Study design
This study will be a pilot study for a prospective single-center, single-arm, interventional trial. The flowchart of the study is shown in Figure 2.
Approvals
The trial has been approved by the institutional review board of the Tohoku Certified Review Board of Tohoku University (Ministry of Health, Labor and Welfare Certified Clinical Research Review Board, Tohoku University) and is registered at jRCT (Japan Registry of Clinical Trial; jRCTs022200040, URL: https://jrct.niph.go.jp/re/reports/detail/11533).
Setting
This study will be conducted at a single center (Tohoku University Hospital) where the investigators are well experienced in the RIC technique.
Population
We will include 10 patients with small bowel stenosis. This is a pilot study to investigate the safety and feasibility of RIC for small bowel stenosis; thus, the number of patients should be as small as possible. However, a certain number of participants are necessary to evaluate the safety and feasibility. Therefore, we have set the number of patients that comprise the study population at 10.
Inclusion criteria
All the participants should meet the inclusion criteria as follows:
(1) Patients of any sex aged between 20 and 80 years
(2) Patients with benign small bowel stenosis
(3) Patients with performance Status between 0 and 2
(4) Patients who are able to provide written informed consent for participating in the study
Exclusion criteria
Participants with any of the following conditions will be excluded:
(1) Length of stenosis greater than 2 cm
(2) Presence of abscess or fistula close to the stenosis
(3) Presence of edematous rather than fibrotic stenosis
(4) Malignant stenosis
(5) Taking any anti-coagulant or anti-platelet drugs that cannot be discontinued temporally
(6) Pregnancy (including those in whom pregnancy is suspected), within 28 days after childbirth, or actively lactating
(7) History of psychiatric disease
(8) History of severe cardiopulmonary disease
(9) Those who are deemed ill-suited to the study by the lead doctor
Trial intervention
We will perform the RIC procedure in a way that is similar to that reported in previous studies [14-20]. The endoscopic electric knife used in this trial will be Flushknife BTS long-type (FUJIFILM Corporation, Tokyo, Japan), the use of which is not covered by insurance in Japan. Although we have not specified a particular BAE for this trial, we usually use a double-balloon endoscope (FUJIFILM Corporation, Tokyo, Japan), or a single-balloon endoscope (Olympus Medical Science, Tokyo, Japan) in Japan.
Outcomes
Primary outcome
The primary outcome of this study is the safety of using RIC for benign stenosis in the small intestine, and the safety is evaluated by measuring the frequency of adverse events of special interest (AESI) during one month after RIC. AESI includes complications related to RIC, such as bleeding and perforation, which require endoscopic hemostasis or surgery. Safety of RIC is selected as the primary outcome because this is a pilot study and there are no other studies reporting the safety of performing RIC in the small intestine using BAE.
Secondary outcomes
- The technical success rate of RIC (defined by the rate of scope passage at the dilation site)
- Improvement in subjective symptoms, which will be evaluated using the visual analog scale (VAS) or the Crohn’s disease activity index
- Duration of hospitalization
- Procedure time of RIC
We have selected these secondary outcomes to evaluate the feasibility and efficacy of performing RIC in the small intestine in this trial.
The study procedure and schedules
The SPIRIT checklist was followed as a guide for reporting this study protocol. It is shown in Figure 1. The populated SPIRIT checklist is also provided as an additional file (see Additional File 1). We will target and screen those patients who present with subjective symptoms such as abdominal bloating, vomiting, and ileus. Most of the screening examinations will be clinical. Abdominal ultrasound or magnetic resonance imaging will be employed to investigate the wall thickness at the stenotic site as much as possible. The investigators will explain the procedure of the trial to those patients who meet the criteria and will obtain written informed consent. Participants will be able to withdraw their consent to participate whenever they want. Patients’ registration will be performed using the eligibility confirmation sheet. This pilot study is a single-arm non-randomized trial; therefore, the enrollment will be accomplished after filling the confirmation sheet.
The enrolled participants will undergo the RIC procedure and will stay admitted to the hospital for around seven days after RIC. Follow-up will be conducted after one month. The occurrence of any adverse events (AEs) will be monitored during this time. Subjective symptoms including abdominal bloating, abdominal pain, and nausea will be evaluated using VAS.
Randomization and Blinding
Not applicable.
Safety
As mentioned above, the safety of RIC is the primary outcome in this study. Bleeding and perforation after RIC are the probable major AEs. Our previous report and other studies showed that delayed bleeding and perforation were the major AEs. The participants could also develop pancreatitis after EBD via the transoral approach. These AE and other complications will be monitored until one month after RIC and recorded in a case report form.
Serious adverse events (SAEs) are defined as follows:
(1) All deaths and immediate life-threatening events, whether related or unrelated to the procedure
(2) Prolongation of hospitalization
(3) Substantial disruption of normal life functions
All SAEs will be recorded as well and reported to the institutional review board and the Ministry of Health, Labor and Welfare as soon as possible.