Menorrhagia
Conditions
Keywords
heavy menstrual bleeding, endometrial ablation
Brief summary
The purpose of the study is to evaluate the safety and effectiveness of the Cerene Cryotherapy Device in reducing menstrual bleeding in women with heavy menstrual bleeding (menorrhagia) due to benign causes for whom child bearing is complete.
Interventions
DEVICECerene(R) Cryotherapy Device
Sponsors
Channel Medsystems
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Refractory heavy menstrual bleeding with no definable organic cause * Female subject age 25 to 50 years, inclusive * Sounded length of uterine cavity no greater than 10 cm and endometrial cavity no greater than 6.5 cm * Sufficient myometrial thickness * Documented excessive menstrual blood loss within 3 months of informed consent * Premenopausal confirmed by follicle stimulating hormone (FSH) measurement * Agrees to use a reliable form of contraception following ablation treatment * Provides written informed consent using a form that has been approved by the reviewing ethics committee * Agrees to follow-up exams and data collection requirements * Demonstrates an understanding of how to record menstrual blood loss using a menstrual pictogram * Has predictable, cyclic menstrual cycles
Exclusion criteria
* Pregnant or has a desire to conceive * Endometrial hyperplasia as confirmed by histology * Active endometritis * Active pelvic inflammatory disease * Active sexually transmitted disease (STD) * Presence of bacteremia, sepsis, or other active systemic infection * Active infection of the genitals, vagina, cervix, or uterus * Known/suspected abdominal, pelvic, or gynecological malignancy within the past 5 years * Known clotting defects or bleeding disorders * Abnormal cytology on Human papillomavirus (HPV) testing not treated according to local standards. * Prior uterine surgery that interrupts the integrity of the uterine wall (e.g., transmural myomectomy or classical cesarean section). * Previous low transverse cesarean section where the myometrial wall thickness is insufficient * Previous endometrial ablation procedure * Clinically significant adenomyosis indicated by subject complaints, imaging, or clinician's judgment * Presence of an implantable contraceptive device * Currently on medications that could thin the myometrial muscle * Currently on anticoagulants * Abnormal or obstructed cavity * Currently using an intrauterine device (IUD) and unwilling to remove the IUD * Post-partum ≤ 6-months * Considering participation in a research study of an investigational drug or device that would begin during the course of this investigational study * Any general health or mental, or other situation or condition which, in the opinion of the Investigator, could represent an increased risk for the subject or impact the subject's ability to comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint: Number of Serious Adverse Events and Serious Device-related Adverse Events | 12 months | — |
| Primary Effectiveness Endpoint: Number of Subjects With Reduction in Menstrual Bleeding to PBLAC Score of ≤75 | 12 months | Success for the primary effectiveness endpoint was defined as reduction in menstrual bleeding to a PBLAC (Pictorial Blood Loss Assessment Chart) score of ≤75. Scale information for PBLAC (Pictorial Blood Loss Assessment Chart): The scale minimum is 0, which indicates amenorrhea, i.e. no bleeding. There is no scale maximum. A score of 100 indicates eumenorrhea, i.e. normal menstrual bleeding. A lower PBLAC score indicates less bleeding; a higher PBLAC score indicates more bleeding. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Rating of Pain During Treatment and Day One Post-Treatment | Day of Treatment and Day One Post-Treatment | Pain rating using numeric rating scale, minimum 0, maximum 10, with 0 designated as no pain and 10 designated as the worst pain. |
| Dysmennorhea | 12 Months | Subjects were queried regarding if they suffer from dysmenorrhea (painful cramping associated with menstruation). The subject was asked to rate their level of dysmenorrhea on a scale from 0 to 5, with 0 indicating no symptoms and 5 indicating very severe symptoms. A score of 0 was considered better than a score of 5. |
| Amenorrhea | 12 Months | Pictorial blood loss assessment (PBLAC) score = 0 Scale information for PBLAC (Pictorial Blood Loss Assessment Chart): The scale minimum is 0, which indicates amenorrhea, i.e. no bleeding. There is no scale maximum. A score of 100 indicates eumenorrhea, i.e. normal menstrual bleeding. A lower PBLAC score indicates less bleeding; a higher PBLAC score indicates more bleeding. |
| Investigator Evaluation of the Uterine Cavity | 12 Months | — |
| Investigator Assessment of Cavity Findings | 12 Months | Questions to the investigator |
| Anesthesia and Pain Medications at Treatment | Day of Treatment | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subject Recommendation | 36 months | Subjects' reported level of recommendation to a friend/family |
| Procedure Time | Day of Treatment | Device insertion to device removal |
| Return to Normal Daily Activities | Two-Weeks | — |
| Subjects' Report of Their Last Menstrual Period | 36 months | Subjects were asked to describe their last menstrual period |
| Menstrual Impact Questionnaire | 36 months | Subjects' Report of Activity Limitations |
| Premenstrual Symptoms Impact Survey | 36 months | Subjects' Report of Pre-Menstrual Symptoms (PMS) |
| Subject Satisfaction | 36 Months | Subject's level of satisfaction with the results of her Cerene treatment |
Countries
Canada, Mexico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Endometrial Cryoablation Cerene(R) Cryotherapy Device | 242 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Hysterectomy for fibroids | 2 |
| Overall Study | Hysterectomy for uterine prolapse | 1 |
| Overall Study | Intervention for menstrual bleeding | 17 |
| Overall Study | IUD: Mirena | 1 |
| Overall Study | Lost to Follow-up | 13 |
| Overall Study | Pregnancy | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Endometrial Cryoablation |
|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 5.1 |
| Baseline PBLAC (Pictorial Blood Loss Assessment Chart) Score | 360.6 scores on a scale STANDARD_DEVIATION 332.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants |
| Race/Ethnicity, Customized Other | 43 Participants |
| Race/Ethnicity, Customized White | 190 Participants |
| Sex: Female, Male Female | 242 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 242 |
| other Total, other adverse events | 29 / 242 |
| serious Total, serious adverse events | 6 / 242 |
Outcome results
Primary
Primary Effectiveness Endpoint: Number of Subjects With Reduction in Menstrual Bleeding to PBLAC Score of ≤75
Success for the primary effectiveness endpoint was defined as reduction in menstrual bleeding to a PBLAC (Pictorial Blood Loss Assessment Chart) score of ≤75. Scale information for PBLAC (Pictorial Blood Loss Assessment Chart): The scale minimum is 0, which indicates amenorrhea, i.e. no bleeding. There is no scale maximum. A score of 100 indicates eumenorrhea, i.e. normal menstrual bleeding. A lower PBLAC score indicates less bleeding; a higher PBLAC score indicates more bleeding.
Time frame: 12 months
Population: The Intent-to-Treat (ITT) population comprised all patients who successfully completed screening and presented on the day of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Endometrial Cryoablation | Primary Effectiveness Endpoint: Number of Subjects With Reduction in Menstrual Bleeding to PBLAC Score of ≤75 | 186 Participants |
Primary
Primary Safety Endpoint: Number of Serious Adverse Events and Serious Device-related Adverse Events
Time frame: 12 months
Population: The Intent-to-Treat (ITT) population is comprised of all patients who successfully completed screening and presented on the day of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Endometrial Cryoablation | Primary Safety Endpoint: Number of Serious Adverse Events and Serious Device-related Adverse Events | Serious device-related adverse events | 0 Reports of events |
| Endometrial Cryoablation | Primary Safety Endpoint: Number of Serious Adverse Events and Serious Device-related Adverse Events | Serious adverse events | 7 Reports of events |
Secondary
Amenorrhea
Pictorial blood loss assessment (PBLAC) score = 0 Scale information for PBLAC (Pictorial Blood Loss Assessment Chart): The scale minimum is 0, which indicates amenorrhea, i.e. no bleeding. There is no scale maximum. A score of 100 indicates eumenorrhea, i.e. normal menstrual bleeding. A lower PBLAC score indicates less bleeding; a higher PBLAC score indicates more bleeding.
Time frame: 12 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Endometrial Cryoablation | Amenorrhea | 25 Participants |
Secondary
Anesthesia and Pain Medications at Treatment
Time frame: Day of Treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Anesthesia and Pain Medications at Treatment | Paracervical block only | 20 Participants |
| Endometrial Cryoablation | Anesthesia and Pain Medications at Treatment | Paracervical block with nonsteroidal anti-inflammatories | 48 Participants |
| Endometrial Cryoablation | Anesthesia and Pain Medications at Treatment | Paracervical block with oral narcotics and/or anxiolytics | 167 Participants |
| Endometrial Cryoablation | Anesthesia and Pain Medications at Treatment | Paracervical block with intravenous sedation | 7 Participants |
| Endometrial Cryoablation | Anesthesia and Pain Medications at Treatment | General anesthesia | 0 Participants |
Secondary
Dysmennorhea
Subjects were queried regarding if they suffer from dysmenorrhea (painful cramping associated with menstruation). The subject was asked to rate their level of dysmenorrhea on a scale from 0 to 5, with 0 indicating no symptoms and 5 indicating very severe symptoms. A score of 0 was considered better than a score of 5.
Time frame: 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Dysmennorhea | 0 - No symptom | 74 Participants |
| Endometrial Cryoablation | Dysmennorhea | 1 - Very Mild | 70 Participants |
| Endometrial Cryoablation | Dysmennorhea | 2 - Mild | 40 Participants |
| Endometrial Cryoablation | Dysmennorhea | 3 - Moderate | 33 Participants |
| Endometrial Cryoablation | Dysmennorhea | 4 - Severe | 10 Participants |
| Endometrial Cryoablation | Dysmennorhea | 5 - Very Severe | 3 Participants |
Secondary
Investigator Assessment of Cavity Findings
Questions to the investigator
Time frame: 12 Months
Population: Investigators' assessment was based on the 204 subjects whose cavities could be fully visualized (see Secondary Outcome: Investigator Evaluation of the Uterine Cavity).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Endometrial Cryoablation | Investigator Assessment of Cavity Findings | Would the Investigator be able to direct a biopsy anywhere within the uterine cavity? | YES | 178 Participants |
| Endometrial Cryoablation | Investigator Assessment of Cavity Findings | Would the Investigator be able to direct a biopsy anywhere within the uterine cavity? | NO | 26 Participants |
| Endometrial Cryoablation | Investigator Assessment of Cavity Findings | Satisfied with ability to adequately visualize the endometrium to evaluate for pathologic change? | YES | 195 Participants |
| Endometrial Cryoablation | Investigator Assessment of Cavity Findings | Satisfied with ability to adequately visualize the endometrium to evaluate for pathologic change? | NO | 9 Participants |
Secondary
Investigator Evaluation of the Uterine Cavity
Time frame: 12 Months
Population: Of 230 subjects with a known Month 12 outcome, 223 underwent a hysteroscopy at Month 12. The remaining seven (7) subjects encountered scheduling conflicts or illness.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Endometrial Cryoablation | Investigator Evaluation of the Uterine Cavity | Uterine cavity entry with a hysteroscope | YES | 220 Participants |
| Endometrial Cryoablation | Investigator Evaluation of the Uterine Cavity | Uterine cavity entry with a hysteroscope | NO | 3 Participants |
| Endometrial Cryoablation | Investigator Evaluation of the Uterine Cavity | Full visualization of the uterine cavity | YES | 204 Participants |
| Endometrial Cryoablation | Investigator Evaluation of the Uterine Cavity | Full visualization of the uterine cavity | NO | 19 Participants |
Secondary
Subject Rating of Pain During Treatment and Day One Post-Treatment
Pain rating using numeric rating scale, minimum 0, maximum 10, with 0 designated as no pain and 10 designated as the worst pain.
Time frame: Day of Treatment and Day One Post-Treatment
Population: Some subjects did not provide a pain score rating due to sedation. One subject did not provide a pain score at her Day 1 visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | Before Device Insertion | 1 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | After Device Insertion | 2 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | After Liner Deployment (before endometrial ablation was initiated) | 1 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | After 1 Minute of Ablation | 2 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | End of Ablation | 1 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | 15-30 Minutes Post-Procedure | 2 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | At Time of Discharge | 2 units on a scale |
| Endometrial Cryoablation | Subject Rating of Pain During Treatment and Day One Post-Treatment | Day 1 | 0 units on a scale |
Other Pre-specified
Menstrual Impact Questionnaire
Subjects' Report of Activity Limitations
Time frame: 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Menstrual Impact Questionnaire | Free of limitation in activity at moderate or higher level | 182 Participants |
| Endometrial Cryoablation | Menstrual Impact Questionnaire | Limitation in activity is present at moderate or higher level | 19 Participants |
Other Pre-specified
Premenstrual Symptoms Impact Survey
Subjects' Report of Pre-Menstrual Symptoms (PMS)
Time frame: 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Premenstrual Symptoms Impact Survey | Free of PMS often, most often, very often, or all of the time | 171 Participants |
| Endometrial Cryoablation | Premenstrual Symptoms Impact Survey | PMS occur often, most often, very often, or all of the time | 30 Participants |
Other Pre-specified
Procedure Time
Device insertion to device removal
Time frame: Day of Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endometrial Cryoablation | Procedure Time | 6.9 minutes | Standard Deviation 1.1 |
Other Pre-specified
Return to Normal Daily Activities
Time frame: Two-Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endometrial Cryoablation | Return to Normal Daily Activities | 2.0 days | Standard Deviation 2.3 |
Other Pre-specified
Subject Recommendation
Subjects' reported level of recommendation to a friend/family
Time frame: 36 months
Population: Of 201 subjects who completed the study, 193 reported their level of recommendation
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Subject Recommendation | Definitely or maybe recommend | 175 Participants |
| Endometrial Cryoablation | Subject Recommendation | Probably not or definitely not recommend | 18 Participants |
Other Pre-specified
Subject Satisfaction
Subject's level of satisfaction with the results of her Cerene treatment
Time frame: 36 Months
Population: Of 201 subjects who completed the study, 181 reported their level of satisfaction
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Subject Satisfaction | Dissatisfied or very dissatisfied | 28 Participants |
| Endometrial Cryoablation | Subject Satisfaction | Satisfied or very satisfied | 153 Participants |
Other Pre-specified
Subjects' Report of Their Last Menstrual Period
Subjects were asked to describe their last menstrual period
Time frame: 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Endometrial Cryoablation | Subjects' Report of Their Last Menstrual Period | I no longer get my period | 29 Participants |
| Endometrial Cryoablation | Subjects' Report of Their Last Menstrual Period | My periods are lighter than normal | 99 Participants |
| Endometrial Cryoablation | Subjects' Report of Their Last Menstrual Period | My periods are normal | 50 Participants |
| Endometrial Cryoablation | Subjects' Report of Their Last Menstrual Period | I continue to have heavy periods | 23 Participants |