Clinical trial NCT03350217: A Comparison of Eleview Versus Hetastarch as Injectate for EMR
Official title: A Randomized, Double-blind, Comparative, Effectiveness and Safety Study of Eleview vs. Hetastarch in Subjects Undergoing Endoscopic Mucosal Resection (EMR) of Colonic Lesions Equal to or Larger Than 11mm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Procedural Bleeding
Delayed Bleeding
Post-Polypectomy Syndrome
Post Procedural Complication
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2017-11-22
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: EMR is a technique used for the removal of flat or sessile neoplasms confined to the superficial layers of the GI tract using a snare. Injection-assisted EMR is commonly used during resections of larger flat lesions as it provides submucosal lift of polyps, adenomas, other gastrointestinal mucosal lesions or early-stage cancers prior to EMR. This has been found to minimize mechanical or electrocautery damage to the deep layers of the gastrointestinal tract wall as the injectate provides a "safety cushion" as such between the area to be removed and healthy mucosal tissue.

Several solutions are used today for injecting lesions including saline, hyaluronic acid, and hydroxyethyl starch (Hetastarch). Saline solution has been found to dissipate within minutes, which may result in a lower quality lesion lift. Hyaluronic acid provides a longer lift, but is expensive and is not readily available in the U.S.

A new injectate known as Eleview has been developed for use in gastrointestinal endoscopic procedures and recently approved by the FDA. This injectate boasts a cushion of excellent height and duration through the use of an oil-in-water emulsion. However, the initial cost of this material is quite high ($80 per 10 ml).

Hetastarch, which is the current injectate used by Dr Rex, is a safe and considerably inexpensive solution that provides prolonged submucosal elevation and lowers procedure times. Our study will aim to compare Eleview to Hetastarch in the hopes of finding the ideal submucosal injectate.

This trial will focus on polyps of size ≥11 mm removed by snare EMR technique. Patients with lesions deemed not suitable for EMR due to features suggestive of sub-mucosal invasion will not be included.

Detailed description: Injectate randomization:

Study patients will be randomly assigned to the Eleview or the Hetastarch treatment group in a 1:1 ratio. Randomization will occur at the site using envelopes provided by the Investigator. The envelope's contents will specify the treatment assignment for each patient and opened by the research team (PI will be blinded). The investigators will monitor the safety and effectiveness data. The appropriate solutions will be injected into the submucosal space beneath the lesion(s) to be excised before the lesion(s) is/are removed. Subjects in both groups will receive the appropriate volume of injectate deemed necessary by the PI for the individual patient.

Sample size and Statistical Analysis At least 200 patients will be enrolled. 100 of these patients will be randomized to Eleview injectate and 100 will be given the standard of care, Hetastarch injectate only. Efficacy and safety of Eleview injectate has only been reviewed in one previous study. Therefore, the planned sample size was not calculated using a statistical power analysis, but was regarded as sufficient to repeat the objectives of the COSMO study (2017) and satisfy the exploratory purposes of the present study.

Study personnel will carry out a simple randomization using a commonly used online generator. Randomization assignments will then be sealed until day of procedure until patient eligibility has been confirmed. The Principal Investigator will remain blinded and will perform all data analysis after completion of the study.

Data will be summarized and compared using classic descriptive statistics, i.e. mean, standard deviation, coefficient of variation (%), minimum, median and maximum values for quantitative variables, and frequencies for qualitative variables.

The Sydney Resection Quotient will be compared between treatment groups using a Wilcoxon Rank-Sum test. The proportion of subjects with en bloc resection of all endoscopically visible lesions will also be compared between treatment groups using a Fisher's exact test. A nominal alpha level of 0.05 will be used for both the comparisons.

No formal comparison will be performed for the secondary endpoints.

Eligibility criteria: Inclusion Criteria:

1. Sex and age: men and women \> 18 years old
2. Subjects referred for EMR of polyps of size ≥11 mm
3. ASA score 1, 2 or 3.
4. Contraception: Women of childbearing potential must have a negative pregnancy test (one is provided as the standard of care) or sign a waiver. Post-menopausal women must have been in that status for at least 1 year (per standard of care).
5. Subject is willing and able to participate in the study procedures and to understand and sign the informed consent

Exclusion Criteria:

1. Age: Subjects is under 18 years old
2. Consent: Vulnerable subjects including those who are unable to consent
3. Pregnancy: Pregnant or breastfeeding women
4. ASA score \<3
5. Physical findings: Abnormal physical findings that may interfere with the study objectives
6. Study participation: Subjects currently participating in another clinical study or previously enrolled in another clinical study in the last 30 days
7. Excluded lesions:

   * Lesions less than 11 mm in largest dimension
   * Lesions involving the muscularis propria (T2 lesions)
   * Ulcerated depressed lesions (Paris type III) or pathology proven invasive carcinoma
   * Proven malignant disease locally advanced or with metastasis
   * Active inflammatory bowel disease lesion, e.g ulcerative colitis, Crohn's disease
   * Endoscopic appearance of invasive malignancy
8. Previous partial resection or attempted resection of the lesion
9. Allergy: Proven or potential allergic reaction to study products or history of anaphylaxis to drugs
10. Severe liver disease.
11. Known or suspected gastrointestinal obstruction or perforation, active diverticulitis, toxic megacolon,
12. Inflammatory bowel disease e.g ulcerative colitis or Crohn's disease
13. Hemostasis disorders (eg Von Willebrand disease, factor V Leiden thrombophilia or haemophilia), known clotting disorder (INR\>1.5).
14. Subject with any other current serious medical conditions that would increase the risks associated with taking part in the study.
15. Patients must be advised to stop anticoagulation medications prior to the procedure per local practice guidelines and should re-start as clinically indicated after the procedure.

Primary outcomes:
measure: Sydney Resection Quotient (SRQ)
timeFrame: During the large polyp removal
Secondary outcomes:
measure: Injected Volume Needed for Initial Lesion Lift
timeFrame: During initial injection portion of large polyp removal
measure: Injected Volume Needed for Complete Removal of Lesion
timeFrame: During the large polyp removal
measure: Number of Re-injections Needed During Resection
timeFrame: During the large polyp removal
measure: Number of En Bloc Resections
timeFrame: During the large polyp removal
measure: Number of Pieces Resected Using Snares
timeFrame: During the large polyp removal
measure: Mound Concentration Diameter
timeFrame: During the large polyp removal
measure: Mound Concentration Height
timeFrame: During the large polyp removal
measure: Mound Duration
timeFrame: During the large polyp removal
measure: Ease of Injection
timeFrame: During the large polyp removal
measure: Need for Additional Treatments Relating to the Polyp Resection Such as Avulsion, Coagulation or Ablation.
timeFrame: During the large polyp removal
measure: Time Required to Remove the Lesion
timeFrame: During the large polyp removal
measure: Safety Outcomes as Assessed by Complications During or After the Procedure
timeFrame: during large polyp removal through 30 days post procedure
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
Study officials:
affiliation: Indiana University
name: Douglas Rex
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fasoulas K, Lazaraki G, Chatzimavroudis G, Paroutoglou G, Katsinelos T, Dimou E, Geros C, Zavos C, Kountouras J, Katsinelos P. Endoscopic mucosal resection of giant laterally spreading tumors with submucosal injection of hydroxyethyl starch: comparative study with normal saline solution. Surg Laparosc Endosc Percutan Tech. 2012 Jun;22(3):272-8. doi: 10.1097/SLE.0b013e318251553c.
citation: ASGE Technology Committee; Liu J, Petersen BT, Tierney WM, Chuttani R, Disario JA, Coffie JM, Mishkin DS, Shah RJ, Somogyi L, Song LM. Endoscopic banding devices. Gastrointest Endosc. 2008 Aug;68(2):217-21. doi: 10.1016/j.gie.2008.03.1121. No abstract available.
citation: ASGE Technology Committee; Hwang JH, Konda V, Abu Dayyeh BK, Chauhan SS, Enestvedt BK, Fujii-Lau LL, Komanduri S, Maple JT, Murad FM, Pannala R, Thosani NC, Banerjee S. Endoscopic mucosal resection. Gastrointest Endosc. 2015 Aug;82(2):215-26. doi: 10.1016/j.gie.2015.05.001. Epub 2015 Jun 12.
citation: Rex DK, Broadley HM, Garcia JR, Lahr RE, MacPhail ME, McWhinney CD, Searight MP, Sullivan AW, Mahajan N, Eckert GJ, Vemulapalli KC. SIC-8000 versus hetastarch as a submucosal injection fluid for EMR: a randomized controlled trial. Gastrointest Endosc. 2019 Nov;90(5):807-812. doi: 10.1016/j.gie.2019.06.040. Epub 2019 Jul 6.