Prospective, Multicenter, Randomized Controlled Study to Evaluate the Effect of INTERCEED™

Study Overview
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Brief Summary
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This is a prospective, randomized controlled study. The study population will include 220 subjects scheduled to undergo laparoscopic radical resection of rectal carcinoma with preventive ileostomy (Phase 1 operation). During the Phase 1 operation, when the definite decision to create a temporary ostomy is made, patients will be randomized in 1:1 ratio to either the treatment arm (INTERCEED™) or the control arm (standard of care treatment: no adhesion barrier, no placebo). In subjects assigned to the treatment arm, the INTERCEED™ must be applied beneath the target incision site (the midline incision mainly for the removal specimen). The subjects will return 3-9 months after the phase 1 operation (colorectal resection with temporary ileostomy) for phase 2 operation, to have their diverting ostomy taken down (ileostomy reversal). During the phase 2 operation (ileostomy reversal), the incidence, extent and severity of adhesions will be evaluated through the laparoscope.

Detailed Description
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This is a prospective, randomized controlled study. The study population will include 220 subjects scheduled to undergo laparoscopic radical resection of rectal carcinoma with preventive ileostomy (Phase 1 operation). During the Phase 1 operation, when the definite decision to create a temporary ostomy is made, patients will be randomized in 1:1 ratio to either the treatment arm (INTERCEED™) or the control arm (standard of care treatment: no adhesion barrier, no placebo). In subjects assigned to the treatment arm, the INTERCEED™ must be applied beneath the target incision site (the midline incision mainly for the removal specimen). The subjects will return 3-9 months after the phase 1 operation (colorectal resection with temporary ileostomy) for phase 2 operation, to have their diverting ostomy taken down (ileostomy reversal). During the phase 2 operation (ileostomy reversal), the incidence, extent and severity of adhesions will be evaluated through the laparoscope. An ad-hoc interim analysis is proposed based on feedback received from the investigators who observed very low rate of adhesions at the second procedure for ostomy reversal. The ad-hoc interim analysis is planned to be performed while at least 61% of the total number of participants with evaluable primary endpoints are available. If the conditional power (CP) is ≤ 60%, the observed adhesion rate difference magnitude is much less than the assumed difference magnitude of 0.25, therefore, the study will be terminated due to low adhesion rate and small effect size between INTERCEED and control arms. Otherwise, the study will continue until the study completion as planned.

Official Title
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A Prospective, Multicenter, Randomized Controlled Study to Evaluate the Effect of GYNECARE INTERCEED™ Absorbable Adhesion Barrier in Preventing the Abdominal Incision Adhesions

Conditions
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Subjects Scheduled to Undergo Laparoscopic Radical Resection of Rectal Carcinoma With Preventive Ileostomy

Intervention / Treatment
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* Device: INTERCEED™
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects elder than 18 years of age who require laparoscopic colorectal resection with the formation of a temporary diverting loop ileostomy and a planned closure of diverting ileostomy within 3 to 7 months The subjects should be willing to participate in the study, comply with study requirements, follow-up schedule, and give written informed consent prior to any study-related procedures The target incision length less than 8cm allowing the INTERCEED (product length 10.2cm) to overlap at least 1cm beyond each pole of the incision The subject is believed to have life expectancy more than 12 months after Phase 1 operation, based on investigators assessment. Exclusion Criteria Female patients who are pregnant or lactating at the time of screening Patient with a history of mechanical bowel obstruction but except the mechanical bowel obstruction caused by the colorectal cancer treated in the Phase I operation. Subjects with history of mid and lower abdominal region or pelvic surgery Patients for whom it is known that loop ileostomy closure within 3 to 9 months is not feasible Patients with a history of active intra-abdominal infection such as peritonitis or abdominal abscess Patients with a history of intestinal fistulae Patients with a history of endometriosis Intended use of intraoperative lavage/irrigation with any anti-adhesion solutions other than saline or an adhesion barrier other than INTERCEED Use of immune system suppressants deemed by the investigator to interfere with wound healing Impaired immune system function or coagulation disorders deemed by the surgeon to interfere with wound healing. Bevacizumab use within 30 days prior to surgery Subjects with any intra-operative findings identified by the surgeon that may preclude conduct of the study procedures Patients with evidence of distant metastasis of the primary colorectal cancer Patients who underwent abdominal radiotherapy before Phase 1 operation Adhesions (Grade 2-3 adhesion) and/or gross contamination (caused by tumor perforation) present in the abdominal cavity at the Phase 1 operation The rectal carcinoma radical resection (R0 resection) preventive ileostomy are not performed in Phase 1 operation pected resection of other organs (bladder, uterus) during Phase 1 operation Use of topical haemostatic products, local motherapeutic products or other drugs and/or medical device in abdominal/pelvic cavity which may impact the study primary endpoint judged by the investigator Patient is participating in other investigational drug or device study within 30 days or 5 half-lives of an investigational drug A known history of severe multiple drug allergies or known allergy to cellulose or cellulose derived products Any medications, treatments and/or implanted devices (except INTERCEED) that on investigator's opinion may be adhesiogenic or may potentially affect the observation of postoperative adhesions Any physical or psychological conditions that at discretion of investigators may impair study participation A medical condition or other serious conditions that will interfere with compliance and/or ability to complete this study protocol; or Any other situation or reason that at discretion of investigators is unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INTERCEED™<br>patients will be randomized in 1:1 ratio to either the treatment arm (INTERCEED™) or the control arm (standard of care treatment: no adhesion barrier, no placebo). In subjects assigned to the treatment arm, the INTERCEED™ must be applied beneath the target incision site (the midline incision mainly for the removal specimen). | Device: INTERCEED™<br>* when the definite decision to create a temporary ostomy is made, patients will be randomized in 1:1 ratio to either the treatment arm (INTERCEED™) or the control arm (standard of care treatment: no adhesion barrier, no placebo). In subjects assigned to the treatment arm, the INTERCEED™ must be applied beneath the target incision site (the midline incision mainly for the removal specimen)<br>|
| Placebo Comparator: standard of care treatment<br>During the Phase 1 operation, when the definite decision to create a temporary ostomy is made, patients will be randomized in 1:1 ratio to either the treatment arm (INTERCEED™) or the control arm (standard of care treatment: no adhesion barrier, no placebo). | Device: Placebo<br>* During the Phase 1 operation, when the definite decision to create a temporary ostomy is made, patients will be randomized in 1:1 ratio to either the treatment arm (INTERCEED™) or the control arm (standard of care treatment: no adhesion barrier, no placebo).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Free of Adhesions at the Target Incision Site | Percentage of participants free of adhesions at the target incision site in each study group based on evaluation through laparoscopy at ileostomy reversal were reported. | 3 to 9 months after phase 1 operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Extent of Adhesions at Target Incision Site in Phase 2 Operation | Number of participants with extent of adhesions at target incision site in Phase 2 operation were reported. The extent of adhesions (percentage of the area covered by adhesion) was evaluated based on Grade 1: mild, covering up to 25 percent (%) of the total area and length; Grade 2: moderate, covering 26%-50% of the total area and length; and Grade 3: severe, covering over 50% of the total area and length. | 3 to 6 months after phase 1 operation | 
| Number of Participants With Severity of Adhesions at Target Incision Site in Phase 2 Operation | Number of participants with severity of adhesions at target incision site in Phase 2 operation were reported. The severity of adhesions was evaluated based on Grade 1: filmy thickness, avascular; Grade 2: moderate thickness, limited vascularity and Grade 3: dense thickness, vascularized. | 3 to 9 months after phase 1 operation | 
| Number of Participants With Extent of Adhesions at Four Abdominal Quadrants in Phase 2 Operation | Number of participants with extent of adhesions at four abdominal quadrants in Phase 2 operation were reported. The abdominal cavity was divided into four abdominal quadrants as: Right upper abdominal quadrant, Left upper abdominal quadrant, Right lower abdominal quadrant and Left lower abdominal quadrant and the extent of adhesions (percentage of the area covered by adhesion) was evaluated based on Grade 1: mild, covering up to 25% of the total area and length; Grade 2: moderate, covering 26%-50% of the total area and length; and Grade 3: severe, covering over 50% of the total area and length. One participant may have multiple sites of adhesion. | 3 to 9 months after phase 1 operation | 
| Number of Participants With Severity of Adhesions at Four Abdominal Quadrants in Phase 2 Operation | Number of participants with severity of adhesions at four abdominal quadrants in Phase 2 operation were reported. The abdominal cavity was divided into four abdominal quadrants as: Right upper abdominal quadrant, Left upper abdominal quadrant, Right lower abdominal quadrant and Left lower abdominal quadrant and the severity of adhesions was evaluated based on Grade 1: filmy thickness, avascular; Grade 2: moderate thickness, limited vascularity and Grade 3: dense thickness, vascularized. One participant may have multiple sites of adhesion. | 3 to 6 months after phase 1 operation | 
| Number of Participants With Mechanical Ileus | Number of participants with mechanical ileus were reported. Incidence of mechanical ileus was defined as the mechanical ileus judged by investigators, which occurred 1 week after Phase 1 operation. Incidence of mechanical ileus was reported based on three categories: Post-Phase 1 operation through 7 days after Phase 1 operation (less than or equal to [<=] 7 days) (for participants underwent Phase 1 operation), 7 days after Phase 1 operation through pre-Phase 2 operation (for participants underwent Phase 1 operation) and Post-Phase 2 operation (for participants underwent Phase 2 operation). | Up to 9 months after phase 1 operation |