Intrauterine Adhesions
Conditions
Keywords
submucosal myomas, intrauterine adhesions, hysteroscopic myomectomy, seprafilm
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.
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).
Interventions
DEVICESeprafilm
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).
DEVICESterile Saline Solution
For those randomized not to receive Seprafilm slurry, a syringe will be filled with 25ml of sterile saline.
Sponsors
Genzyme, a Sanofi Company
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 48 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
11 signed a consent form, but only 8 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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). | 1 |
| Placebo 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. | 7 |
| Total | 8 |
Baseline characteristics
| Characteristic | Seprafilm Slurry | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 7 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 7 |
| other Total, other adverse events | 1 / 1 | 7 / 7 |
| serious Total, serious adverse events | 0 / 1 | 0 / 7 |
Outcome results
Primary
Presence of Iatrogenic Intrauterine Adhesions
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seprafilm Slurry | Presence of Iatrogenic Intrauterine Adhesions | 0 Participants |
| Placebo | Presence of Iatrogenic Intrauterine Adhesions | 0 Participants |
Secondary
Pregnancy Within 12 Months of Treatment
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seprafilm Slurry | Pregnancy Within 12 Months of Treatment | 0 Participants |
| Placebo | Pregnancy Within 12 Months of Treatment | 0 Participants |