Fixed esophageal stricture or narrowing; Portal hypertension and/or varices; Active gastro-duodenal ulcer disease; Gastric outlet obstruction or stenosis; Gastroparesis; Coagulation disorders; History of any of the following: resective gastric or esophageal surgery, antireflux surgery with anatomy unsuitable for TIF procedure per physician judgment, cervical spine fusion, Zenker's diverticulum, esophageal epiphrenic diverticulum, achalasia, scleroderma or dermatomyositis, eosinophilic esophagitis, or cirrhosis; Pregnancy or plans of pregnancy in the next 12 months; Enrollment in another device or drug study that may confound the results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Transoral incisionless esophago-gastric fundoplication using the EsophyX system with SerosaFuse fasteners (EndoGastric Solutions, Inc., Redmond, WA, USA) and following TIF2.0 protocol. | Device: EsophyX System with SerosaFuse fasteners<br>* Transoral Incisionless Fundoplication (TIF)/Transoral incisionless esophago-gastric fundoplication using the EsophyX System with SerosaFuse fasteners<br>|
| Active Comparator: Control<br>Patients who are dependent upon daily PPIs will continue on single dose twice daily or increase to single dose twice daily for the first six months of the clinical trial. Patients will be offered TIF crossover procedure upon completion of month-6 follow-up visit. | Drug: PPI<br>* Control Arm participants will take maximum standard dose of PPI during Initial Study period<br>* Other names: same brand of PPI used by all Control Arm participants;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting GERD (Gastroesophageal Reflux Disease) Symptom Elimination or Clinically Significant Improvement Evaluated by RSI (Reflux Symptom Index) and RDQ (Reflux Disease Questionnaire). | 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. | 6 months | 
| Number of Participants Reporting Elimination of Daily Troublesome Regurgitation Using a Validated Questionnaire for Assessment | 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete PPI Discontinuation Assessed Using Validated Questionnaires and Participant-reported Discontinuation | 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. | 6 Months | 
| Number of Participants With Normalization of Esophageal Acid Exposure Assessed Using 48-hour pH Metry | 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 | 6 Months | 
| Number of Participants With Complete Healing or Reduction of Reflux Esophagitis, Assessed by EGD Using Los Angeles (LA) Grading | 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. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TEMPO, TIF, Transoral Incisionless Fundoplication, EsophyX System, refractory symptoms, proton pump inhibitors, EndoGastric Solutions, EGS, Acid Reflux, Heartburn, Regurgitation