Barrett's Esophagus
Conditions
Keywords
Barrett's Esophagus
Brief summary
The hypothesis of this study was that the comparative effectiveness of unsedated transnasal endoscopy (uTNE) will be greater than sedated endoscopy (sEGD) in population screening for BE.
Detailed description
Barrett's esophagus (BE), a well-known complication of Gastroesophageal Reflux (GER), is the strongest known precursor of esophageal adenocarcinoma. Thus, identifying effective screening approaches for the early detection of BE are highly desired. Current impediments to BE screening include 1) the inability to utilize sedated endoscopy (sEGD) effectively in populations and 2) current GER-based paradigms for detecting BE. Referral center studies demonstrate comparable accuracy between unsedated transnasal endoscopy (uTNE) and sEGD. However, patient acceptability and diagnostic yield with uTNE in general populations remain unknown. Using the Rochester, Minnesota Epidemiology Project resources, random samples of Olmsted County residents were drawn, and those subjects were mailed validated gastrointestinal symptom questionnaires. These surveys allowed identification of a cohort of community subjects well characterized by the frequency of reflux symptoms. Eligible subjects who were greater than or equal to 50 years old, and who had no previous history of endoscopic evaluation and who were not known to have BE were randomized, stratified by age, sex, and reflux symptoms, and assigned to one of the 3 arms of the study. Subjects in each arm who met the eligibility criteria were initially sent generic invitation letters asking if they agreed to be contacted by phone in two weeks' time to inform them about a research study. If potential subjects explicitly declined to be contacted they were excluded from the study. Eligible subjects were contacted by telephone and only offered the endoscopy technique they had been randomized to. Subjects who accepted and signed an informed consent document were treated according to their randomized assignment and all 3 groups were followed up in the same manner. Biopsies were taken from any endoscopically suspected BE and from the gastroesophageal junction and squamous mucosa in all subjects. The length of BE segment was defined using Prague criteria. All participants received a telephone call from the research coordinator 1 and 30 days after the procedure to complete validated tolerability scales and adverse events questionnaires.
Interventions
DEVICESedated Endoscopy
The sedated esophagogastroduodenoscopy procedures were performed using a conventional high-definition endoscope (GIF-180, Olympus America, Center Valley, Pennsylvania) under conscious sedation with intravenous midazolam and fentanyl.
DEVICETransnasal Endoscopy
Unsedated transnasal endoscopy performed using the EndoSheath transnasal esophagoscope (TNL-5000, Vision Sciences). Topical anesthetic aerosol spray was applied to the posterior pharynx and nasal spray mixture was applied to the patients nares 10-15 minutes before the endoscopy procedure.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Advancing Translational Sciences (NCATS)
American College of Gastroenterology
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 95 Years
Healthy volunteers
Yes
Inclusion criteria
* Olmsted county, Minnesota resident * Age 50 or older * Able to give informed consent
Exclusion criteria
* History of known Barretts Esophagus (BE) or endoscopy within the last 10 years * History of progressive dysphagia * Known Zenkers or epiphrenic diverticulum * History of recurrent epistaxis * Illnesses that impair ability to complete questionnaires (e.g. metastatic cancer, stroke, dementia) * Contraindication to esophageal biopsy (such as anticoagulation using warfarin or clopidogrel).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Agreed to Participated in the Esophageal Assessment | Approximately 2 weeks after invitation letter was sent | This outcome measure was defined as the proportion of subjects who agreed to undergo esophageal assessment in the three groups out of those who were eligible to be contacted for participation in screening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Evaluation | Visit 1 | The rate of complete evaluation was defined as visualization of the whole esophagus and identification of landmarks: squamocolumnar junction, gastroesophageal junction (upper margin of gastric folds with stomach deflated), and the diaphragmatic hiatus. The categories of evaluation were classified as complete (all three landmarks identified), incomplete (some landmarks identified), or unsuccessful. |
| Rate of Acquisition of Biopsies From the Esophagus | Visit 1 | — |
| Mean Duration of Procedure | Visit 1 | Duration of the procedure was defined as time from the beginning of the procedure (initiation of sedation or local anesthesia) to extubation. |
| Rate of Successful Intubation | Visit 1 | The rate of successful intubation was defined as the ability to traverse the upper esophageal sphincter and visualize the esophageal mucosa and classified as successful or unsuccessful. |
| Mean Tolerability Scores | Day 1 after the procedure | Validated pain scales (where 0 is none and 10 is severe) were used to assess the degree of pain, choking, gagging, and anxiety experienced during the procedure. Overall tolerance was rated on a scale from 0 to 10, where 0 is good, and 10 is poor tolerance. |
| Acceptability | Day 1 after the procedure | Acceptability was defined as the proportion of subjects willing to undergo the procedure again in the future. |
| Mean Time From Extubation to Discharge | Visit 1 | This outcome measures the recovery time after the procedure. |
Countries
United States
Participant flow
Recruitment details
Eligible participants were identified using the Rochester Epidemiology Project resources from Olmsted County, Minnesota residents. The study took place between 1 April 2011 and 30 October 2013.
Participants by arm
| Arm | Count |
|---|---|
| Sedated Endoscopy Sedated esophagogastroduodenoscopy with biopsy
Sedated Endoscopy: The sedated esophagogastroduodenoscopy procedures were performed using a conventional high-definition endoscope (GIF-180, Olympus America, Center Valley, Pennsylvania) under conscious sedation with intravenous midazolam and fentanyl. | 150 |
| Transnasal Endoscopy at Hospital Unit Unsedated transnasal endoscopy at hospital unit.
Transnasal Endoscopy: Unsedated transnasal endoscopy performed using the EndoSheath transnasal esophagoscope (TNL-5000, Vision Sciences). Topical anesthetic aerosol spray was applied to the posterior pharynx and nasal spray mixture was applied to the patients nares 10-15 minutes before the endoscopy procedure. | 151 |
| Transnasal Endoscopy at Mobile Unit Unsedated transnasal endoscopy in mobile research van
Transnasal Endoscopy: Unsedated transnasal endoscopy performed using the EndoSheath transnasal esophagoscope (TNL-5000, Vision Sciences). Topical anesthetic aerosol spray was applied to the posterior pharynx and nasal spray mixture was applied to the patients nares 10-15 minutes before the endoscopy procedure. | 158 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Declined | 78 | 63 | 62 |
| Overall Study | Unable to contact | 11 | 16 | 20 |
| Overall Study | Unable to intubate | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Sedated Endoscopy | Total | Transnasal Endoscopy at Mobile Unit | Transnasal Endoscopy at Hospital Unit |
|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 9 | 65 years STANDARD_DEVIATION 9 | 64 years STANDARD_DEVIATION 10 | 64 years STANDARD_DEVIATION 10 |
| Education College/professional training | 64 participants | 205 participants | 74 participants | 67 participants |
| Education High school or some college | 77 participants | 225 participants | 72 participants | 76 participants |
| Education Less than high school | 2 participants | 12 participants | 7 participants | 3 participants |
| Education Unknown/not answered | 7 participants | 17 participants | 5 participants | 5 participants |
| Employment Employed | 48 participants | 167 participants | 56 participants | 63 participants |
| Employment Retired | 87 participants | 248 participants | 86 participants | 75 participants |
| Employment Unemployed/homemaker | 8 participants | 27 participants | 11 participants | 8 participants |
| Employment Unknown/not answered | 7 participants | 17 participants | 5 participants | 5 participants |
| Marital Status Married | 115 participants | 349 participants | 116 participants | 118 participants |
| Marital Status Not married (single/widowed/divorced/separated) | 34 participants | 108 participants | 41 participants | 33 participants |
| Marital Status Unknown/not answered | 1 participants | 2 participants | 1 participants | 0 participants |
| Reflux Symptoms Heartburn or acid regurgitation < 1/week | 62 participants | 197 participants | 68 participants | 67 participants |
| Reflux Symptoms Heartburn or acid regurgitation > 1/week | 12 participants | 43 participants | 15 participants | 16 participants |
| Reflux Symptoms No heartburn or acid regurgitation | 76 participants | 219 participants | 75 participants | 68 participants |
| Region of Enrollment United States | 150 participants | 459 participants | 158 participants | 151 participants |
| Sex: Female, Male Female | 81 Participants | 250 Participants | 87 Participants | 82 Participants |
| Sex: Female, Male Male | 69 Participants | 209 Participants | 71 Participants | 69 Participants |
| Use of Proton Pump Inhibitor (PPI) No | 125 participants | 383 participants | 130 participants | 128 participants |
| Use of Proton Pump Inhibitor (PPI) Yes | 25 participants | 76 participants | 28 participants | 23 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 | 14 / 61 | 20 / 69 | 23 / 76 |
| serious Total, serious adverse events | 0 / 61 | 0 / 69 | 0 / 76 |
Outcome results
Primary
Percentage of Subjects Who Agreed to Participated in the Esophageal Assessment
This outcome measure was defined as the proportion of subjects who agreed to undergo esophageal assessment in the three groups out of those who were eligible to be contacted for participation in screening.
Time frame: Approximately 2 weeks after invitation letter was sent
Population: The analysis population for this outcome measure was the number of subjects per group who were eligible to contact.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sedated Endoscopy | Percentage of Subjects Who Agreed to Participated in the Esophageal Assessment | 40.7 percentage of participants |
| Transnasal Endoscopy at Hospital Unit | Percentage of Subjects Who Agreed to Participated in the Esophageal Assessment | 45.7 percentage of participants |
| Transnasal Endoscopy at Mobile Unit | Percentage of Subjects Who Agreed to Participated in the Esophageal Assessment | 47.5 percentage of participants |
p-value: 0.25Chi-squared
p-value: 0.42Chi-squared
p-value: 0.27Chi-squared
p-value: 0.82Chi-squared
Secondary
Acceptability
Acceptability was defined as the proportion of subjects willing to undergo the procedure again in the future.
Time frame: Day 1 after the procedure
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sedated Endoscopy | Acceptability | Acceptable | 93.4 percentage of participants |
| Sedated Endoscopy | Acceptability | Unacceptable | 6.6 percentage of participants |
| Transnasal Endoscopy at Hospital Unit | Acceptability | Acceptable | 83.3 percentage of participants |
| Transnasal Endoscopy at Hospital Unit | Acceptability | Unacceptable | 16.7 percentage of participants |
| Transnasal Endoscopy at Mobile Unit | Acceptability | Acceptable | 78.9 percentage of participants |
| Transnasal Endoscopy at Mobile Unit | Acceptability | Unacceptable | 21.1 percentage of participants |
p-value: 0.001Kruskal-Wallis
Secondary
Mean Duration of Procedure
Duration of the procedure was defined as time from the beginning of the procedure (initiation of sedation or local anesthesia) to extubation.
Time frame: Visit 1
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sedated Endoscopy | Mean Duration of Procedure | 9.3 minutes | Standard Deviation 1.6 |
| Transnasal Endoscopy at Hospital Unit | Mean Duration of Procedure | 8.0 minutes | Standard Deviation 2.7 |
| Transnasal Endoscopy at Mobile Unit | Mean Duration of Procedure | 8.5 minutes | Standard Deviation 2.5 |
p-value: <0.001Kruskal-Wallis
Secondary
Mean Time From Extubation to Discharge
This outcome measures the recovery time after the procedure.
Time frame: Visit 1
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sedated Endoscopy | Mean Time From Extubation to Discharge | 67.3 minutes | Standard Deviation 5.9 |
| Transnasal Endoscopy at Hospital Unit | Mean Time From Extubation to Discharge | 18.5 minutes | Standard Deviation 4.2 |
| Transnasal Endoscopy at Mobile Unit | Mean Time From Extubation to Discharge | 15.5 minutes | Standard Deviation 2.8 |
p-value: <0.001Kruskal-Wallis
Secondary
Mean Tolerability Scores
Validated pain scales (where 0 is none and 10 is severe) were used to assess the degree of pain, choking, gagging, and anxiety experienced during the procedure. Overall tolerance was rated on a scale from 0 to 10, where 0 is good, and 10 is poor tolerance.
Time frame: Day 1 after the procedure
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sedated Endoscopy | Mean Tolerability Scores | Overall Tolerance | 0.4 units on a scale | Standard Deviation 0.6 |
| Sedated Endoscopy | Mean Tolerability Scores | Gagging | 0.1 units on a scale | Standard Deviation 0.6 |
| Sedated Endoscopy | Mean Tolerability Scores | Choking | 0 units on a scale | Standard Deviation 0 |
| Sedated Endoscopy | Mean Tolerability Scores | Anxiety | 0.8 units on a scale | Standard Deviation 1.5 |
| Sedated Endoscopy | Mean Tolerability Scores | Pain | 0.1 units on a scale | Standard Deviation 0.5 |
| Transnasal Endoscopy at Hospital Unit | Mean Tolerability Scores | Anxiety | 2.3 units on a scale | Standard Deviation 2.2 |
| Transnasal Endoscopy at Hospital Unit | Mean Tolerability Scores | Overall Tolerance | 2.2 units on a scale | Standard Deviation 2.2 |
| Transnasal Endoscopy at Hospital Unit | Mean Tolerability Scores | Pain | 2.7 units on a scale | Standard Deviation 2.3 |
| Transnasal Endoscopy at Hospital Unit | Mean Tolerability Scores | Choking | 0.8 units on a scale | Standard Deviation 1.8 |
| Transnasal Endoscopy at Hospital Unit | Mean Tolerability Scores | Gagging | 1.2 units on a scale | Standard Deviation 2.4 |
| Transnasal Endoscopy at Mobile Unit | Mean Tolerability Scores | Pain | 3.2 units on a scale | Standard Deviation 8.8 |
| Transnasal Endoscopy at Mobile Unit | Mean Tolerability Scores | Overall Tolerance | 1.9 units on a scale | Standard Deviation 2.2 |
| Transnasal Endoscopy at Mobile Unit | Mean Tolerability Scores | Gagging | 1.3 units on a scale | Standard Deviation 2.3 |
| Transnasal Endoscopy at Mobile Unit | Mean Tolerability Scores | Anxiety | 2.8 units on a scale | Standard Deviation 2.8 |
| Transnasal Endoscopy at Mobile Unit | Mean Tolerability Scores | Choking | 0.6 units on a scale | Standard Deviation 1.9 |
Comparison: Comparison between the arms for pain scalep-value: <0.001Kruskal-Wallis
Comparison: Comparison between the arms for choking scalep-value: <0.001Kruskal-Wallis
Comparison: Comparison between the arms for gagging scalep-value: <0.001Kruskal-Wallis
Comparison: Comparison between the arms for anxiety scalep-value: <0.001Kruskal-Wallis
Comparison: Comparison between arms for overall tolerance scalep-value: <0.001Kruskal-Wallis
Secondary
Rate of Acquisition of Biopsies From the Esophagus
Time frame: Visit 1
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sedated Endoscopy | Rate of Acquisition of Biopsies From the Esophagus | Successful | 100 percentage of participants |
| Sedated Endoscopy | Rate of Acquisition of Biopsies From the Esophagus | Unsuccessful | 0 percentage of participants |
| Transnasal Endoscopy at Hospital Unit | Rate of Acquisition of Biopsies From the Esophagus | Successful | 83.3 percentage of participants |
| Transnasal Endoscopy at Hospital Unit | Rate of Acquisition of Biopsies From the Esophagus | Unsuccessful | 16.7 percentage of participants |
| Transnasal Endoscopy at Mobile Unit | Rate of Acquisition of Biopsies From the Esophagus | Successful | 79.0 percentage of participants |
| Transnasal Endoscopy at Mobile Unit | Rate of Acquisition of Biopsies From the Esophagus | Unsuccessful | 21 percentage of participants |
p-value: 0.001Kruskal-Wallis
Secondary
Rate of Complete Evaluation
The rate of complete evaluation was defined as visualization of the whole esophagus and identification of landmarks: squamocolumnar junction, gastroesophageal junction (upper margin of gastric folds with stomach deflated), and the diaphragmatic hiatus. The categories of evaluation were classified as complete (all three landmarks identified), incomplete (some landmarks identified), or unsuccessful.
Time frame: Visit 1
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sedated Endoscopy | Rate of Complete Evaluation | Incomplete | 0 procedures |
| Sedated Endoscopy | Rate of Complete Evaluation | Complete | 61 procedures |
| Sedated Endoscopy | Rate of Complete Evaluation | Unsuccessful | 0 procedures |
| Transnasal Endoscopy at Hospital Unit | Rate of Complete Evaluation | Incomplete | 0 procedures |
| Transnasal Endoscopy at Hospital Unit | Rate of Complete Evaluation | Complete | 69 procedures |
| Transnasal Endoscopy at Hospital Unit | Rate of Complete Evaluation | Unsuccessful | 3 procedures |
| Transnasal Endoscopy at Mobile Unit | Rate of Complete Evaluation | Complete | 75 procedures |
| Transnasal Endoscopy at Mobile Unit | Rate of Complete Evaluation | Unsuccessful | 0 procedures |
| Transnasal Endoscopy at Mobile Unit | Rate of Complete Evaluation | Incomplete | 1 procedures |
p-value: 0.08Fisher Exact
Secondary
Rate of Successful Intubation
The rate of successful intubation was defined as the ability to traverse the upper esophageal sphincter and visualize the esophageal mucosa and classified as successful or unsuccessful.
Time frame: Visit 1
Population: The analysis population included all subjects who agreed to undergo the esophageal assessment (intent to treat).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sedated Endoscopy | Rate of Successful Intubation | 100 percentage of participants |
| Transnasal Endoscopy at Hospital Unit | Rate of Successful Intubation | 95.8 percentage of participants |
| Transnasal Endoscopy at Mobile Unit | Rate of Successful Intubation | 100 percentage of participants |
p-value: 0.06Kruskal-Wallis