Outcomes of Esophageal Self Dilation for Benign Refractory Esophageal Stricture Management: Randomized Controlled Trial
Phase: NA
Conditions: Esophageal Dilation, Refractory Benign Esophageal Stricture
Sponsor: Mayo Clinic

 
 
Outcomes of Esophageal Self Dilation for 
Benign Refractory Esophageal Stricture 
Management: Randomized Controlled Trial 
 
NCT03738566 
 
November 19, 2021 

Version 5 
Date: 3/14/2019 5/6/2019 11/19/2021 
 
Title: Outcomes of Esophageal Self Dilation for Benign Refractory Esophageal Stricture 
Management: Randomized Controlled Trial  
 
Principal Investigator: Jeffrey Alexander, MD 
Co-Principal Investigator: Dr Francisco Ramirez 
Co- Investigators: David A Katzka MD, Tarek Sawas, MD Yi Qin, MD, Allon Kahn, Mike, 
Michael Crowell 
 
Study Coordinators: Crystal Lavey, CCRP, Alyssa Johnson, CRC 
 
Background: 
 
Benign esophageal strictures can be challenging condition to treat. The mainstay of 
treatment is endoscopic dilations. However, 30 to 40% of these strictures recur despite rigorous 
dilations1. Although a consensus definition does not exist, a stricture is typically termed as a 
refractory benign esophageal stricture (RBES), when there is a failure to maintain luminal 
patency after at least 5 endoscopic dilations 2. These strictures are fibrotic and cicatricle, and are 
most commonly the sequelae of radiation, surgery, caustic agent ingestion, peptic injury, 
photodynamic therapy, or endoscopic mucosal resection3. Hypertrophy of scar tissue is the 
underlying mechanism leading to re-stenosis4.  
Patients with RBES are extremely difficult to manage and the current armamentarium 
includes repeated endoscopic dilations, corticosteroid or mitomycin C injections, incisional 
therapy, and/ or temporary stent placement5-10. These procedures are costly, their efficacy can be 
short-lived, and are associated with great burden both for the patient and clinician. Despite 
intensive interventions, patients often still fail and go on to require enteral nutrition support. The 
largest study on the natural history of RBES found that the mean dysphagia free interval was 3 
months, and only 2.4 months for patients treated with endoscopic stenting. The clinical success 
rate for patients treated with stenting was only 12.5%.11   
Esophageal self -dilation therapy (ESDT), where the patient learns to pass a polyvinyl 
dilator orally on a routine basis, has been in practice since at least the 1970s, however, no 
prospective studies have evaluated the outcomes ESDT. The largest study to date on ESDT 
retrospectively studied 30 patients12, and all the published studies on this topic consists of less 
than 50 patients in total12-19. In these retrospective and observational studies, ESDT appears to be 
effective for RBES, reducing the number of endoscopic dilations from an average of 21.7 to an 
average of 112. However, many questions with regards to ESDT remain unanswered. Firstly, in 
the absence of any prospective data it is uncertain how effective ESDT is. Moreover, currently 
patients are offered ESDT when standard therapies fail.  
 
Hypotheses: 
 
Among patients with refractory benign esophageal stricture who were treated endoscopically, we 
hypothesized the following: 

1. Compared to an endoscopy as needed approach, esophageal self -dilation therapy decreases 
the number of endoscopic dilations and prolongs dysphagia free intervals 
2. Esophageal self -dilation therapy is a safe and well tolerated therapy  
3. ESDT significantly lowers health cost in managing refractory esophageal stricture 
 
Primary Aims: 
 
1. Assess the clinical efficacy of ESDT for patients with RBES defined as number of 
endoscopic interventions  6 months following serial dilation 
 
Secondary Aims: 
1. Length of intervention free interval and dysphagia score  
2. Evaluate factors which could influence clinical success of ESDT including etiology and 
location of the stricture  
3. Assess the safety of ESDT by identifying clinically significant adverse events including 
perforation, bleeding and pain.  
4. Assess acceptance of ESDT by measuring the number of patients who accepts the 
procedure and are able to complete it over the total number of patients offered ESDT 
5. The cost saving in ESDT compared to the current standard of care (repetitive endoscopic 
dilation) 
6. Evaluate long term outcomes of self-dilatation at 3, 6, 9 and 12 months following 
participation in the 6 month randomized or prospective observational trial 
 
 
Methods: 
Study Design: 
 
This is a prospective randomized controlled trial evaluating the outcomes of self-dilation. 
Patients who present to the esophageal clinic in Rochester MN and Mayo Clinic Phoenix, AZ 
with refractory benign esophageal strictures who undergo standard clinical care of serial 
endoscopic dilation to achieve an esophageal diameter of at least 10-12 mm will be randomized 
to either continuing standard clinical care consisting of endoscopic dilation as needed vs self-
dilation therapy.  
 
Inclusion Criteria for Patients: 
1. 18 years of age or older  
2. Refractory benign esophageal stricture defined as an esophageal stricture with persistent 
dysphagia despite undergoing 5 endoscopic dilations within a 1 year period. Persistent 
dysphagia will be considered if patients has solid food dysphagia at least once a week  
 
Exclusion Criteria  
1. Patient with malignant esophageal stricture  
2. Angulated stricture which prevents safe passage of Maloney dilator in office setting 
3. In ability to achieve an esophageal diameter of 10 mm with endosocpic dilatiation 
4. Known significant esophageal motor disorder (i.e. achalasia, aperistalsis, functional 
obstruction, jackhammer, distal esophageal spasm)* 

5. The presence of esophageal stent 
6. Inability to learn self-dilation secondary to blindness or cognitive dysfunction 
7. Use of chronic anticoagulants  
 
Study Flow and Recruitment 
  
1. Patients referred to the esophageal clinic with dysphagia secondary to RBES will be asked to 
complete the Mayo Dysphagia Questionnaire (MDQ-30). The MDQ will be completed 
before obtaining informed consent. Quality of life will also be measured at the beginning at 
end of the 6 months using Short form-36 
2. First, patients will undergo the standard of care which is serial endoscopic therapy with 
esophageal dilation. Patients will be dilated 1-3 times a week with the aim to achieve a post-
dilation luminal diameter of at least 10-12 mm 
3. After informed consent, participants will be randomized to one of two groups using a block 
randomization approach; Group 1) self-dilation, group 2) observation with repeat endoscopy 
and dilations as needed at symptoms recurrence.  
4. Patients randomized to self-dilation who refuse self-dilation will be assigned to the 
observation group and will be counted in the ESDT failure   
5. Patients randomized to ESDT will be taught ESDT immediately following the last 
endoscopic dilation. ESDT teaching will take over 1-3 training sessions by one of two 
esophageal physicians and a nurse. Patients will be instructed to start ESDT twice a day. If 
dysphagia is adequately controlled, and there was no resistance with passing the dilator, 
patients will be asked to decrease the frequency of ESDT to daily, weekly, and monthly over 
an average period of 6 months as directed by the esophageal care team.   
6. Patients randomized to the observation group will undergo repeat endoscopy and dilation as 
needed if their dysphagia relapse which is the current standard of care. A relapse will be 
considered if a patient developed solid food dysphagia at least once a week. 
7. Patients in the observation group who requires 2 endoscopic dilation within 3 months will be 
offered to cross over to the self dilation group  
8. Patients in the self dilation group who can not tolerate self dilation but require more 
treatment will be offered to crossover to the standard clinical care grouph endoscopic dilation 
as needed after 3 months from the entry point 
9. At the end of the six months, the standard clinical care group will be offered self-dilation.  
10. At any point of the study if patients decide to crossover to the other group, this will be 
allowed but counted as treatment failure 
11. Close supervision and follow up will be performed via weekly phone calls from a member of 
the study personnellPatients will be asked to complete the MDQ-30 monthly and at the end 
of the study.  
12. Patients who decline participation in the randomized study will be offered both treatments 
clinically then will be followed prospectively and their data will be collected. These patients 
will be asked to fill the dysphagia score to assess symptoms regardless of the method of 
treatment. 
13. At the conclusion of the 6 months randomized or observational study duration patients will 
be offered the following: 
1. All patients who participated in the randomized or observational study will be offered 
to continue prospective follow up with phone calls to obtain the MDQ-30 score and 

need for endoscopy at 3, 6, 9, and 12 months after conclusion of the initial 6 month 
duration of the study 
 
Remuneration:  
1. Patients in the randomized self-dilation group will be provided with the self-dilator free of 
charge.  
2. Patients in the randomized observation group will receive endoscopic dilation as needed with 
charges to the patients and their health insurance as appropriate since this is the standard of 
care 
3. Patients in both groups will receive stipend of $25 for each questionnaire for the time spent 
in completing the dysphagia questionnaire during the randomized 6 month study duration 
4. Patients who participate in the prospective observational study, and who either chose self-
dilation or observation will receive stipend of $25 for each questionnaire for the time spent in 
completing the dysphagia questionnaire 
Patients who agree to the prospective extension study will receive a stipend of $25 for each of 
the 4 monthly MDQ phone calls to collect questionnaires. 
Statistical Analysis: 
Sample Size Estimation: 
Based on the current knowledge from our prior experience, the clinical success of ESDT 
appears to be 80%. The clinical success of repetitive endoscopic dilation is reported in the 
literature to be 30%. Assuming a 50% improvement in clinical success with ESDT and using 1:1 
randomizing, the estimated minimum number of patients needed is 30 patients (15 in each 
group). Given the extreme paucity of data on self dilation and ambiguity about the potential 
improvement we intend to recruit 40 patients across the two sites (Rochester and Phoenix).This 
estimated number will provide at least 80% power of finding a significant difference at a P value 
of 0.05  
Up to 40 patients who chose not to participate in the randomized trial, but who agree to 
be followed in the prospective observational group will be recruited. 
 
 
The following table summarizes the key questions and corresponding approaches to be 
addressed by this study.   
 
Primary Endpoint: 
1. Compare the number of endoscopies required in a 6 month interval in patients who 
achieved at least a 10-12 mm esophageal diameter during serial dilation for RBES and 
were subsequently treated with ESDT versus standard clinical care.  
 
Secondary Endpoints: 
 
1. Determine the length of intervention free interval 
 
2. Dysphagia score  
 
3. Number of clinically significant adverse events including perforation, bleeding and pain 
  
4. Cost of ESDT compared to the current standard of care (repetitive endoscopic dilation) 

 
Definition: 
Perforation will be defined as Evidence of air or luminal contents outside the GI tract.  
Bleeding will be defined as hematemesis and/or melena or hemoglobin drop >2 g/L 
 
Question 
Approach 
Statistical Test 
Clinical success  
Compare the number of 
patients who remained free 
of endoscopic therapy 
between the two groups 
Logistic regression in a 
univariate and multivariate 
analysis 
Time to the next endoscopy 
Compare time endoscopic 
therapy. Patients who 
requires endoscopic dilation 
will be considered failure  
Cox regression and Kaplan 
Meier  
Adverse events 
Compare the number of 
patients who developed 
adverse events between the 
two groups  
Logistic regression in a 
univariate and multivariate 
analysis 
The cost 
Compare the cost of 
treatment including 
endoscopic therapy, 
hospitalization from 
complications  
Linear regression  
Factors affecting clinical 
success in ESDT 
Investigating factors which 
could determine clinical 
success including age, 
gender, etiology, length of 
the stricture and location of 
the stricture 
Multivariate logistic regression  
 
 
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