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

Phase 4

Completed

Conditions: Menorrhagia

Interventions: Drug: Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills
Device: NovaSure® Radiofrequency Endometrial Ablation
Drug: Naproxen sodium pills

Registration Number: NCT01165307

Lead Sponsor: Abimbola Famuyide

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 77

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Medical Therapy	Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills	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).
Medical Therapy	Naproxen sodium pills	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).
Radiofrequency Endometrial Ablation	NovaSure® Radiofrequency Endometrial Ablation	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.

Primary Outcome Measures

Name	Time	Method
Menstrual Blood Loss (MBL) as Measured by Pictorial Blood Loss Assessment Chart (PBLAC).	Measured at 12 months following initial treatment	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

Name	Time	Method
Quality of Life Score Using the Short Form-12 (SF-12) Health Survey	Measured at 12 months following initial treatment	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 )	Measured at 12 months following initial treatment	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	Measured at 12 months following initial treatment
Change in Hemoglobin	baseline, 12 months
Ferritin at 12 Months	Measured at 12 months following initial treatment
Change in Ferritin From Baseline	Measured at 12 months following initial treatment
Direct Medical Costs	Measured at 12 months following initial treatment	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	Measured at 12 months following initial treatment	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	Measured at 12 months following initial treatment	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)	Measured at 12 months following initial treatment	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	Measured at 12 months following initial treatment	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.