Barrett EsophagusNCT00282672
Ablation of Intestinal Metaplasia Containing Dysplasia
A study testing Ablation System plus anti-secretory medication in people with Barrett Esophagus, run by Medtronic - MITG at 19 sites in United States.
Trial summary
The purpose of this study is to determine if the intervention of a 510(k)-cleared endoscopically-guided (Halo Ablation systems), ablation system plus anti-secretory therapy is better than anti-secretory therapy alone in clearing Barrett's Esophagus. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Barrett Esophagus
- What is being tested?
- Ablation System plus anti-secretory medication
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 19 sitesUnited States
- Study dates
- Feb 2006to Aug 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria:1.Subject is 18-80 years of age, inclusive. 2.Subject has documented diagnosis of IM, maximum endoscopic length of 8 cm (as measured endoscopically from the TGF to the most proximal extent of the IM; i.e. TGF-TIM containing dysplasia as follows:
- For LGD:i.LGD documented on biopsy within previous 12 months from enrollment while subject on PPI therapy. ii.Histology slides reviewed at central pathology service for trial confirm LGD on first confirmatory central pathology review or, if necessary, confirm LGD on a tie-breaker review by a second pathologist.
- For HGD:i.Regular, non-nodular, non-ulcerated mucosa. ii.HGD documented on biopsy within previous 6 months from enrollment. iii.Histology slides reviewed at central pathology service for Trial confirm HGD on first confirmatory review or, if necessary, confirm HGD on a tie-breaker review by a second pathologist. iv.Baseline EUS within previous 12 months; 1.Catheter-based EUS excludes suspicious thickened Barrett's areas or, if suspicious areas found, prompts stacked biopsies of thickened area, the results of which do not render subject ineligible for enrollment. 3.For subjects with EMR history,the documented diagnosis of IM with dysplasia meets criterion #2 from biopsies collected either after the EMR procedure or during the EMR procedure but not from the EMR site. 4.Subject able to take oral proton pump inhibitor medication. 5.Subject able to discontinue aspirin and/or non-steroidal anti-inflammatory medications 7 days before and after all ablation procedures. 6.For female subjects of childbearing potential, a negative pregnancy test within 2 weeks of randomization. 7.Subject eligible for treatment and follow-up endoscopy and biopsy as required by the Protocol. 8.Subject willing to provide written, informed consent to participate in this clinical study and understands the responsibilities of trial participation. Exclusion Criteria:1.The subject is pregnant or planning a pregnancy during the study period. 2.Esophageal stricture preventing passage of endoscope or catheter. 3.Active esophagitis described as erosions or ulcerations encompassing more than 10% of distal esophagus. 4.Any history of malignancy of the esophagus. 5.Prior radiation therapy to the esophagus,except head and neck region radiation therapy. 6.Any previous ablative therapy within the esophagus (PDT, MPEC, APC, laser treatment, other). 7.History of EMR that meets any of the following criteria:a.EMR performed less than 8 weeks prior to the randomization endoscopy encounter b.EMR performed in a wide field manner (encompassing more than 90 degrees of any area of the esophagus.
8.Any previous esophageal surgery, including except fundoplication without complications (i.e. no slippage, dysphagia, etc).
9.Evidence of esophageal varices during treatment endoscopy. 10.Report of uncontrolled coagulopathy with international normalized ratio (INR) > 1.3 or platelet count <75,000 platelets per µL 11.Subject has a life-expectancy of less than two years due to an underlying medical condition.
12.Subject has a known history of unresolved drug or alcohol dependency that would limit ability to comprehend or follow instructions related to informed consent, post-treatment instructions, or follow-up guidelines.
13.Subject has an implantable pacing device (examples; AICD, neurostimulator, cardiac pacemaker)and has not received clearance for enrollment in this study by specialist responsible for the pacing device.
14.The subject is currently enrolled in an investigational drug or device trial that clinically interferes with the AIM Dysplasia Trial endpoints.
15.Subject suffers from psychiatric or other illness deemed by the investigator as an inability to comply with protocol.
For the 5 year extension, patient must have:1. Enrolled in the B-204 protocol. 2. Completed 1 year follow-up. 3. Completed 2 year follow-up.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
UNC Center for Functional GI & Motility Disorders
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
VAMC Dallas
Dallas, Texas, 75216
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
University of Kansas School of Medicine - Veterans Affairs Medical Center
Kansas City, Missouri, 64128
Gastrointestinal Associates
Knoxville, Tennessee, 37909
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Columbia University Medical Center
New York, New York, 10032
UC Irvine Medical Center
Orange, California, 92868
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Oregon Health Sciences University
Portland, Oregon, 97239
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
Washington University School of Medicine
St Louis, Missouri, 63110
Tacoma Digestive Disease Research Center
Tacoma, Washington, 98405
University of Arizona, VAMC
Tucson, Arizona, 85723
Harvard, VA Boston Healthcare W Roxbury
West Roxbury, Massachusetts, 02132
About this study
Official title: Ablation of Intestinal Metaplasia Containing Dysplasia (AIM Dysplasia Trial) A Multi-center, Randomized, Sham-Controlled Trial: Protocol Amendment to Extend Follow-up to 5 Years
The purpose of this study is to determine if the intervention of a 510(k)-cleared endoscopically-guided (Halo Ablation systems), ablation system plus anti-secretory therapy is better than anti-secretory therapy alone in clearing Barrett's Esophagus.
Read the detailed description
Barrett's esophagus or intestinal metaplasia (IM) is a change in the epithelial lining of the esophagus. Barrett's esophagus develops as a result of chronic exposure of the esophagus to refluxed stomach acid and enzymes, as well as bile, resulting in recurrent mucosal injury. Injury is accompanied by inflammation and, ultimately, a cellular change (metaplasia) to a specialized columnar epithelium (Spechler SJ. Barrett's Esophagus. N Engl J Med 2002;346(11):836-842.)
Patients who have a diagnosis of Barrett's esophagus typically undergo surveillance endoscopy every 1-3 years with multiple biopsy specimens obtained to facilitate early detection of progression of IM to dysplasia (more severe precancerous changes) and adenocarcinoma. (Sampliner RE. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastro 2002;97:1888-1895.) Progression of IM to low-grade dysplasia (LGD) indicates that cells exhibit more "cancer-like" architecture, thus warranting an accelerated surveillance endoscopy and biopsy program every 6 months rather than every 1-3 years as indicated for non-dysplastic IM. Progression to high-grade dysplasia (HGD) indicates that the cells are even more "cancer-like", thus warranting an even higher frequency surveillance endoscopy and biopsy program (every 3 months). Many HGD patients may undergo photodynamic therapy (PDT) or surgical esophagectomy, rather than remain in a frequent surveillance program. This more aggressive therapy is warranted because of the high rate of progression of HGD to adenocarcinoma.
Esophageal adenocarcinoma most commonly occurs after an insidious progression from IM to LGD to HGD. Therefore, surveillance is increased upon diagnosis of worsening grades of dysplasia. The incidence of esophageal adenocarcinoma is rapidly increasing as middle-aged and elderly demographic sub-groups expand (Peters JH, Hagen JA, DeMeester SR. Barrett's Esophagus. J Gastrointest Surg 2004;8(1):1-17.) In 2004, the American Cancer Society reported that there were 14,250 new cases of esophageal cancer, and 13,300 deaths attributable to esophageal cancer (www.cancer.org). The U.S. National Cancer Institute Surveillance, Epidemiology and End Results Program reported that the increasing incidence of esophageal adenocarcinoma was greater than for any other cancer in the United States (www.cancer.gov).
Elimination of the diseased epithelium containing IM with dysplasia is an intuitively favorable step for patients with this diagnosis. In other disease states, such as colon polyps or premalignant skin lesions, removal of the premalignant tissue results in a reduction in the risk of ultimately developing cancer. This is a logical conclusion when considering the premalignant lesion of Barrett's esophagus (particularly Barrett's esophagus with dysplasia), as the "tissue at risk" can be completely removed by ablation. This premise has been tested in the Barrett's dysplasia population in photoablative trials using PDT for patients with HGD, where PDT imparted a 50% reduction in risk over controls for the development of adenocarcinoma (Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett's esophagus: follow-up. Gastrointest Endosc 1999;49(1):1-7.) The AIM Dysplasia Trial primary endpoints are removal of all dysplasia and IM, rather than detection of a difference in progression to adenocarcinoma or higher grades of dysplasia.
- Conditions
- Barrett Esophagus
- Being tested
- Ablation System plus anti-secretory medication, Sham procedure plus anti-secretory medication
- Keywords
- Barrett's Esophagus, Dysplasia, Radiofrequency Ablation
- Medical subject headings
- Barrett Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ablation System plus anti-secretory medicationDevice
Also called HALO 360, HALO 90
Treatment group subjects undergo up to 4 ablation procedures (circumferential or focal) plus standard anti-secretory drug therapy (proton pump inhibitor, PPI).
Sham procedure plus anti-secretory medicationDevice
The Sham Control group undergo an upper endoscopy procedure with sizing of the esophageal diameter (a component of the ablation procedure steps, deemed the sham procedure) plus standard anti-secretory drug therapy (Proton pump inhibitor, PPI)
| Study group | Role | What they receive |
|---|---|---|
| LGD Sham Procedure first then LGD Radiofrequency Ablation | Sham comparator | Sham procedure plus anti-secretory medication. Subjects with Low Grade Dysplasia (LGD) receive proton pump inhibitor (PPI) with dose of Esomeprazole 40 mg BID.
At 12 month, subjects crossover to receive radiofrequency ablation. Receives: Device: Sham procedure plus anti-secretory medication |
| LGD:Radiofrequency ablation | Active comparator | Ablation System plus anti-secretory medication. Subjects with Low Grade Dysplasia (LGD) undergo an upper endoscopy with sizing of the esophageal diameter followed by radiofrequency ablation plus standard anti-secretory therapy (proton pump inhibitor, PPI-dose: Esomeprazole 40 mg BID.) Receives: Device: Ablation System plus anti-secretory medication |
| HGD Sham Procedure first then HGD Radiofrequency Ablation | Sham comparator | Sham procedure plus anti-secretory medication. Subjects with High Grade Dysplasia (HGD) with proton pump inhibitor (PPI) dose: Esomeprazole 40 mg BID.
At 12 month, subjects crossover to receive radiofrequency ablation. Receives: Device: Sham procedure plus anti-secretory medication |
| HGD:Radiofrequency ablation | Active comparator | Ablation System plus anti-secretory medication. Subjects with High Grade Dysplasia (HGD) undergo an upper endoscopy with sizing of the esophageal diameter followed by radiofrequency ablation plus standard anti-secretory therapy (proton pump inhibitor, PPI-dose: Esomeprazole 40 mg BID.) Receives: Device: Ablation System plus anti-secretory medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
The % of Patients With Complete Eradication of Intestinal Metaplasia (IM) at 12 Month
% of patients with complete eradication of IM out of the number of participants analyzed at 12 month was calculated.
Measured: 12 month
The % of Patients With Complete Eradication of Dysplasia at 12 Month
% of patients with complete eradication of Dysplasia out of the number of participants analyzed at 12 month was calculated.
Measured: 12 month
The % of Patients With Complete Histological Clearance of Intestinal Metaplasia at 24 Months.
% of patients with complete eradication of IM out of the number of participants analyzed at 24 month was calculated.
Measured: 24 Month
5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Years
For patient who made it to the 5 year visit, % of patients demonstrating complete eradication of intestinal metaplasia (CE-IM) was calculated.
Measured: 5 years
Durability of Eradication With no Additional Treatments
Measured: 5 year
5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Years
For patient who made it to the 5 year visit, % of patients demonstrating complete eradication of dysplasia was calculated and all were free of dysplasia
Measured: 5 years
Secondary outcomes (16)
The % of Patients With Complete Histological Clearance of IM at 12 Months, Comparing Treatment Versus Sham Control Groups Within a Specific Dysplasia Subgroup
Measured: 12 months
Within the HGD Subgroup, the % of Patients With Complete Histological Clearance of HGD (CR-D) at 12 Months, Comparing Treatment Versus Sham Control Groups.
Measured: 12 Month
Histological Clearance of IM (% Biopsies)
% of patients with histological clearance of IM out of the number of participants analyzed at 12 month was calculated.
Measured: 12 months
Progression of Dysplasia (i.e., HGD to Adenocarcinoma, or LGD to HGD or Adenocarcinoma)
Measured: 5 year
Subject Discomfort : Chest Pain Score on Day 1
Chest pain score was measured on a visual analogue scale of 0 to 100, with higher scores indicating a greater severity of pain
Measured: Day 1 , if ablated
Quality of Life Questionnaire (Baseline v. 12 and 24 Mos)
Measured: 0, 12, and 24 months
Adverse Event Incidence
Data reported in the adverse event section
Measured: 12 months for Treatment and Sham Comparison
For 5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension and Available for Analysis at 5 Years Demonstrating Any Adenocarcinoma in Any Biopsy Obtained From the Esophageal Body Since Primary RFA (0-5 Years)
Measured: 5 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension and Available for Analysis at 5 Years Demonstrating Any Adenocarcinoma in Any Biopsy Obtained From the Esophageal Body After 2 Years and Inclusive of the 5 Year Visit
Measured: 5 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Year
Measured: 5 years
5 Year Extension:Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Year
Measured: 5 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 4 Year
Measured: 4 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 3 Year
Measured: 3 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-D at 4 Year
Measured: 4 years
5 Year Extension: Serious Adverse Event Incidence
Measured: 5 years
5 Year Extension: All Cause Mortality of the Group From 2 to 5 Years.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2006 (estimated)
- Study startFeb 2006
- Primary completionApr 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Barrett EsophagusStudies of the same condition, open and under way.
- More trials run by Medtronic - MITGThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medtronic - MITG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Nicholas J Shaheen, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00282672
- Sponsor's protocol ID
- B-204
- Status last verified
- Oct 2017
- First submitted
- 25 Jan 2006
- Last updated
- 6 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dunkin BJ, Martinez J, Bejarano PA, Smith CD, Chang K, Livingstone AS, Melvin WS. Thin-layer ablation of human esophageal epithelium using a bipolar radiofrequency balloon device. Surg Endosc. 2006 Jan;20(1):125-30. doi: 10.1007/s00464-005-8279-9. Epub 2005 Dec 7.
PubMed 16333533Ganz RA, Utley DS, Stern RA, Jackson J, Batts KP, Termin P. Complete ablation of esophageal epithelium with a balloon-based bipolar electrode: a phased evaluation in the porcine and in the human esophagus. Gastrointest Endosc. 2004 Dec;60(6):1002-10. doi: 10.1016/s0016-5107(04)02220-5.
PubMed 15605025Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009 May 28;360(22):2277-88. doi: 10.1056/NEJMoa0808145.
PubMed 19474425Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, Sharma VK, Eisen GM, Fennerty MB, Hunter JG, Bronner MP, Goldblum JR, Bennett AE, Mashimo H, Rothstein RI, Gordon SR, Edmundowicz SA, Madanick RD, Peery AF, Muthusamy VR, Chang KJ, Kimmey MB, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Dumot JA, Falk GW, Galanko JA, Jobe BA, Hawes RH, Hoffman BJ, Sharma P, Chak A, Lightdale CJ. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology. 2011 Aug;141(2):460-8. doi: 10.1053/j.gastro.2011.04.061. Epub 2011 May 6.
PubMed 21679712Shaheen NJ, Peery AF, Overholt BF, Lightdale CJ, Chak A, Wang KK, Hawes RH, Fleischer DE, Goldblum JR; AIM Dysplasia Investigators. Biopsy depth after radiofrequency ablation of dysplastic Barrett's esophagus. Gastrointest Endosc. 2010 Sep;72(3):490-496.e1. doi: 10.1016/j.gie.2010.04.010. Epub 2010 Jul 3.
PubMed 20598302
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ablation of Intestinal Metaplasia Containing Dysplasia (AIM Dysplasia Trial) A Multi-center, Randomized, Sham-Controlled Trial: Protocol Amendment to Extend Follow-up to 5 Years
- ClinicalTrials.gov ID
- NCT00282672
- Acronym / sponsor ID
- B-204
- Conditions
- Barrett Esophagus
- Keywords
- Barrett's Esophagus, Dysplasia, Radiofrequency Ablation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Medtronic - MITGIndustry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Study start
- Feb 2006
- Primary completion
- Apr 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 27 Jan 2006 (estimated)
- Results
- Posted 30 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if the intervention of a 510(k)-cleared endoscopically-guided (Halo Ablation systems), ablation system plus anti-secretory therapy is better than anti-secretory therapy alone in clearing Barrett's Esophagus.
Detailed description
Barrett's esophagus or intestinal metaplasia (IM) is a change in the epithelial lining of the esophagus. Barrett's esophagus develops as a result of chronic exposure of the esophagus to refluxed stomach acid and enzymes, as well as bile, resulting in recurrent mucosal injury. Injury is accompanied by inflammation and, ultimately, a cellular change (metaplasia) to a specialized columnar epithelium (Spechler SJ. Barrett's Esophagus. N Engl J Med 2002;346(11):836-842.)
Patients who have a diagnosis of Barrett's esophagus typically undergo surveillance endoscopy every 1-3 years with multiple biopsy specimens obtained to facilitate early detection of progression of IM to dysplasia (more severe precancerous changes) and adenocarcinoma. (Sampliner RE. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastro 2002;97:1888-1895.) Progression of IM to low-grade dysplasia (LGD) indicates that cells exhibit more "cancer-like" architecture, thus warranting an accelerated surveillance endoscopy and biopsy program every 6 months rather than every 1-3 years as indicated for non-dysplastic IM. Progression to high-grade dysplasia (HGD) indicates that the cells are even more "cancer-like", thus warranting an even higher frequency surveillance endoscopy and biopsy program (every 3 months). Many HGD patients may undergo photodynamic therapy (PDT) or surgical esophagectomy, rather than remain in a frequent surveillance program. This more aggressive therapy is warranted because of the high rate of progression of HGD to adenocarcinoma.
Esophageal adenocarcinoma most commonly occurs after an insidious progression from IM to LGD to HGD. Therefore, surveillance is increased upon diagnosis of worsening grades of dysplasia. The incidence of esophageal adenocarcinoma is rapidly increasing as middle-aged and elderly demographic sub-groups expand (Peters JH, Hagen JA, DeMeester SR. Barrett's Esophagus. J Gastrointest Surg 2004;8(1):1-17.) In 2004, the American Cancer Society reported that there were 14,250 new cases of esophageal cancer, and 13,300 deaths attributable to esophageal cancer (www.cancer.org). The U.S. National Cancer Institute Surveillance, Epidemiology and End Results Program reported that the increasing incidence of esophageal adenocarcinoma was greater than for any other cancer in the United States (www.cancer.gov).
Elimination of the diseased epithelium containing IM with dysplasia is an intuitively favorable step for patients with this diagnosis. In other disease states, such as colon polyps or premalignant skin lesions, removal of the premalignant tissue results in a reduction in the risk of ultimately developing cancer. This is a logical conclusion when considering the premalignant lesion of Barrett's esophagus (particularly Barrett's esophagus with dysplasia), as the "tissue at risk" can be completely removed by ablation. This premise has been tested in the Barrett's dysplasia population in photoablative trials using PDT for patients with HGD, where PDT imparted a 50% reduction in risk over controls for the development of adenocarcinoma (Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett's esophagus: follow-up. Gastrointest Endosc 1999;49(1):1-7.) The AIM Dysplasia Trial primary endpoints are removal of all dysplasia and IM, rather than detection of a difference in progression to adenocarcinoma or higher grades of dysplasia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LGD Sham Procedure first then LGD Radiofrequency Ablation | Sham comparator | Device: Sham procedure plus anti-secretory medicationSham procedure plus anti-secretory medication. Subjects with Low Grade Dysplasia (LGD) receive proton pump inhibitor (PPI) with dose of Esomeprazole 40 mg BID. At 12 month, subjects crossover to receive radiofrequency ablation. |
| LGD:Radiofrequency ablation | Active comparator | Device: Ablation System plus anti-secretory medicationAblation System plus anti-secretory medication. Subjects with Low Grade Dysplasia (LGD) undergo an upper endoscopy with sizing of the esophageal diameter followed by radiofrequency ablation plus standard anti-secretory therapy (proton pump inhibitor, PPI-dose: Esomeprazole 40 mg BID.) |
| HGD Sham Procedure first then HGD Radiofrequency Ablation | Sham comparator | Device: Sham procedure plus anti-secretory medicationSham procedure plus anti-secretory medication. Subjects with High Grade Dysplasia (HGD) with proton pump inhibitor (PPI) dose: Esomeprazole 40 mg BID. At 12 month, subjects crossover to receive radiofrequency ablation. |
| HGD:Radiofrequency ablation | Active comparator | Device: Ablation System plus anti-secretory medicationAblation System plus anti-secretory medication. Subjects with High Grade Dysplasia (HGD) undergo an upper endoscopy with sizing of the esophageal diameter followed by radiofrequency ablation plus standard anti-secretory therapy (proton pump inhibitor, PPI-dose: Esomeprazole 40 mg BID.) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ablation System plus anti-secretory medicationAlso: HALO 360, HALO 90Treatment group subjects undergo up to 4 ablation procedures (circumferential or focal) plus standard anti-secretory drug therapy (proton pump inhibitor, PPI). | Device | HGD:Radiofrequency ablation, LGD:Radiofrequency ablation |
| Sham procedure plus anti-secretory medicationThe Sham Control group undergo an upper endoscopy procedure with sizing of the esophageal diameter (a component of the ablation procedure steps, deemed the sham procedure) plus standard anti-secretory drug therapy (Proton pump inhibitor, PPI) | Device | HGD Sham Procedure first then HGD Radiofrequency Ablation, LGD Sham Procedure first then LGD Radiofrequency Ablation |
Primary outcome
The % of Patients With Complete Eradication of Intestinal Metaplasia (IM) at 12 Month
Time frame: 12 month
% of patients with complete eradication of IM out of the number of participants analyzed at 12 month was calculated.
The % of Patients With Complete Eradication of Dysplasia at 12 Month
Time frame: 12 month
% of patients with complete eradication of Dysplasia out of the number of participants analyzed at 12 month was calculated.
The % of Patients With Complete Histological Clearance of Intestinal Metaplasia at 24 Months.
Time frame: 24 Month
% of patients with complete eradication of IM out of the number of participants analyzed at 24 month was calculated.
5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Years
Time frame: 5 years
For patient who made it to the 5 year visit, % of patients demonstrating complete eradication of intestinal metaplasia (CE-IM) was calculated.
Durability of Eradication With no Additional Treatments
Time frame: 5 year
5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Years
Time frame: 5 years
For patient who made it to the 5 year visit, % of patients demonstrating complete eradication of dysplasia was calculated and all were free of dysplasia
16 secondary outcomes
The % of Patients With Complete Histological Clearance of IM at 12 Months, Comparing Treatment Versus Sham Control Groups Within a Specific Dysplasia Subgroup
Time frame: 12 months
Within the HGD Subgroup, the % of Patients With Complete Histological Clearance of HGD (CR-D) at 12 Months, Comparing Treatment Versus Sham Control Groups.
Time frame: 12 Month
Histological Clearance of IM (% Biopsies)
Time frame: 12 months
Progression of Dysplasia (i.e., HGD to Adenocarcinoma, or LGD to HGD or Adenocarcinoma)
Time frame: 5 year
Subject Discomfort : Chest Pain Score on Day 1
Time frame: Day 1 , if ablated
Quality of Life Questionnaire (Baseline v. 12 and 24 Mos)
Time frame: 0, 12, and 24 months
Adverse Event Incidence
Time frame: 12 months for Treatment and Sham Comparison
For 5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension and Available for Analysis at 5 Years Demonstrating Any Adenocarcinoma in Any Biopsy Obtained From the Esophageal Body Since Primary RFA (0-5 Years)
Time frame: 5 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension and Available for Analysis at 5 Years Demonstrating Any Adenocarcinoma in Any Biopsy Obtained From the Esophageal Body After 2 Years and Inclusive of the 5 Year Visit
Time frame: 5 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Year
Time frame: 5 years
5 Year Extension:Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Year
Time frame: 5 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 4 Year
Time frame: 4 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 3 Year
Time frame: 3 years
5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-D at 4 Year
Time frame: 4 years
5 Year Extension: Serious Adverse Event Incidence
Time frame: 5 years
5 Year Extension: All Cause Mortality of the Group From 2 to 5 Years.
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16333533Dunkin BJ, Martinez J, Bejarano PA, Smith CD, Chang K, Livingstone AS, Melvin WS. Thin-layer ablation of human esophageal epithelium using a bipolar radiofrequency balloon device. Surg Endosc. 2006 Jan;20(1):125-30. doi: 10.1007/s00464-005-8279-9. Epub 2005 Dec 7.
- Background: PubMed 15605025Ganz RA, Utley DS, Stern RA, Jackson J, Batts KP, Termin P. Complete ablation of esophageal epithelium with a balloon-based bipolar electrode: a phased evaluation in the porcine and in the human esophagus. Gastrointest Endosc. 2004 Dec;60(6):1002-10. doi: 10.1016/s0016-5107(04)02220-5.
- Results publication: PubMed 19474425Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009 May 28;360(22):2277-88. doi: 10.1056/NEJMoa0808145.
- Results publication: PubMed 21679712Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, Sharma VK, Eisen GM, Fennerty MB, Hunter JG, Bronner MP, Goldblum JR, Bennett AE, Mashimo H, Rothstein RI, Gordon SR, Edmundowicz SA, Madanick RD, Peery AF, Muthusamy VR, Chang KJ, Kimmey MB, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Dumot JA, Falk GW, Galanko JA, Jobe BA, Hawes RH, Hoffman BJ, Sharma P, Chak A, Lightdale CJ. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology. 2011 Aug;141(2):460-8. doi: 10.1053/j.gastro.2011.04.061. Epub 2011 May 6.
- Derived from this study: PubMed 20598302Shaheen NJ, Peery AF, Overholt BF, Lightdale CJ, Chak A, Wang KK, Hawes RH, Fleischer DE, Goldblum JR; AIM Dysplasia Investigators. Biopsy depth after radiofrequency ablation of dysplastic Barrett's esophagus. Gastrointest Endosc. 2010 Sep;72(3):490-496.e1. doi: 10.1016/j.gie.2010.04.010. Epub 2010 Jul 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas J Shaheen, MD principal investigator
University of North Carolina, Chapel Hill
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ablation System plus anti-secretory medication in people with Barrett Esophagus, run by Medtronic - MITG at 19 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The % of Patients With Complete Eradication of Intestinal Metaplasia (IM) at 12 Month (time frame: 12 month). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00282672, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.