Ablation of Intestinal Metaplasia Containing Dysplasia

NCT00282672 | Completed Results DMC

• 1 other identifier: B-204
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 19

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.

Conditions

Barrett Esophagus

Keywords

Barrett's Esophagus; Dysplasia; Radiofrequency Ablation

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  5 years

• Durability of Eradication With no Additional Treatments

  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

  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

  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.

  12 Month

• Histological Clearance of IM (% Biopsies)

  12 months

• Progression of Dysplasia (i.e., HGD to Adenocarcinoma, or LGD to HGD or Adenocarcinoma)

  5 year

• Subject Discomfort : Chest Pain Score on Day 1

  Day 1 , if ablated

Study Arms (4)

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.

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.)

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.

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.)

Device: Ablation System plus anti-secretory medication

Interventions

Ablation System plus anti-secretory medication DEVICE

Treatment group subjects undergo up to 4 ablation procedures (circumferential or focal) plus standard anti-secretory drug therapy (proton pump inhibitor, PPI).

Also known as: HALO 360, HALO 90

HGD:Radiofrequency ablation; LGD:Radiofrequency ablation

Sham procedure plus anti-secretory medication DEVICE

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 Sham Procedure first then HGD Radiofrequency Ablation; LGD Sham Procedure first then LGD Radiofrequency Ablation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• For female subjects of childbearing potential, a negative pregnancy test within 2 weeks of randomization.
• Subject eligible for treatment and follow-up endoscopy and biopsy as required by the Protocol.
• Subject willing to provide written, informed consent to participate in this clinical study and understands the responsibilities of trial participation.

You may not qualify if:

• Esophageal stricture preventing passage of endoscope or catheter. 3.Active esophagitis described as erosions or ulcerations encompassing more than 10% of distal esophagus.
• Any history of malignancy of the esophagus. 5.Prior radiation therapy to the esophagus,except head and neck region radiation therapy.
• Any previous ablative therapy within the esophagus (PDT, MPEC, APC, laser treatment, other).
• 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.
• Any previous esophageal surgery, including except fundoplication without complications (i.e. no slippage, dysphagia, etc).
• 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.
• 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.
• 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.
• The subject is currently enrolled in an investigational drug or device trial that clinically interferes with the AIM Dysplasia Trial endpoints.
• 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.

Sponsors & Collaborators

• Medtronic - MITG: lead
• AstraZeneca: collaborator

Study Sites (19)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of Arizona, VAMC

Tucson, Arizona, 85723, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Harvard, VA Boston Healthcare W Roxbury

West Roxbury, Massachusetts, 02132, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

University of Kansas School of Medicine - Veterans Affairs Medical Center

Kansas City, Missouri, 64128, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UNC Center for Functional GI & Motility Disorders

Chapel Hill, North Carolina, 27599, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Gastrointestinal Associates

Knoxville, Tennessee, 37909, United States

Location

VAMC Dallas

Dallas, Texas, 75216, United States

Location

Tacoma Digestive Disease Research Center

Tacoma, Washington, 98405, United States

Location

Related Publications (5)

• 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.

  PMID: 16333533 BACKGROUND

• 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.

  PMID: 15605025 BACKGROUND

• 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.

  PMID: 19474425 RESULT

• 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.

  PMID: 21679712 RESULT

• 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.

  PMID: 20598302 DERIVED

MeSH Terms

Conditions

Barrett Esophagus

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Results Point of Contact

• Title: Nicholas Shaheen
• Organization: University of north Carolina

nshaheen@med.unc.edu

(919) 966-7047

Study Officials

• Nicholas J Shaheen, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2006
• First Posted: January 27, 2006
• Study Start: February 1, 2006
• Primary Completion: April 1, 2014
• Study Completion: August 1, 2014
• Last Updated: November 6, 2017
• Results First Posted: December 30, 2015

Record last verified: 2017-10

Locations

US (19)