search
Back to results

Medical Therapy Versus Radiofrequency Endometrial Ablation in the Initial Treatment of Menorrhagia (iTOM)

Primary Purpose

Menorrhagia

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills
Naproxen sodium pills
NovaSure® Radiofrequency Endometrial Ablation
Sponsored by
Abimbola Famuyide
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Menorrhagia focused on measuring Menorrhagia, Endometrial ablation, Heavy menstrual bleeding

Eligibility Criteria

30 Years - 55 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adult female, ages 30-55, who is pre-menopausal and for whom childbearing is complete
  2. Subjective symptom of excessive menstrual loss
  3. Normal uterine cavity length (≥ 4cm) with a sound measurement of ≤10cm documented by sonohysterogram or hysteroscopy in the preceding 6 months
  4. At least one normal Pap Test and no unexplained abnormal Pap Tests within 6 months of procedure
  5. Prior history of permanent sterilization or use of reliable non-hormonal contraception during the 14 month study period or history of vasectomy in partner
  6. Freely agree to participate in the study including all study related procedures and evaluations, and document this agreement by signing the informed consent document

Exclusion Criteria:

  1. Pregnancy or desire for future childbearing
  2. Active lower genital infection at the time of procedure
  3. Active urinary tract infection at the time of procedure
  4. Active pelvic inflammatory disease (PID) or recurrent chronic PID
  5. Endometrial neoplasia, determined by endometrial biopsy taken within 12 months of study entry
  6. Current or past history of cervical or endometrial cancer
  7. Uterine sound measurement greater than 10cm
  8. Submucous leiomyoma greater than 2cm or cavity distorting leiomyoma
  9. History of myomectomy or classical cesarean section
  10. Previous endometrial ablation
  11. Oral hormonal treatment in the preceding 3 months, hormone releasing intrauterine contraceptive in the preceding month, or injectable hormone treatment in the preceding 12 months
  12. Contraindication to hormonal therapy and non-steroidal anti-inflammatory agents.
  13. History of a coagulopathy or endocrinopathy
  14. Inability to follow up at 12 months

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Medical Therapy

Radiofrequency Endometrial Ablation

Arm Description

Subjects will be prescribed monthly packets of Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills. Subjects who are unable to tolerate oral contraceptive pills or are unwilling to take oral contraceptive pills will be prescribed naproxen sodium pills. The latter will be administered as follows; 500mg with onset of menses, then 250mg three times daily for the duration of the menses (or maximum of five days).

Subjects will undergo NovaSure® radiofrequency endometrial ablation within 4 weeks of randomization. The procedure will occur at any time during the menstrual cycle, without endometrial pre-treatment. Endometrial thinning will be carried out using suction curettage in 50% of the cases included in the ablation group. Random assignment for this treatment will be included in the overall randomization plan.

Outcomes

Primary Outcome Measures

Menstrual Blood Loss (MBL) as Measured by Pictorial Blood Loss Assessment Chart (PBLAC).
The PBLAC is a simple, pictorial tool used in women with menorrhagia to assess menstrual blood loss. The total score is calculated by adding up the sum of all scores for the tampons or sanitary napkin used in the menstrual cycle. For tampons: 1 for lightly stained, 5 for moderately soiled and 10 for completely saturated tampons. For sanitary napkins: 1 for lightly stained, 5 for moderately soiled, and 20 for completely saturated pads. Clots were given a score of 1 for small and 5 for large clots. Abnormal PBLAC bleeding score greater than or equal to 100, which correlates with menorrhagia, defined as greater than 80 mL of menstrual blood loss. Normal bleeding is defined as a score of 75 or less. A score of 0 indicates amenorrhea, or absence of menstruation.

Secondary Outcome Measures

Quality of Life Score Using the Short Form-12 (SF-12) Health Survey
Quality of life (QoL) was measured by the SF-12 questionnaire. The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. Physical and Mental Health Composite Scores are computed (combined, scored, and weighted) using the scores of the 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. Improvement was defined as a change of ≥ 6 points.
Quality of Life as Measured by the Menorrhagia Multi-Attribute Scale (MMAS )
The MMAS questionnaire captures the subjective consequences of menorrhagia on six domains: practical difficulties; social life; psychological wellbeing; physical health; work routine; and family life. Each of the six domains has four statements that represent four levels of response. Respondents indicate the statement that best matches their feelings for each domain. The statement scores derive from a weighting of the domains and a weighting of the statements in level of severity by women in the original study. Scores range from 0 (worst possible state in all domains) to 100 (best possible state in all domains).
Hemoglobin at 12 Months
Change in Hemoglobin
Ferritin at 12 Months
Change in Ferritin From Baseline
Direct Medical Costs
Direct Medical Costs consisted of two categories: primarily hospital billed services, and primarily physician billed services. Primary hospital billed services were as defined by Medicare billing practice.
Indirect Medical Costs
Indirect cost A refers to cost of sanitary products and lack of activity, indirect cost B refers to cost of sanitary products and reduced work days, and indirect cost C refers to cost of sanitary products, lack of activity, and reduced work days.
Bleeding Pattern at 12 Months
The menstruation pattern of the subjects was evaluated. A bleeding episode was defined as any set of one or more bleeding days bounded at each end by two or more bleeding-free days. The bleeding pattern was analyzed using a 90 day reference period and divided into groups, (based on World Health Organization (WHO) classification of clinically important bleeding patterns). The groups are Amenorrhea (no bleeding during the reference period); Infrequent bleeding (fewer than 3 bleeding episodes); Irregular bleeding (between 3 and 5 episodes with less than 3 bleeding-free intervals of length 14 days or more); Prolonged bleeding (1 or more bleeding episodes lasting 14 days or more); Eumenorrhea "normal pattern" (none of the above patterns).
Pain at 12 Months as Measured by the Pain Visual Analog Scale (VAS)
The pain VAS is a continuous scale comprised of a horizontal (HVAS) line, 100 mm in length. Possible scores range from 0 (no pain) to 100 (worst possible pain). The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks.
Subject Satisfaction at 12 Months
Subject satisfaction was ascertained by asking study participants to choose from one of four categories relating to their general satisfaction with treatment: totally satisfied, generally satisfied, acceptable improvement in symptoms, or unacceptable treatment.

Full Information

First Posted
July 9, 2010
Last Updated
January 19, 2017
Sponsor
Abimbola Famuyide
Collaborators
Hologic, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01165307
Brief Title
Medical Therapy Versus Radiofrequency Endometrial Ablation in the Initial Treatment of Menorrhagia
Acronym
iTOM
Official Title
A Prospective Randomized Trial of Medical Therapy Versus Radiofrequency Endometrial Ablation in the Initial Treatment of Menorrhagia: Treatment Outcomes and Cost Utility Analysis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Abimbola Famuyide
Collaborators
Hologic, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Excessive menstrual loss (menorrhagia) is a common condition that affects women of reproductive age, and can result in anemia, chronic fatigue and lost wages from work. The traditional first line management involves treatment with oral contraceptives or non-steroidal anti-inflammatory agents. Many women ultimately undergo hysterectomy, a major operative procedure associated with increased costs, loss of feeling of womanhood, debilitating complications and on rare occasions, death. The newer global endometrial ablation (GEA) devices allow the destruction of the endometrial lining, without the removal of the uterus, in an ambulatory surgery setting. GEA offers a safe and effective alternative to hysterectomy with minimal risks and without unpleasant side-effects. Presently, global endometrial ablation is offered as an alternative to hysterectomy, after medical intervention has failed. This study will determine the role of global endometrial ablation in the initial management of menorrhagia. Women seeking treatment for menorrhagia will be randomized to either the medical treatment arm or the global endometrial ablation arm. This study will be the first to compare clinical efficacy and costs between oral contraceptive pills and global endometrial ablation in the initial management of menorrhagia and could potentially change the management of menorrhagia and impact millions of women who suffer from this condition.
Detailed Description
Goal of study: To evaluate the safety, effectiveness as well as cost- effectiveness of Global Endometrial Ablation (GEA) as an initial treatment for menorrhagia. Specific aim #1: To determine if global endometrial ablation (GEA) is more effective than medical therapy in the initial management of menorrhagia. Specific aim #2: To determine disease-specific resource utilization and costs associated with the treatment alternatives and the cost effectiveness of global endometrial ablation (GEA) compared with medical treatment (oral contraceptive pills) in the initial management of menorrhagia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menorrhagia
Keywords
Menorrhagia, Endometrial ablation, Heavy menstrual bleeding

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
77 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Medical Therapy
Arm Type
Active Comparator
Arm Description
Subjects will be prescribed monthly packets of Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills. Subjects who are unable to tolerate oral contraceptive pills or are unwilling to take oral contraceptive pills will be prescribed naproxen sodium pills. The latter will be administered as follows; 500mg with onset of menses, then 250mg three times daily for the duration of the menses (or maximum of five days).
Arm Title
Radiofrequency Endometrial Ablation
Arm Type
Active Comparator
Arm Description
Subjects will undergo NovaSure® radiofrequency endometrial ablation within 4 weeks of randomization. The procedure will occur at any time during the menstrual cycle, without endometrial pre-treatment. Endometrial thinning will be carried out using suction curettage in 50% of the cases included in the ablation group. Random assignment for this treatment will be included in the overall randomization plan.
Intervention Type
Drug
Intervention Name(s)
Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills
Other Intervention Name(s)
Nordette®
Intervention Description
Each packet consists of a fixed dose of 30mcg estradiol and a 150mcg dose of levonorgestrel for the first 21 days of the cycle, followed by a 7 day pill free period. Subjects will be instructed to administer the pills orally, starting 5 days after the start of menstrual blood flow, continuing cyclically, thus allowing for withdrawal bleeding after the 21 day pill cycle.
Intervention Type
Drug
Intervention Name(s)
Naproxen sodium pills
Other Intervention Name(s)
Naprosyn 250 mg tablets
Intervention Description
As an alternative to oral contraceptive pills, subjects may take Naproxen 500 mg with onset of menses, then 250 mg three times daily for the duration of the menses (or maximum of five days)
Intervention Type
Device
Intervention Name(s)
NovaSure® Radiofrequency Endometrial Ablation
Intervention Description
Radiofrequency endometrial ablation is performed in the outpatient surgery department. Subjects receive intravenous medication, determined by the attending anesthesiologist, sufficient to induce conscious sedation during the procedure.
Primary Outcome Measure Information:
Title
Menstrual Blood Loss (MBL) as Measured by Pictorial Blood Loss Assessment Chart (PBLAC).
Description
The PBLAC is a simple, pictorial tool used in women with menorrhagia to assess menstrual blood loss. The total score is calculated by adding up the sum of all scores for the tampons or sanitary napkin used in the menstrual cycle. For tampons: 1 for lightly stained, 5 for moderately soiled and 10 for completely saturated tampons. For sanitary napkins: 1 for lightly stained, 5 for moderately soiled, and 20 for completely saturated pads. Clots were given a score of 1 for small and 5 for large clots. Abnormal PBLAC bleeding score greater than or equal to 100, which correlates with menorrhagia, defined as greater than 80 mL of menstrual blood loss. Normal bleeding is defined as a score of 75 or less. A score of 0 indicates amenorrhea, or absence of menstruation.
Time Frame
Measured at 12 months following initial treatment
Secondary Outcome Measure Information:
Title
Quality of Life Score Using the Short Form-12 (SF-12) Health Survey
Description
Quality of life (QoL) was measured by the SF-12 questionnaire. The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. Physical and Mental Health Composite Scores are computed (combined, scored, and weighted) using the scores of the 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. Improvement was defined as a change of ≥ 6 points.
Time Frame
Measured at 12 months following initial treatment
Title
Quality of Life as Measured by the Menorrhagia Multi-Attribute Scale (MMAS )
Description
The MMAS questionnaire captures the subjective consequences of menorrhagia on six domains: practical difficulties; social life; psychological wellbeing; physical health; work routine; and family life. Each of the six domains has four statements that represent four levels of response. Respondents indicate the statement that best matches their feelings for each domain. The statement scores derive from a weighting of the domains and a weighting of the statements in level of severity by women in the original study. Scores range from 0 (worst possible state in all domains) to 100 (best possible state in all domains).
Time Frame
Measured at 12 months following initial treatment
Title
Hemoglobin at 12 Months
Time Frame
Measured at 12 months following initial treatment
Title
Change in Hemoglobin
Time Frame
baseline, 12 months
Title
Ferritin at 12 Months
Time Frame
Measured at 12 months following initial treatment
Title
Change in Ferritin From Baseline
Time Frame
Measured at 12 months following initial treatment
Title
Direct Medical Costs
Description
Direct Medical Costs consisted of two categories: primarily hospital billed services, and primarily physician billed services. Primary hospital billed services were as defined by Medicare billing practice.
Time Frame
Measured at 12 months following initial treatment
Title
Indirect Medical Costs
Description
Indirect cost A refers to cost of sanitary products and lack of activity, indirect cost B refers to cost of sanitary products and reduced work days, and indirect cost C refers to cost of sanitary products, lack of activity, and reduced work days.
Time Frame
Measured at 12 months following initial treatment
Title
Bleeding Pattern at 12 Months
Description
The menstruation pattern of the subjects was evaluated. A bleeding episode was defined as any set of one or more bleeding days bounded at each end by two or more bleeding-free days. The bleeding pattern was analyzed using a 90 day reference period and divided into groups, (based on World Health Organization (WHO) classification of clinically important bleeding patterns). The groups are Amenorrhea (no bleeding during the reference period); Infrequent bleeding (fewer than 3 bleeding episodes); Irregular bleeding (between 3 and 5 episodes with less than 3 bleeding-free intervals of length 14 days or more); Prolonged bleeding (1 or more bleeding episodes lasting 14 days or more); Eumenorrhea "normal pattern" (none of the above patterns).
Time Frame
Measured at 12 months following initial treatment
Title
Pain at 12 Months as Measured by the Pain Visual Analog Scale (VAS)
Description
The pain VAS is a continuous scale comprised of a horizontal (HVAS) line, 100 mm in length. Possible scores range from 0 (no pain) to 100 (worst possible pain). The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks.
Time Frame
Measured at 12 months following initial treatment
Title
Subject Satisfaction at 12 Months
Description
Subject satisfaction was ascertained by asking study participants to choose from one of four categories relating to their general satisfaction with treatment: totally satisfied, generally satisfied, acceptable improvement in symptoms, or unacceptable treatment.
Time Frame
Measured at 12 months following initial treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult female, ages 30-55, who is pre-menopausal and for whom childbearing is complete Subjective symptom of excessive menstrual loss Normal uterine cavity length (≥ 4cm) with a sound measurement of ≤10cm documented by sonohysterogram or hysteroscopy in the preceding 6 months At least one normal Pap Test and no unexplained abnormal Pap Tests within 6 months of procedure Prior history of permanent sterilization or use of reliable non-hormonal contraception during the 14 month study period or history of vasectomy in partner Freely agree to participate in the study including all study related procedures and evaluations, and document this agreement by signing the informed consent document Exclusion Criteria: Pregnancy or desire for future childbearing Active lower genital infection at the time of procedure Active urinary tract infection at the time of procedure Active pelvic inflammatory disease (PID) or recurrent chronic PID Endometrial neoplasia, determined by endometrial biopsy taken within 12 months of study entry Current or past history of cervical or endometrial cancer Uterine sound measurement greater than 10cm Submucous leiomyoma greater than 2cm or cavity distorting leiomyoma History of myomectomy or classical cesarean section Previous endometrial ablation Oral hormonal treatment in the preceding 3 months, hormone releasing intrauterine contraceptive in the preceding month, or injectable hormone treatment in the preceding 12 months Contraindication to hormonal therapy and non-steroidal anti-inflammatory agents. History of a coagulopathy or endocrinopathy Inability to follow up at 12 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abimbola O. Famuyide, MBBS
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29141040
Citation
Famuyide AO, Laughlin-Tommaso SK, Shazly SA, Hall Long K, Breitkopf DM, Weaver AL, McGree ME, El-Nashar SA, Lemens MA, Hopkins MR. Medical therapy versus radiofrequency endometrial ablation in the initial treatment of heavy menstrual bleeding (iTOM Trial): A clinical and economic analysis. PLoS One. 2017 Nov 15;12(11):e0188176. doi: 10.1371/journal.pone.0188176. eCollection 2017.
Results Reference
derived

Learn more about this trial

Medical Therapy Versus Radiofrequency Endometrial Ablation in the Initial Treatment of Menorrhagia

We'll reach out to this number within 24 hrs