Seprafilm Slurry in the Prevention of Uterine Scarring in Patients Undergoing Hysteroscopic Myomectomy
Study Details
Study Description
Brief Summary
Seprafilm is an FDA-approved temporary bioresorbable barrier that physically separates opposing tissue surfaces. The physical presence of the membrane separates adhesiogenic tissue while the normal tissue repair process takes place. When used in the abdominopelvic cavity, it has been shown to reduce the incidence of adhesions.
The intrauterine cavity is a potential space where the walls of the uterus are collapsed upon itself in the normal state. It has been demonstrated that the trauma of removing a submucosal fibroid with electrocautery exposes the uterus to great potential for intrauterine adhesions since the raw charred surface is directly opposed to the opposite endometrial surface. Previous studies have shown that the placement of hyaluronic acid in the intrauterine cavity after a myomectomy is not only safe, but also decreases the incidence of intrauterine adhesions.
The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that they will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, the investigators anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
The investigators will conduct a randomized controlled trial (RCT) involving patients at NewYork Presbyterian Hospital-Columbia University Medical Center and Weill Medical College of Cornell University. The investigators will enroll 328 pre- menopausal patients (>18years) with documented submucosal myomas undergoing hysteroscopic myomectomy with monopolar resection in this study.
The investigators anticipate that approximately 30% of the patients undergoing myomectomy will form intrauterine adhesions and that administration of the Seprafilm slurry will reduce the incidence to approximately 15%.
Patients will be queried on post-operative days 1, 7, and 30 for pain/discomfort and the degree of intrauterine adhesions will be assessed after the patient's second menses (75-90 days post procedure).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Seprafilm Slurry The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that we will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, we anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state. |
Device: Seprafilm
Seprafilm Adhesion Barrier (membrane) is a sterile, bioresorbable, translucent adhesion barrier composed of two anionic polysaccharides, sodium hyaluronate (HA) and carboxymethylcellulose (CMC). Together, these biopolymers have been chemically modified with the activating agent 1-(3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC).
|
| Placebo Comparator: Placebo For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. |
Device: Sterile Saline Solution
For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline.
|
Outcome Measures
Primary Outcome Measures
- Presence of Iatrogenic Intrauterine Adhesions [2- 3 months after surgery]
Number of Subjects with iatrogenic intrauterine adhesions. Evidence of uterine scarring will be evaluated by a 3D sonohysterogram. A 3D sonohysterogram will be performed in the standard fashion in our ultrasound department by a blinded practitioner. The degree of adhesive disease will be scored by standard convention as: Absent Adhesive Disease: no presence of intrauterine adhesions Mild Adhesive Disease: cavities that are less than or equal to 30% affected Moderate Adhesive Disease: cavities that are greater than 30% but less than or equal to 60% affected Severe Adhesive Disease: cavities that are greater than 60% affected
Secondary Outcome Measures
- Pregnancy Within 12 Months of Treatment [Up to 12 months after surgery]
Number of pregnancies within 12 months of treatment. In order to determine if Seprafilm helps improve pregnancy rates we will be conducting an additional follow-up phone call up to 12 months from the day of sonohysterogram. In women who have wished to get pregnant we will ask if they have been trying to get pregnant and if they have gotten pregnant. Participation in this follow up call is optional.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Reproductive aged women: Age 18-48 years old
-
Non-pregnant
-
Otherwise healthy
-
Regular menstrual cycle
-
Documented submucosal myomas (one or more)
-
Undergoing hysteroscopic myomectomy
-
Patients must have signed an informed consent.
Exclusion Criteria:
-
Age < 18 or in menopause
-
Undergoing a second uterine surgical procedure
-
Other significant uterine pathology (including but not limited to adhesions, septae, or cancerous lesions)
-
Hysteroscopic evidence of synechiae at the time of the procedure
-
Surgeries complicated by excessive bleeding; defined by estimated blood loss > 100cc given that the presence of excessive bleeding may predispose a patient to the formation of intrauterine adhesions
-
Surgeries complicated by uterine perforation
-
Surgeries complicated by postoperative intrauterine infection given that infection may predispose a patient to the formation of intrauterine adhesions (If these patients received Seprafilm Slurry, they will continue to be followed for safety monitoring)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Weill Medical College of Cornell University | New York | New York | United States | 10021 |
| 2 | Columbia University Medical Center | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- Genzyme, a Sanofi Company
Investigators
- Principal Investigator: Rogerio A Lobo, MD, Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AAAF2293
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 11 signed a consent form, but only 8 were randomized. |
| Arm/Group Title | Seprafilm Slurry | Placebo |
|---|---|---|
| Arm/Group Description | The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that we will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, we anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state. Seprafilm: Seprafilm Adhesion Barrier (membrane) is a sterile, bioresorbable, translucent adhesion barrier composed of two anionic polysaccharides, sodium hyaluronate (HA) and carboxymethylcellulose (CMC). Together, these biopolymers have been chemically modified with the activating agent 1-(3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC). | For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. Sterile Saline Solution: For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. |
| Period Title: Overall Study | ||
| STARTED | 1 | 7 |
| COMPLETED | 1 | 7 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Seprafilm Slurry | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that we will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, we anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state. Seprafilm: Seprafilm Adhesion Barrier (membrane) is a sterile, bioresorbable, translucent adhesion barrier composed of two anionic polysaccharides, sodium hyaluronate (HA) and carboxymethylcellulose (CMC). Together, these biopolymers have been chemically modified with the activating agent 1-(3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC). | For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. Sterile Saline Solution: For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. | Total of all reporting groups |
| Overall Participants | 1 | 7 | 8 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
1
100%
|
7
100%
|
8
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
100%
|
7
100%
|
8
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
28.6%
|
2
25%
|
| White |
1
100%
|
3
42.9%
|
4
50%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
2
28.6%
|
2
25%
|
Outcome Measures
| Title | Presence of Iatrogenic Intrauterine Adhesions |
|---|---|
| Description | Number of Subjects with iatrogenic intrauterine adhesions. Evidence of uterine scarring will be evaluated by a 3D sonohysterogram. A 3D sonohysterogram will be performed in the standard fashion in our ultrasound department by a blinded practitioner. The degree of adhesive disease will be scored by standard convention as: Absent Adhesive Disease: no presence of intrauterine adhesions Mild Adhesive Disease: cavities that are less than or equal to 30% affected Moderate Adhesive Disease: cavities that are greater than 30% but less than or equal to 60% affected Severe Adhesive Disease: cavities that are greater than 60% affected |
| Time Frame | 2- 3 months after surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only 5 out of the 8 enrolled completed the 3D sonohysterograms and therefore were the only ones included in the data analysis for the primary outcome measure. |
| Arm/Group Title | Seprafilm Slurry | Placebo |
|---|---|---|
| Arm/Group Description | The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that we will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, we anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state. Seprafilm: Seprafilm Adhesion Barrier (membrane) is a sterile, bioresorbable, translucent adhesion barrier composed of two anionic polysaccharides, sodium hyaluronate (HA) and carboxymethylcellulose (CMC). Together, these biopolymers have been chemically modified with the activating agent 1-(3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC). | For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. Sterile Saline Solution: For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. |
| Measure Participants | 1 | 4 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Pregnancy Within 12 Months of Treatment |
|---|---|
| Description | Number of pregnancies within 12 months of treatment. In order to determine if Seprafilm helps improve pregnancy rates we will be conducting an additional follow-up phone call up to 12 months from the day of sonohysterogram. In women who have wished to get pregnant we will ask if they have been trying to get pregnant and if they have gotten pregnant. Participation in this follow up call is optional. |
| Time Frame | Up to 12 months after surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only 3 out of the 8 randomized completed the fertility follow up. There were 2 subjects (1 in the treatment arm and 1 in the placebo arm) who were not actively trying to get pregnant, and therefore did not complete the fertility follow up. |
| Arm/Group Title | Seprafilm Slurry | Placebo |
|---|---|---|
| Arm/Group Description | The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that we will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, we anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state. Seprafilm: Seprafilm Adhesion Barrier (membrane) is a sterile, bioresorbable, translucent adhesion barrier composed of two anionic polysaccharides, sodium hyaluronate (HA) and carboxymethylcellulose (CMC). Together, these biopolymers have been chemically modified with the activating agent 1-(3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC). | For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. Sterile Saline Solution: For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. |
| Measure Participants | 1 | 2 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Post-operative Day 1, Post-operative Day 7, and Post-operative Day 30 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Seprafilm Slurry | Placebo | ||
| Arm/Group Description | The investigators hypothesize that by placing a slurry of Seprafilm in the intrauterine cavity and creating a temporary physical barrier between the walls of the uterus, that we will be able to prevent iatrogenic intrauterine adhesions. Given that approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week, we anticipate that the patient will have minimal to no discomfort; since no physical device is being left in the endometrial cavity, the uterus will not be contracting more than it does in its normal postoperative state. Seprafilm: Seprafilm Adhesion Barrier (membrane) is a sterile, bioresorbable, translucent adhesion barrier composed of two anionic polysaccharides, sodium hyaluronate (HA) and carboxymethylcellulose (CMC). Together, these biopolymers have been chemically modified with the activating agent 1-(3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC). | For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. Sterile Saline Solution: For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline. | ||
All Cause Mortality |
||||
| Seprafilm Slurry | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 0/7 (0%) | ||
Serious Adverse Events |
||||
| Seprafilm Slurry | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 0/7 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Seprafilm Slurry | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | 7/7 (100%) | ||
| General disorders | ||||
| Fever | 1/1 (100%) | 1/7 (14.3%) | ||
| Pelvic Pain | 0/1 (0%) | 3/7 (42.9%) | ||
| Reproductive system and breast disorders | ||||
| Uterine Cramps | 1/1 (100%) | 5/7 (71.4%) | ||
| Vaginal Bleeding | 0/1 (0%) | 6/7 (85.7%) | ||
| Vaginal Discharge | 1/1 (100%) | 7/7 (100%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Flu | 1/1 (100%) | 0/7 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Sr. Research Compliance Specialist |
|---|---|
| Organization | Weill Cornell Medicine |
| Phone | 646-962-4065 |
| lao2003@med.cornell.edu |
- AAAF2293