Obstetrics and Gynecology Devices Panel - March 27-28, 2006
The Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee met on March 27-28, 2006, in Gaithersburg, MD.
On March 27, 2006, the panel discussed the pre-market approval application (PMA P050011) from Innovata plc (Farnham, Surrey, England) for the Adept ® Adhesion Reduction Solution (4% Icodextrin). The proposed Indication for Use for the Adept ® Adhesion Reduction Solution is use as “an adjunct to good surgical technique for the reduction of post-surgical adhesions in patients undergoing gynecological laparoscopic surgery which may include adhesiolysis. Adept® should be used as both an intra-operative irrigant and post-operative instillate during the surgery.”
Adept ® Adhesion Reduction Solution (4% Icodextrin) is a single use, sterile, clear, and colorless to pale yellow fluid for intraperitoneal administration. Icodextrin is an a-1, 4-linked glucose polymer, provided at a concentration of 4% w/v in an electrolyte solution.
The panel considered the sponsor’s pivotal study, which looked at the use of Adept ® Adhesion Reduction Solution (4% Icodextrin) as an adjunct to good surgical technique for the reduction of post-surgical adhesions in patients undergoing gynecological laparoscopic surgery that included adhesiolysis . The pivotal study was a prospective, randomized, controlled, double-blinded, multi-center clinical trial. After giving informed consent, study subjects underwent planned laparoscopic, gynecologic surgery. Subjects who had at least 3 anatomic sites with adhesions (an intraoperative determination) were eligible for randomization to use of either Adept or lactated Ringer’s solution for irrigation (and aspiration) every 30 minutes intraoperatively, and for instillation (1 L) prior to closing. Adhesions were videotaped and scored prior to any or other surgical procedure. Four to eight weeks later, the subject underwent a second look laparoscopy to evaluate the patient for reformed and de novo adhesions. Primary and secondary study endpoints related to the difference between the sites with adhesions at second look compared to the first look laparoscopy.
The panel voted 10-0 recommending approval of the PMA for the Adept ® Adhesion Reduction Solution (4% Icodextrin), subject to the following nine conditions:
- Modify the proposed indication for use of Adept ® Adhesion Reduction Solution (4% Icodextrin) by limiting its use to laparoscopic surgery patients undergoing adhesiolysis. The new indication would read:
“Adept ®Adhesion Reduction Solution is intended for use as an adjunct to good surgical technique for the reduction of post-surgical adhesions in patients undergoing gynecologic laparoscopic adhesiolysis. Adept ® should be used as both an intra-operative irrigant and post-operative instillate during the surgery.”
- Revise an existing precaution to state that Adept ® Adhesion Reduction Solution has not been studied where there is a breach in the vaginal epithelium. The revised precaution statement would read:
“The safety of Adept ® has not been established after unintentional enterotomy, bowel perforation or breach of the vaginal epithelium.”
- Revise an existing precaution to state that Adept ® Adhesion Reduction Solution has not been evaluated in prevention of primary adhesions. The revised precaution statement would read:
“The safety and effectiveness of Adept ® has not been evaluated in clinical studies in the presence of frank infection in the abdominopelvic cavity or in the primary prevention of adhesions.”
- Revise an existing precaution to add adverse events of labial edema/swelling, urinary retention following use of Adept ® Adhesion Reduction Solution. The revised precaution statement would read:
“Labial edema/swelling, urinary retention or pleural effusion may present as a self limited symptom which should resolve without intervention.”
- Revise the definition for success of the first co-primary endpoint to indicate that primary efficacy was defined as the proportion of patients for whom the number of sites with adhesions decreased by at least the larger of three sites or 30% of the number of sites lysed. The revised definition would not include the term “success rate” or “clinical success” and the corresponding discussion of the first co-primary endpoint (including Figure 1) would be modified to correspond with the revised language for the first co-primary endpoint.
- All secondary endpoints should be presented in the labeling (See #8 below) with the p‑values associated with the comparison between the two arms to show whether the trend was in favor of Adept, LRS, or not at all.
- Revise the Directions for Use introduction by deleting reference to, “remove all packs and sponges.” The reference to packs and sponges implies that this material could also be used in laparotomy.
- The discussion of the secondary endpoints should be modified by replacing the discussion of the endpoints with the table (Pivotal Study: Secondary Effectiveness Endpoints (PP), Ref. Table 13) presented to the Panel within discussion question number 2, secondary endpoints.
- Revise the discussion of adverse events (paragraph #5) by deleting the parenthetical statement that reads, “(The vaginal bleeding events were not considered to be related to ADEPT or control and none was considered to be severe.)”
On March 28, 2006, the panel met to discuss a general topics matter regarding clinical trial designs for devices intended to treat symptomatic fibroids. The FDA presented the panel with an overview of its regulatory concerns about how to apply the right study design for the varying technologies under development for treatment of fibroids. In addition, FDA presented six discussion questions for the panel on appropriate assessment parameters (e.g., bleeding score, fibroid mass, quality of life measurement, etc.), study inclusion/exclusion criteria, study definitions of success, appropriate study control arms, and patient follow-up periods.
Following the presentation by FDA, the panel heard eight presentations from device manufacturers and clinical investigators who want to study new fibroid treatment modalities. After that, the panel addressed FDA’s six discussion questions. The panel provided comments on clinical trial design, addressing elements of study population, outcome measures, controls, and length of follow-up. FDA will use this input to help guide manufacturers who are developing new devices to treat fibroids.
Contact: Michael T. Bailey, Ph.D., Executive Secretary, 301-594-1180, x130.
Transcripts of this meeting may be purchased from:
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