UMIN-CTR Clinical Trial

Basic information
Public title	Safety and efficacy of Tip-in endoscopic mucosal resection for large flat colorectal Adenomas: a Randomized control trial
Acronym	STAR trial
Scientific Title	Safety and efficacy of Tip-in endoscopic mucosal resection for large flat colorectal Adenomas: a Randomized control trial
Scientific Title:Acronym	STAR trial
Region	Japan

Condition
Condition	large flat colorectal adenomas
Classification by specialty	Gastroenterology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To assess the safety and efficacy of the Tip-in EMR technique for large flat colorectal adenomas (15-25 mm in diameter) in randomized comparison with conventional EMR method.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	En bloc resection rate in intention-to-treat analysis
Key secondary outcomes	1.En bloc resection rate in per-protocol analysis 2. Complete R0 resection rate 3. One-year accumulate recurrence rate 4. En bloc resection rate in group A (15-19 mm in diameter) and group B (20-24 mm in diameter) 5. One-year accumulate recurrence rate in group A (15-19 mm in diameter) and group B (20-24 mm in diameter) 6. Complete R0 resection rate in group A (15-19 mm in diameter) and group B (20-24 mm in diameter) 7. En bloc resection rate by lesion location 8. One-year accumulate recurrence rate in en bloc resection group and piecemeal resection group 9. One-year accumulate recurrence rate in R0 resection group and R1resection group 10. One-year accumulate recurrence rate in cases of RX resection 11. Rate of exclusion by poor lesion lifting in cases with previous biopsies 12. Complication rate 13. Accuracy of endoscopic diagnosis for residual adenomas during surveillance tests

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Maneuver
Interventions/Control_1	conventional EMR
Interventions/Control_2	Tip-in EMR technique
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Patients with a large flat adenoma (15-25 mm in size) 2. Patients aged over 20 years old when consents to the participation is obtained 3. Ptients consented after full understanding of this study
Key exclusion criteria	1. Cases with clinical diagnosis of T1 cancer 2. Cases with difficulties to interrupt intake of anticoagulant drugs 3. Inappropriate cases by investigators
Target sample size	80

Research contact person
Name of lead principal investigator	1st name Kenichiro Middle name Last name Imai
Organization	Shizuoka Cancer Center
Division name	Division of Endoscopy
Zip code	411-8777
Address	1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka
TEL	055-989-5222
Email	k.imai1977@gmail.com

Public contact
Name of contact person	1st name Kenichiro Middle name Last name Imai
Organization	Shizuoka Cancer Center
Division name	Division of Endoscopy
Zip code	411-8777
Address	1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka
TEL	055-989-5222
Homepage URL
Email	k.imai1977@gmail.com

Sponsor
Institute	Division of Endoscopy, Shizuoka Cancer Center
Institute
Department

Funding Source
Organization	Division of Endoscopy, Shizuoka Cancer Center
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Shizuoka Cancer Center
Address	1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
Tel	055-989-5222
Email	ke.imai@scchr.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2017 Year 02 Month 14 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	85
Results	We analyzed 41 lesions in the Tipin EMR group and 41 lesions in the EMR group. En bloc resection was achieved in 37 (90.2 percent) patients in the Tipin EMR group and 30 (73.1 percent) in the EMR group. The adjusted odds ratio of en bloc resection in Tip-in EMR vs. EMR was 3.46 (95 percent CI 1.06 to 13.6) with a significant difference (P 0.040). There were no differences between Tipin EMR and EMR in adverse events (0 vs 4.8 percent) and median procedure time (7 vs 5 min).
Results date posted	2021 Year 02 Month 02 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	There were no differences between the two groups in median tumor size, size distribution category, location, morphology, and LST subtype (Table 1). Biopsy had previously been attempted in 5 (12.2%) cases in the CEMR group and in 13 (31.7%) in the Tip-in EMR group. At EMR, lesion lifting after submucosal injection was poor in 7 (17.1%) in the CEMR group and 10 (24.4%) in the Tip-in EMR group.
Participant flow	From February 2017 to August 2018, a total of 234 colorectal lesions were assessed for study eligibility during colonoscopy at our institution and a total of 85 lesions were enrolled (Figure 2). With regards to group allocation, 42 lesions were assigned to the CEMR group and 43 to the Tip-in EMR group. After randomization, EMR was not carried out due to patient consent withdrawal in one case in each group because the patients and their families had hoped to receive the ESD treatment to assure complete resection and were hesitant to receive the frequent surveillance colonoscopies in the study protocol. Another lesion was strongly suspected to be deeply invasive submucosal cancer just prior to Tip-in EMR and transferred to ESD. The ESD specimen revealed deep invasive cancer, thus this patient was referred for additional surgery. Finally, 41 lesions (25 in the 15 to 20 mm and 16 in the 21 to 25 mm size category) in the CEMR group and 41 lesions (24 in the 15 to 20 mm and 17 in the 21 to 25 mm size category) in the Tip-in EMR group were included in the analysis.
Adverse events	There was no evidence of differences in adverse-event rates including bleeding and perforation between CEMR and Tip-in EMR (Table 5). After EMR, snare-tip coagulation was performed as hemostasis for intraprocedural oozing in 1 CEMR patient. Emergent endoscopy was done for 1 case with hematochezia 2 days after CEMR. Bleeding stopped spontaneously and prophylactic clip closure of the defect was completed.
Outcome measures	In the intention to treat analysis, en bloc resection was achieved in 30 (73.1 percent) lesions in the CEMR group and 37 (90.2 percent) in the Tip-in EMR group. The adjusted odds ratio of en bloc resection of Tip-in EMR vs CEMR was 3.46 (95 percent confidence interval 1.06 to 13.6) with a significant difference (P = 0.040; Table 2). After initial snaring, residual neoplasms were identified in 11 (26.9 percent) patients in the CEMR group and in 4 (9.8%) in the Tip-in EMR group. Additional snare resection was done with a median of 2 snare resections in 9 (22.0 percent) lesions in the CEMR group and 4 (9.8 percent) in the Tip-in EMR group. Cold biopsies were added to the initial resection in 2 (4.9 percent) lesions in the CEMR group. Median procedure time was similar between the two groups (5 vs 7 min, Table 3). The completion of resection was confirmed by NBIME in all cases. Recurrence at 6-month SC in 15 CEMR and in 8 Tipin EMR lesions was detected in 1 of each group after piecemeal resection. Residual tumors were removed by cold forceps polypectomy. Recurrence at 12-month SC in 38 CEMR and 35 Tipin EMR lesions was detected in 2 of the CEMR group. One was detected and removed at the 6-month SC and another was initially detected at the 12-months SC after en bloc resection with pathologically negative margins. Each residual adenoma was removed by EMR and diagnosed as low-grade tubular adenoma. The final cumulative recurrent rates were 5.2 percent (2/38) and 2.8 percent (1/35) in the CEMR and Tipin EMR group, respectively. Resection completion was predicted by NBIME in 95.9 percent (70/73, 95percent CI: 88.5 to 99.1 percent).
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2017 Year 01 Month 17 Day
Date of IRB	2017 Year 01 Month 17 Day
Anticipated trial start date	2017 Year 01 Month 29 Day
Last follow-up date	2020 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 01 Month 20 Day
Last modified on	2021 Year 02 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026835

Research Plan
Registered date	File name
2020/01/23	Tipin研究計画書第5版.pdf

Research case data specifications
Registered date	File name
2020/01/23	【先端穿刺法EMR試験】症例登録進捗状況一覧表2019年3月 のコピー.pdf

Research case data
Registered date	File name
2021/02/02	STARtrialデータUMIN登録用.xls

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