Study Results
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View full resultsBasic Information
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COMPLETED
NA
127 participants
INTERVENTIONAL
2006-02-28
2014-08-31
Brief Summary
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Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
SINGLE
Study Groups
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LGD Sham Procedure first then LGD Radiofrequency Ablation
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.
Sham procedure plus anti-secretory medication
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)
LGD:Radiofrequency ablation
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.)
Ablation System plus anti-secretory medication
Treatment group subjects undergo up to 4 ablation procedures (circumferential or focal) plus standard anti-secretory drug therapy (proton pump inhibitor, PPI).
HGD Sham Procedure first then HGD Radiofrequency Ablation
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.
Sham procedure plus anti-secretory medication
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)
HGD:Radiofrequency ablation
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.)
Ablation System plus anti-secretory medication
Treatment group subjects undergo up to 4 ablation procedures (circumferential or focal) plus standard anti-secretory drug therapy (proton pump inhibitor, PPI).
Interventions
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Ablation System plus anti-secretory medication
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 medication
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)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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.
2. 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
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.
18 Years
80 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Medtronic - MITG
INDUSTRY
Responsible Party
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Principal Investigators
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Nicholas J Shaheen, MD
Role: PRINCIPAL_INVESTIGATOR
University of North Carolina, Chapel Hill
Locations
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Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
University of Arizona, VAMC
Tucson, Arizona, United States
UC Irvine Medical Center
Orange, California, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
Harvard, VA Boston Healthcare W Roxbury
West Roxbury, Massachusetts, United States
Mayo Clinic Rochester
Rochester, Minnesota, United States
University of Kansas School of Medicine - Veterans Affairs Medical Center
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Columbia University Medical Center
New York, New York, United States
UNC Center for Functional GI & Motility Disorders
Chapel Hill, North Carolina, United States
University Hospitals of Cleveland
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Oregon Health Sciences University
Portland, Oregon, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Gastrointestinal Associates
Knoxville, Tennessee, United States
VAMC Dallas
Dallas, Texas, United States
Tacoma Digestive Disease Research Center
Tacoma, Washington, United States
Countries
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References
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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.
Ganz 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.
Shaheen 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.
Shaheen 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.
Shaheen 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.
Other Identifiers
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B-204
Identifier Type: -
Identifier Source: org_study_id