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Radiofrequency in the Treatment of Barrett's Oesophagus (HARMONI)

Primary Purpose

Esophageal Neoplasm

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Oesophagectomy
Radiofrequency ablation
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age over 18 years,
  • General Condition WHO 0, 1 or 2,
  • ASA Class I and II, eligible for endoscopic or surgical treatment with curative intent,
  • Histological diagnosis of high grade glandular epithelial neoplasia (Vienna 4-1 to 4-46), possibly multifocal or stage 0 (Tis, N0, M0),
  • Endoscopic and histological confirmed diagnosis of intestinal metaplasia,
  • Histological diagnosis confirmed by two endoscopies with biopsies and two pathological readings; biopsies should be carried out according to the protocol of the SFED (four-quadrant biopsies every cm) with at least once acetic acid for staining. Operators describe Barrett's esophagus using he SFED planimetric model. The final exam will be no more than two months before the date of treatment and should have been achieved in investigator establishment,

  • Extension height of Barrett's esophagus upstream of the upper part of the gastric folds or palisade vessels:

    • Minimum 1 cm,
    • Maximum 12 cm.

  • In case of previous treatment by mucosal resection or submucosal dissection (DSM) for severe dysplasia or microinvasive carcinoma:

    • the resected lesion must have been well differentiated and confined to the muscular mucosa (m3 maximum) on histological analysis,
    • resection should be more than two months,
    • resection must have been macroscopically complete laterally,
    • resection must have been histologically complete in depth,
    • resection must have been histologically complete laterally with regard to the microinvasive cancer, that is to say with a clear margin of safety (margin may be high-grade dysplasia provided that the latter has not macroscopic translation),
    • At least one endoscopic and histologic follow-up should be conducted with dye in a period of less than two months before the date of treatment, and at the investigator establishment.
  • Patient may take an inhibitor of proton pump equivalent to 2 times 40 mg of esomeprazole,
  • No mediastinal or celiac, or suspected metastatic lymph nodes by EUS,
  • Affiliation to a social security system or similar,
  • Lack of participation in another clinical study,
  • Informed consent signed.

Exclusion Criteria:

  • - Aged under 18,
  • Lack of informed consent signed,
  • Radiofrequency treatment history,
  • on going neoplastic history with a short prognosis,
  • Concomitant participation in another clinical study
  • Contraindication to general anesthesia,
  • Patient with an esophageal location of scleroderma
  • Presence of a cardiac pacemaker or stimulator
  • Pregnant women or likely to be in the absence of effective contraception,
  • Esophageal stenosis preventing the passage of an endoscope,
  • Histology other than glandular neoplasia,
  • History of or current history of esophageal cancer invading the submucosal layer of the esophagus or more,
  • Surgical treatment history (except anti-reflux treatment) or esophageal radiotherapy,
  • previous esophageal treatment by another method ablation: photodynamic therapy, argon plasma coagulation, laser, ....
  • Esophageal varices observed in endoscopy,
  • Coagulopathy or taking anticoagulants responsible an INR> 1.3 or a platelet count <75,000 per microL,
  • Life expectancy of less than 3 years, due to intercurrent disease, especially neoplastic,

  • Severe Medical pathology:

    • Liver cirrhosis (Child-Pugh all stages)
    • Respiratory failure:

VEMS (Maximum Expiratory Volume Second) <1L / min

PaO2 <60 mmHg

PaCO2> 45 mmHg

  • Renal failure (Cl Cr < 60 mL /min /1,73m²),
  • Heart attack within the last six months or progressive coronary artery disease,
  • Severe distal arteriopathie > stage II of Leriche and Fontaine

Sites / Locations

  • Hospices Civils de Lyon, Hépatogastroentérologie, Pavillon H, Hôpital Edouard Herriot

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Oesophagectomy

Radiofrequency ablation

Arm Description

While surgical reference technique for invasive cancer of the lower esophagus is the technique according to Lewis Santy, there is no consensus on the technique and surgical approaches lack of specific work in the particular case of superficial lesions . The centers will have the choice of using the technique according to Lewis Santy with gastric plasty or technique of esophagectomy without thoracotomy with lower mediastinal dissection. In the absence of consensus to date available, abdominal surgery time will be by laparotomy or laparoscopy (laparoscopic assisted technique called). In both cases, an exploratory laparoscopy for diagnostic purposes is realized to remove an extension of the disease that would indicate against-resection with curative intent. For surgery, patients will be put under antisecretory therapy proton-pump inhibitor; this at least throughout the duration of the study.

The equipment processing is: The radiofrequency generator, The radiofrequency balloon 360, the radiofrequency probe 90. The radiofrequency treatment should be carried out according to the following protocol: The radiofrequency treatment is done within 2 months following the last endoscopic assessment. The maximum number of sessions is 4, including 2 maximum with 360 Halo probe. Endoscopy is performed under general anesthesia. The removal must begin at the top 1cm above the upper pole of the lesion and must end 1cm below the lower pole of the lesion. The patient is left fasting until morning. In case of chest pain, the patient may receive analgesics. During the time of treatment, the patient must follow an antisecretory therapy pump inhibitor with dual proton dose orally. The patient should avoid taking aspirin or nonsteroidal anti-inflammatory drugs during the 10 days following each session.

Outcomes

Primary Outcome Measures

complete histological eradication of the high grade glandular epithelial neoplasia
The rate of success of the technique, success being defined as the complete histological eradication of the high grade glandular epithelial neoplasia without death attributable to the procedure. The relation of a death to the procedure will be determined by a committee of experts consisting of 3 surgeons or 3 hepatogastroenterologists depending on the arm, who do not participate to the study.

Secondary Outcome Measures

Rate of complete histological eradication of Barret's oesophagus
Rate of mortality all causes merged
Rate of mortality attributable to the procedure
Percentage of patients with severe adverse reaction and minor adverse reactions linked to the procedure used, described by anatomical site

Full Information

First Posted
September 23, 2015
Last Updated
March 23, 2022
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02558504
Brief Title
Radiofrequency in the Treatment of Barrett's Oesophagus
Acronym
HARMONI
Official Title
Clinical and Medico-economic Evaluation of Radiofrequency Ablation Versus Oesophagectomy in the Treatment of High Grade Dysplasia in Barrett's Oesophagus
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
January 7, 2013 (Actual)
Primary Completion Date
January 18, 2021 (Actual)
Study Completion Date
January 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
First intent treatment for superficial circular esophageal neoplasm is surgical resection. Endoscopic mucosal resection is not recommended due to the high rate of subsequent esophageal stenosis (higher than 80%). Surgical limits are related to a high level of morbidity due, in particular, to respiratory complications or infections that require prolonged hospitalisations, and by significant rate of mortality (from 2 to 5 %). As an alternative to the surgical treatment, an innovative technique to remove esophageal circular preneoplastic and neoplastic lesions has been developed: it consists to ablate the mucosa by means of a balloon of a fixed diameter which incorporates approximately 100 electrodes on its surface that emit radiofrequency waves (HALO® Radiofrequency Ablation Technology System). By varying the strength and the duration of the electrical impulses, it is possible to obtain a homogenous and controlled destruction of the tissue of the whole mucosa, leaving no remaining pre-neoplastic or neoplastic elements underneath. The technique will be used for high grade glandular epithelial neoplasia, Vienna 4-1 or 4-2, developed on a mucosa at risk, i.e. the Barrett's oesophagus, occupying more than half of the circumference of the esophagus and that requires surgical treatment. The expected benefit for the patient is linked to the reduced invasiveness of the technique in comparison to the surgery

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oesophagectomy
Arm Type
Active Comparator
Arm Description
While surgical reference technique for invasive cancer of the lower esophagus is the technique according to Lewis Santy, there is no consensus on the technique and surgical approaches lack of specific work in the particular case of superficial lesions . The centers will have the choice of using the technique according to Lewis Santy with gastric plasty or technique of esophagectomy without thoracotomy with lower mediastinal dissection. In the absence of consensus to date available, abdominal surgery time will be by laparotomy or laparoscopy (laparoscopic assisted technique called). In both cases, an exploratory laparoscopy for diagnostic purposes is realized to remove an extension of the disease that would indicate against-resection with curative intent. For surgery, patients will be put under antisecretory therapy proton-pump inhibitor; this at least throughout the duration of the study.
Arm Title
Radiofrequency ablation
Arm Type
Experimental
Arm Description
The equipment processing is: The radiofrequency generator, The radiofrequency balloon 360, the radiofrequency probe 90. The radiofrequency treatment should be carried out according to the following protocol: The radiofrequency treatment is done within 2 months following the last endoscopic assessment. The maximum number of sessions is 4, including 2 maximum with 360 Halo probe. Endoscopy is performed under general anesthesia. The removal must begin at the top 1cm above the upper pole of the lesion and must end 1cm below the lower pole of the lesion. The patient is left fasting until morning. In case of chest pain, the patient may receive analgesics. During the time of treatment, the patient must follow an antisecretory therapy pump inhibitor with dual proton dose orally. The patient should avoid taking aspirin or nonsteroidal anti-inflammatory drugs during the 10 days following each session.
Intervention Type
Procedure
Intervention Name(s)
Oesophagectomy
Intervention Type
Device
Intervention Name(s)
Radiofrequency ablation
Other Intervention Name(s)
esophageal radiofrequency
Primary Outcome Measure Information:
Title
complete histological eradication of the high grade glandular epithelial neoplasia
Description
The rate of success of the technique, success being defined as the complete histological eradication of the high grade glandular epithelial neoplasia without death attributable to the procedure. The relation of a death to the procedure will be determined by a committee of experts consisting of 3 surgeons or 3 hepatogastroenterologists depending on the arm, who do not participate to the study.
Time Frame
12 months after the end of treatment
Secondary Outcome Measure Information:
Title
Rate of complete histological eradication of Barret's oesophagus
Time Frame
12 months after the end of treatment
Title
Rate of mortality all causes merged
Time Frame
12 months after the end of treatment
Title
Rate of mortality attributable to the procedure
Time Frame
30 days after end of the treatment
Title
Percentage of patients with severe adverse reaction and minor adverse reactions linked to the procedure used, described by anatomical site
Time Frame
30 days and 12 months after end of the treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age over 18 years, General Condition WHO 0, 1 or 2, ASA Class I and II, eligible for endoscopic or surgical treatment with curative intent, Histological diagnosis of high grade glandular epithelial neoplasia (Vienna 4-1 to 4-46), possibly multifocal or stage 0 (Tis, N0, M0), Endoscopic and histological confirmed diagnosis of intestinal metaplasia, Histological diagnosis confirmed by two endoscopies with biopsies and two pathological readings; biopsies should be carried out according to the protocol of the SFED (four-quadrant biopsies every cm) with at least once acetic acid for staining. Operators describe Barrett's esophagus using he SFED planimetric model. The final exam will be no more than two months before the date of treatment and should have been achieved in investigator establishment, Extension height of Barrett's esophagus upstream of the upper part of the gastric folds or palisade vessels: Minimum 1 cm, Maximum 12 cm. In case of previous treatment by mucosal resection or submucosal dissection (DSM) for severe dysplasia or microinvasive carcinoma: the resected lesion must have been well differentiated and confined to the muscular mucosa (m3 maximum) on histological analysis, resection should be more than two months, resection must have been macroscopically complete laterally, resection must have been histologically complete in depth, resection must have been histologically complete laterally with regard to the microinvasive cancer, that is to say with a clear margin of safety (margin may be high-grade dysplasia provided that the latter has not macroscopic translation), At least one endoscopic and histologic follow-up should be conducted with dye in a period of less than two months before the date of treatment, and at the investigator establishment. Patient may take an inhibitor of proton pump equivalent to 2 times 40 mg of esomeprazole, No mediastinal or celiac, or suspected metastatic lymph nodes by EUS, Affiliation to a social security system or similar, Lack of participation in another clinical study, Informed consent signed. Exclusion Criteria: - Aged under 18, Lack of informed consent signed, Radiofrequency treatment history, on going neoplastic history with a short prognosis, Concomitant participation in another clinical study Contraindication to general anesthesia, Patient with an esophageal location of scleroderma Presence of a cardiac pacemaker or stimulator Pregnant women or likely to be in the absence of effective contraception, Esophageal stenosis preventing the passage of an endoscope, Histology other than glandular neoplasia, History of or current history of esophageal cancer invading the submucosal layer of the esophagus or more, Surgical treatment history (except anti-reflux treatment) or esophageal radiotherapy, previous esophageal treatment by another method ablation: photodynamic therapy, argon plasma coagulation, laser, .... Esophageal varices observed in endoscopy, Coagulopathy or taking anticoagulants responsible an INR> 1.3 or a platelet count <75,000 per microL, Life expectancy of less than 3 years, due to intercurrent disease, especially neoplastic, Severe Medical pathology: Liver cirrhosis (Child-Pugh all stages) Respiratory failure: VEMS (Maximum Expiratory Volume Second) <1L / min PaO2 <60 mmHg PaCO2> 45 mmHg Renal failure (Cl Cr < 60 mL /min /1,73m²), Heart attack within the last six months or progressive coronary artery disease, Severe distal arteriopathie > stage II of Leriche and Fontaine
Facility Information:
Facility Name
Hospices Civils de Lyon, Hépatogastroentérologie, Pavillon H, Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France

12. IPD Sharing Statement

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Radiofrequency in the Treatment of Barrett's Oesophagus

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