Ablation of Intestinal Metaplasia Containing Dysplasia

• Sponsor: Medtronic - MITG (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00282672
• Collaborator: AstraZeneca (Industry)
• Enrollment: 127
• Locations: 19
• Arms: 4
• Duration (Months): 101.9
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Barrett Esophagus	Device: Ablation System plus anti-secretory medication; Device: Sham procedure plus anti-secretory medication	N/A

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

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: 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.	Device: 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)
Active Comparator: 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.)	Device: 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).; Other Names: HALO 360 HALO 90
Sham Comparator: 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.	Device: 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)
Active Comparator: 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.)	Device: 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).; Other Names: HALO 360 HALO 90

Outcome Measures

Primary Outcome Measures

1. The % of Patients With Complete Eradication of Intestinal Metaplasia (IM) at 12 Month [12 month]

   % of patients with complete eradication of IM out of the number of participants analyzed at 12 month was calculated.

2. The % of Patients With Complete Eradication of Dysplasia at 12 Month [12 month]

   % of patients with complete eradication of Dysplasia out of the number of participants analyzed at 12 month was calculated.

3. The % of Patients With Complete Histological Clearance of Intestinal Metaplasia at 24 Months. [24 Month]

   % of patients with complete eradication of IM out of the number of participants analyzed at 24 month was calculated.

4. 5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Years [5 years]

   For patient who made it to the 5 year visit, % of patients demonstrating complete eradication of intestinal metaplasia (CE-IM) was calculated.

5. Durability of Eradication With no Additional Treatments [5 year]

6. 5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Years [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

Secondary Outcome Measures

1. The % of Patients With Complete Histological Clearance of IM at 12 Months, Comparing Treatment Versus Sham Control Groups Within a Specific Dysplasia Subgroup [12 months]

2. Within the HGD Subgroup, the % of Patients With Complete Histological Clearance of HGD (CR-D) at 12 Months, Comparing Treatment Versus Sham Control Groups. [12 Month]

3. Histological Clearance of IM (% Biopsies) [12 months]

   % of patients with histological clearance of IM out of the number of participants analyzed at 12 month was calculated.

4. Progression of Dysplasia (i.e., HGD to Adenocarcinoma, or LGD to HGD or Adenocarcinoma) [5 year]

5. Subject Discomfort : Chest Pain Score on Day 1 [Day 1 , if ablated]

   Chest pain score was measured on a visual analogue scale of 0 to 100, with higher scores indicating a greater severity of pain

6. Quality of Life Questionnaire (Baseline v. 12 and 24 Mos) [0, 12, and 24 months]

7. Adverse Event Incidence [12 months for Treatment and Sham Comparison]

   Data reported in the adverse event section

8. 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) [5 years]

9. 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 [5 years]

10. 5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Year [5 years]

11. 5 Year Extension:Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Year [5 years]

12. 5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 4 Year [4 years]

13. 5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-IM at 3 Year [3 years]

14. 5 Year Extension: Proportion (%) of All Patients Enrolled in This Extension Protocol and Available for Analysis Demonstrating CR-D at 4 Year [4 years]

15. 5 Year Extension: Serious Adverse Event Incidence [5 years]

16. 5 Year Extension: All Cause Mortality of the Group From 2 to 5 Years. [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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.

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
2	University of Arizona, VAMC	Tucson	Arizona	United States	85723
3	UC Irvine Medical Center	Orange	California	United States	92868
4	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
5	Harvard, VA Boston Healthcare W Roxbury	West Roxbury	Massachusetts	United States	02132
6	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
7	University of Kansas School of Medicine - Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
10	Columbia University Medical Center	New York	New York	United States	10032
11	UNC Center for Functional GI & Motility Disorders	Chapel Hill	North Carolina	United States	27599
12	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
13	Cleveland Clinic	Cleveland	Ohio	United States	44195
14	Oregon Health Sciences University	Portland	Oregon	United States	97239
15	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	Gastrointestinal Associates	Knoxville	Tennessee	United States	37909
18	VAMC Dallas	Dallas	Texas	United States	75216
19	Tacoma Digestive Disease Research Center	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Medtronic - MITG
• AstraZeneca

Investigators

• Principal Investigator: Nicholas J Shaheen, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

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. 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.

• Responsible Party: Medtronic - MITG
• ClinicalTrials.gov Identifier: NCT00282672
• Other Study ID Numbers: B-204
• First Posted: Jan 27, 2006
• Last Update Posted: Nov 6, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Medtronic - MITG: Barrett's Esophagus; Dysplasia; Radiofrequency Ablation
• Additional relevant MeSH terms: Barrett Esophagus; Metaplasia

Study Results

Participant Flow

Arm/Group Title	LGD Sham Procedure First Then LGD Radiofrequency Ablation	LGD Radiofrequency Ablation	HGD Sham Procedure First Then HGD Radiofrequency Ablation	HGD Radiofrequency Ablation
Arm/Group Description	After the 1 year follow up was completed, all sham patients were offered cross-over to receive RFA.	After the 1 year follow up was completed, all sham patients were offered cross-over to receive RFA.
Period Title: 1 Year
STARTED	22	42	21	42
COMPLETED	19	40	20	38
NOT COMPLETED	3	2	1	4
Period Title: 1 Year
STARTED	19	40	16	38
COMPLETED	16	39	15	36
NOT COMPLETED	3	1	1	2
Period Title: 1 Year
STARTED	15	32	12	25
COMPLETED	14	27	12	20
NOT COMPLETED	1	5	0	5

Baseline Characteristics

Arm/Group Title	LGD Sham Procedure First Then LGD Radiofrequency Ablation	LGD Radiofrequency Ablation	HGD Sham Procedure First Then LGD Radiofrequency Ablation	HGD Radiofrequency Ablation	Total
Arm/Group Description	After the 1 year follow up was completed, all sham patients were offered cross-over to receive RFA.	After the 1 year follow up was completed, all sham patients were offered cross-over to receive RFA.	Total of all reporting groups
Overall Participants	22	42	21	42	127
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (1.9)	66.3 (1.4)	67.3 (1.8)	65.9 (1.4)	65.95 (8.95)
Sex: Female, Male (Count of Participants)
Female	3 13.6%	9 21.4%	0 0%	5 11.9%	17 13.4%
Male	19 86.4%	33 78.6%	21 100%	37 88.1%	110 86.6%
Region of Enrollment (participants) [Number]
United States	22 100%	42 100%	21 100%	42 100%	127 100%

Outcome Measures

1. Primary Outcome

Title	The % of Patients With Complete Eradication of Intestinal Metaplasia (IM) at 12 Month
Description	% of patients with complete eradication of IM out of the number of participants analyzed at 12 month was calculated.
Time Frame	12 month

Outcome Measure Data

Analysis Population Description

LGD: Radiofrequency group- 2 patients withdrew and were not analyzed, HGD: Radiofrequency Ablation: 4 patients withdrew and were not analyzed. LGD Sham procedure first then LGD Radiofrequency Ablation group and HGD Sham procedure first then HGD Radiofrequency Ablation group were not analyzed to measure the CR-IM at one year.

Arm/Group Title	LGD:Radiofrequency Ablation	HGD:Radiofrequency Ablation
Arm/Group Description
Measure Participants	40	38
Number [percentage of participants]	85 386.4%	81.5 194%

2. Primary Outcome

Title	The % of Patients With Complete Eradication of Dysplasia at 12 Month
Description	% of patients with complete eradication of Dysplasia out of the number of participants analyzed at 12 month was calculated.
Time Frame	12 month

Outcome Measure Data

Analysis Population Description

LGD: Radiofrequency group- 2 patients withdrew and were not analyzed, HGD: Radiofrequency Ablation: 4 patients withdrew and were not analyzed. LGD Sham procedure first then LGD Radiofrequency Ablation group and HGD Sham procedure first then HGD Radiofrequency Ablation group were not analyzed to measure the CR-D at one year.

Arm/Group Title	LGD:Radiofrequency	HGD:Radiofrequency
Arm/Group Description
Measure Participants	40	38
Number [percentage of participants]	95 431.8%	89.5 213.1%

3. Primary Outcome

Title	The % of Patients With Complete Histological Clearance of Intestinal Metaplasia at 24 Months.
Description	% of patients with complete eradication of IM out of the number of participants analyzed at 24 month was calculated.
Time Frame	24 Month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LGD Sham Procedure First Then LGD Radiofrequency Ablation	LGD:Radiofrequency	HGD Sham Procedure First Then HGD Radiofrequency Ablation	HGD Radiofrequency Ablation
Arm/Group Description	Crossed over to LGD:Radiofrequency	Crossed over to HGD: Radiofrequency
Measure Participants	16	39	15	36
Number [percentage of participants]	100 454.5%	97.4 231.9%	93.3 444.3%	88.9 211.7%

4. Primary Outcome

Title	5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-IM at 5 Years
Description	For patient who made it to the 5 year visit, % of patients demonstrating complete eradication of intestinal metaplasia (CE-IM) was calculated.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

patient who made it to the 5 year visit

Arm/Group Title	All LGD Patients	All HGD Patients
Arm/Group Description	LGD: Sham procedure group crossed over to LGD: Radiofrequency group at 12 month	HGD: Sham procedure group crossed over to HGD: Radiofrequency group at 12 month
Measure Participants	41	32
Number [percentage of participants]	85.3 387.7%	96.8 230.5%

5. Primary Outcome

Title	Durability of Eradication With no Additional Treatments
Time Frame	5 year

Outcome Measure Data

Analysis Population Description

41 LGD subjects and 32 HGD subjects completed 5 year visit

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	73
Number [percentage of participants]	75 340.9%

6. Primary Outcome

Title	5 Year Extension: % of All Patients Enrolled in the Extension Protocol and Available for Analysis Demonstrating CR-D at 5 Years
Description	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
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All LGD Patients	All HGD Patients
Arm/Group Description
Measure Participants	41	32
Number [percentage of participants]	100 454.5%	96.8 230.5%

7. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LGD Radiofrequency Ablation	LGD Sham Procedure First Then LGD Radiofrequency Ablation	HGD Radiofrequency Ablation	HGD Sham Procedure First Then HGD Radiofrequency Ablation
Arm/Group Description
Measure Participants	40	18	38	15
Number [percentage of participants]	85 386.4%	72.2 171.9%	81.5 388.1%	80 190.5%

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

16 HGD Sham procedure subjects crossed over to RFA treatment after one year

Arm/Group Title	HGD Radiofrequency Ablation	HGD Sham Procedure First Then HGD Radiofrequency Ablation
Arm/Group Description
Measure Participants	38	15
Number [percentage of participants]	89.4 406.4%	86.6 206.2%

9. Secondary Outcome

Title	Histological Clearance of IM (% Biopsies)
Description	% of patients with histological clearance of IM out of the number of participants analyzed at 12 month was calculated.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LGD Radiofrequency Ablation	LGD Sham Procedure First Then LGD Radiofrequency Ablation	HGD Radiofrequency Ablation	HGD Sham Procedure First Then HGD Radiofrequency Ablation
Arm/Group Description
Measure Participants	40	18	38	15
Number [percentage of participants]	85 386.4%	72.2 171.9%	81.5 388.1%	80 190.5%

10. Secondary Outcome

Title	Progression of Dysplasia (i.e., HGD to Adenocarcinoma, or LGD to HGD or Adenocarcinoma)
Time Frame	5 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LGD to HGD	LGD to IMC	HGD to IMC
Arm/Group Description
Measure Participants	47	47	37
Number [participants]	5 22.7%	1 2.4%	1 4.8%

11. Secondary Outcome

Title	Subject Discomfort : Chest Pain Score on Day 1
Description	Chest pain score was measured on a visual analogue scale of 0 to 100, with higher scores indicating a greater severity of pain
Time Frame	Day 1 , if ablated

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LGD Sham Procedure First Then LGD Radiofrequency Ablation	LGD Radiofrequency Ablation	HGD Sham Procedure First Then HGD Radiofrequency Ablation	HGD Radiofrequency Ablation
Arm/Group Description
Measure Participants	20	40	20	41
Median (Inter-Quartile Range) [Scores on a scale]	0	26	0	22

12. Secondary Outcome

Title	Quality of Life Questionnaire (Baseline v. 12 and 24 Mos)
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

Data had not been collected consistently to analyze the data.

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	0

13. Secondary Outcome

Title	Adverse Event Incidence
Description	Data reported in the adverse event section
Time Frame	12 months for Treatment and Sham Comparison

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham Patients	Treatment Patients
Arm/Group Description	Patients randomized to Sham Procedure arm.	Patients randomized to Radiofrequency Ablation at start of study and underwent RFA treatment at randomization.
Measure Participants	43	84
AE's related to procedure	7	32
AE's unrelated to procedure	17	34

14. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

41 LGD patients and 21 HGD subjects completed the 5 year study and used for analysis.

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	73
Number [percentage of participants]	2.7 12.3%

15. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Similar analysis was performed and the result is provided for the outcome measure #14. The data were collected to answer the outcome measure #14.

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	0

16. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	41
Number [percentage of participants]	85.4 388.2%

17. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	41
Number [percentage of participants]	100 454.5%

18. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	43
Number [percentage of participants]	79.1 359.5%

19. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	42
Number [percentage of participants]	92.9 422.3%

20. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	43
Number [percentage of participants]	93 422.7%

21. Secondary Outcome

Title	5 Year Extension: Serious Adverse Event Incidence
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description
Measure Participants	127
Bleed	1 4.5%
Chest Pain	3 13.6%

22. Secondary Outcome

Title	5 Year Extension: All Cause Mortality of the Group From 2 to 5 Years.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Groups
Arm/Group Description
Measure Participants	127
Number [percentage of participants]	0 0%

Adverse Events

Arm/Group Title	LGD Sham Procedure First Then LGD Radiofrequency Ablation		LGD Radiofrequency Ablation		HGD Sham Procedure First Then HGD Radiofrequency Ablation		HGD Radiofrequency Ablation
Arm/Group Description
All Cause Mortality
	LGD Sham Procedure First Then LGD Radiofrequency Ablation		LGD Radiofrequency Ablation		HGD Sham Procedure First Then HGD Radiofrequency Ablation		HGD Radiofrequency Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LGD Sham Procedure First Then LGD Radiofrequency Ablation		LGD Radiofrequency Ablation		HGD Sham Procedure First Then HGD Radiofrequency Ablation		HGD Radiofrequency Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		1/42 (2.4%)		0/21 (0%)		2/42 (4.8%)
Injury, poisoning and procedural complications
PAIN, NAUSEA, VOMITTING, FULLNESS, ABDOMINAL DISCOMFORT	1/22 (4.5%)	1	0/42 (0%)	0	0/21 (0%)	0	2/42 (4.8%)	2
Upper GI Bleed	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	LGD Sham Procedure First Then LGD Radiofrequency Ablation		LGD Radiofrequency Ablation		HGD Sham Procedure First Then HGD Radiofrequency Ablation		HGD Radiofrequency Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/22 (18.2%)		11/42 (26.2%)		7/21 (33.3%)		12/42 (28.6%)
Injury, poisoning and procedural complications
MUCOSAL INJURY	1/22 (4.5%)	1	0/42 (0%)	0	0/21 (0%)	0	2/42 (4.8%)	2
MELENA	0/22 (0%)	0	0/42 (0%)	0	0/21 (0%)	0	1/42 (2.4%)	1
STRICTURE REQUIRING DILATATION	2/22 (9.1%)	3	1/42 (2.4%)	1	2/21 (9.5%)	3	4/42 (9.5%)	4
VOMITTING	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	2/42 (4.8%)	2
CHEST PAIN/ THROAT PAIN / NAUSEA	0/22 (0%)	0	1/42 (2.4%)	1	1/21 (4.8%)	1	1/42 (2.4%)	1
STRICTURE / SCARRING	2/22 (9.1%)	2	1/42 (2.4%)	1	1/21 (4.8%)	1	1/42 (2.4%)	1
BLOATED, REFLUX SENSATION, DIFFICULTY SWALLOWING	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
NARROWED ESOPHAGUS	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
ESOPHAGEAL VARICES	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
FEVER; DIARRHEA	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
PAINFUL SWALLOWING / CHEST PAIN	0/22 (0%)	0	1/42 (2.4%)	1	1/21 (4.8%)	1	1/42 (2.4%)	1
PREMATURE FULLNESS WITH MEALS	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
PAINFUL SWALLOWING, ABDOMINAL PAIN, CHEST PAIN.	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
FEVER, LARYNGITIS, PHARYNGITIS AND BRONCHITIS	0/22 (0%)	0	1/42 (2.4%)	1	0/21 (0%)	0	0/42 (0%)	0
SEVERE NAUSEA,VOMITING, ULCERATION, WEIGHT LOSS	0/22 (0%)	0	0/42 (0%)	0	1/21 (4.8%)	1	0/42 (0%)	0
ULCERATION	0/22 (0%)	0	0/42 (0%)	0	1/21 (4.8%)	1	0/42 (0%)	0
DYSPHAGIA	0/22 (0%)	0	0/42 (0%)	0	1/21 (4.8%)	1	1/42 (2.4%)	1
EROSIVE ESOPHAGEAL MUCOSA	0/22 (0%)	0	0/42 (0%)	0	1/21 (4.8%)	1	0/42 (0%)	0
RIGHT EAR ACHE	0/22 (0%)	0	0/42 (0%)	0	1/21 (4.8%)	1	0/42 (0%)	0
ABDOMINAL PAIN	0/22 (0%)	0	0/42 (0%)	0	0/21 (0%)	0	2/42 (4.8%)	3
PAIN; ELEVATED BP	0/22 (0%)	0	0/42 (0%)	0	0/21 (0%)	0	1/42 (2.4%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.