Minerva Pivotal Study to Evaluate Safety and Efficacy of the Aurora Endometrial Ablation System Compared to Hysteroscopic Rollerball Ablation

• Sponsor: Minerva Surgical, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01569763
• Collaborator: (none)
• Enrollment: 153
• Locations: 13
• Arms: 2
• Duration (Months): 72
• Patients Per Site: 11.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety and effectiveness of the Aurora Endometrial Ablation System as compared to hysteroscopic rollerball endometrial ablation in reducing menstrual blood loss at 12 months post-treatment.

Condition or Disease	Intervention/Treatment	Phase
Menorrhagia	Device: Aurora Endometrial Ablation; Device: Rollerball Ablation/Resection	N/A

Detailed Description

Menorrhagia is defined as menstrual bleeding in the ovulatory woman exceeding 80 ml per month. Approximately 20-25% of healthy premenopausal women have abnormal uterine bleeding. Menorrhagia can have a negative impact on a woman's lifestyle and self-perception, often leading her to seek definitive treatment. Pharmacologic treatment for menorrhagia is not always successful, and dilatation and curettage typically provides relief for only a few menstrual cycles. Traditionally hysterectomy has been the definitive treatment for menorrhagia. This clinical study evaluates the safety and effectiveness of the Aurora Endometrial Ablation System to provide a therapeutic treatment for menorrhagia due to benign causes by ablating the endometrial lining of the uterus in pre-menopausal women for whom childbearing is complete. Subjects who are randomized to the control group will receive hysteroscopic rollerball/resection ablation. Subjects randomized to the test arm will be treated with the Aurora Endometrial Ablation System.

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Minerva Pivotal Study
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Mar 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: hysteroscopic rollerball resection/ablation	Device: Rollerball Ablation/Resection; Hysteroscopic rollerball resection/ablation
Experimental: Aurora Endometrial Ablation	Device: Aurora Endometrial Ablation; Endometrial Ablation using the Aurora Endometrial Ablation system

Outcome Measures

Primary Outcome Measures

1. Reduction of Menstrual Bleeding to Normal or Below Normal at 12 Months [12 months]

   Clinical success was defined as a reduction in menstrual bleeding volume to ≤ 80 ml as measured by the alkaline hematin method (AH). Clinical success was not achieved if: (1) at one year post-treatment menstrual blood loss is greater than 80ml, as measured by AH; (2) an acute failure occurred (e.g., aborted procedure, etc.); or (3) the subject required additional therapy to control menorrhagia.

Secondary Outcome Measures

1. Procedure Time [< 1 hour]

   Procedure time is defined as the time from device insertion to time of device removal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Refractory menorrhagia with no definable organic cause

• Female subject from (and including) age 25 to 50 years

• Uterine sound measurement of no greater than10.0cm (external os to internal fundus) and a minimum uterine cavity length of 4.0cm

• A minimum menstrual blood loss of ≥ 160 ml for two baseline cycles within three months prior to treatment as measured by alkaline hematin extraction; OR,

• A minimum menstrual blood loss of ≥ 160 ml for one baseline cycle for women who either

• had at least 3 prior months documented failed medical therapy; or

• had a contraindication to medical therapy

• Premenopausal at enrollment as determined by FSH measurement ≤ 40 IU/L

• Not pregnant and no desire to conceive at any time

• Subject agrees to use a reliable form of contraception up to the 12-month follow-up visit. If a hormonal birth control method is used for contraception, the subject must have been on said method for ≥ 3 months prior to enrollment and agrees to remain on the same hormonal regimen through the initial 12-month follow-up

• Able to provide written informed consent using a form that has been approved by the reviewing IRB/EC

• Subject agrees to follow-up exams and data collection requirements

• Subject who is literate or demonstrates an understanding on how to collect menstrual blood loss products for the alkaline hematin method of analysis

Exclusion Criteria:

• Pregnancy or subject with a desire to conceive

• Endometrial hyperplasia as confirmed by histology

• Presence of 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, uterus or urinary tract at the time of the procedure

• Known/suspected abdominal pelvic or gynecological malignancy within the past 5 years

• Known clotting defects or bleeding disorders

• Untreated/unevaluated cervical dysplasia, except CIN I

• Prior uterine surgery (except low segment cesarean section) that interrupts the integrity of the uterine wall (e.g., transmural myomectomy or classical cesarean section)

• Previous endometrial ablation procedure

• Presence of an implantable (intrauterine) contraceptive device (e.g. Essure™ or Adiana™)

• Currently on medications that could thin the myometrial muscle, such as long-term steroid use (except inhaler or nasal therapy for asthma)

• Currently on anticoagulants

• Abnormal or obstructed cavity as confirmed by hysteroscopy, SIS or vaginal ultrasound

• Presence of an intrauterine device (IUD) which the Subject is unwilling to have removed at the time of the operative visit

• Subject currently on hormonal birth control therapy (including the Mirena device) for <3 months prior to enrollment

• Subject who is unwilling to use birth control post-ablation whether non-hormonal birth control or the same hormonal birth control therapy as before the procedure

• Subject who is within 6-weeks post partum

• Any subject who is currently participating or considers future participation in a research study of an investigational drug or device during the course of this investigational study

• Any general health condition which, in the opinion of the Investigator, could represent an increased risk for the subject

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Horizons Women's Care	Chandler	Arizona	United States	85224
2	Women's Health Research	Phoenix	Arizona	United States	85015
3	Basinski, LLC	Newburgh	Indiana	United States	47630
4	Cypress Medical Research Center, LLC	Wichita	Kansas	United States	67226
5	Minnesota Gynecology and Surgery	Edina	Minnesota	United States	55435
6	Mercy Clinic Minimally Invasive Gynecology	Saint Louis	Missouri	United States	63141
7	Tennessee Women's Care PC	Nashville	Tennessee	United States	37203
8	Baylor Research Institute	Fort Worth	Texas	United States	76104
9	McMaster University/Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N3Z5
10	Hôpital LaSalle	Ville Lassalle	Quebec	Canada	H8P 1C1
11	Regina Qu'Appelle Health Region	Regina	Saskatchewan	Canada	S4S 6X3
12	La Cite Medicale	Quebec		Canada	G1W 2J5
13	Hospital Universitario, UANL	Monterrey	Nuevo Leon	Mexico	64460

Sponsors and Collaborators

• Minerva Surgical, Inc.

Investigators

• Study Director: Eugene Skalnyi, MD, Minerva Surgical, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Minerva Surgical, Inc.
• ClinicalTrials.gov Identifier: NCT01569763
• Other Study ID Numbers: CIP0005
• First Posted: Apr 3, 2012
• Last Update Posted: Apr 18, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Minerva Surgical, Inc.: endometrial ablation
• Additional relevant MeSH terms: Menorrhagia

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled in the clinical trial at 13 Investigational Sites in the U.S., Canada, and Mexico between March 2012 until November 2013.
Pre-assignment Detail	A total of 153 subjects were enrolled and randomized 2:1 to the Minerva (Aurora) Test Group (n=102) or the Rollerball Control Group (n=51). As part of the randomization process, subjects were stratified by age, though there was no attempt to enroll an equal number into the < 40 and > 40 age groups. All 153 subjects were successfully treated.

Arm/Group Title	Aurora Endometrial Ablation	Hysteroscopic Rollerball Resection/Ablation
Arm/Group Description	Aurora Endometrial Ablation: Endometrial Ablation using the Aurora Endometrial Ablation system	Rollerball Ablation/Resection: Hysteroscopic rollerball resection/ablation
Period Title: Overall Study
STARTED	102	51
Treated	102	51
COMPLETED	99	44
NOT COMPLETED	3	7

Baseline Characteristics

Arm/Group Title	Aurora Endometrial Ablation	Hysteroscopic Rollerball Resection/Ablation	Total
Arm/Group Description	Aurora Endometrial Ablation: Endometrial Ablation using the Minerva Endometrial Ablation system	Rollerball Ablation/Resection: Hysteroscopic rollerball resection/ablation	Total of all reporting groups
Overall Participants	102	51	153
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.6 (4.2)	42.5 (4.7)	42.5 (4.4)
Sex: Female, Male (Count of Participants)
Female	102 100%	51 100%	153 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	54 52.9%	26 51%	80 52.3%
United States	20 19.6%	12 23.5%	32 20.9%
Mexico	28 27.5%	13 25.5%	41 26.8%
Alkaline Hematin Value at Baseline (Menstrual Blood Loss (ml)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Menstrual Blood Loss (ml)]	310.2 (169.0)	301.8 (176.1)	307.4 (170.9)

Outcome Measures

1. Primary Outcome

Title	Reduction of Menstrual Bleeding to Normal or Below Normal at 12 Months
Description	Clinical success was defined as a reduction in menstrual bleeding volume to ≤ 80 ml as measured by the alkaline hematin method (AH). Clinical success was not achieved if: (1) at one year post-treatment menstrual blood loss is greater than 80ml, as measured by AH; (2) an acute failure occurred (e.g., aborted procedure, etc.); or (3) the subject required additional therapy to control menorrhagia.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All Randomized subjects in whom treatment was attempted

Arm/Group Title	Aurora Endometrial Ablation	Hysteroscopic Rollerball Resection/Ablation
Arm/Group Description	Aurora Endometrial Ablation: Endometrial Ablation using the Aurora Endometrial Ablation system	Rollerball Ablation/Resection: Hysteroscopic rollerball resection/ablation
Measure Participants	102	51
Number [participants]	95 93.1%	41 80.4%

2. Secondary Outcome

Title	Procedure Time
Description	Procedure time is defined as the time from device insertion to time of device removal.
Time Frame	< 1 hour

Outcome Measure Data

Analysis Population Description

Subjects completing treatment

Arm/Group Title	Aurora Endometrial Ablation	Hysteroscopic Rollerball Resection/Ablation
Arm/Group Description	Aurora Endometrial Ablation: Endometrial Ablation using the Aurora Endometrial Ablation system	Rollerball Ablation/Resection: Hysteroscopic rollerball resection/ablation
Measure Participants	102	51
Mean (Standard Deviation) [Minutes]	3.1 (0.5)	17.2 (6.7)

3. Post-Hoc Outcome

Title	Subjects With Amenorrhea at 12 Months
Description	Amenorrhea at 12 Months- Number of Subjects experiencing no menstrual bleeding
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Randomized subjects

Arm/Group Title	Aurora Endometrial Ablation	Hysteroscopic Rollerball Resection/Ablation
Arm/Group Description	Aurora Endometrial Ablation: Endometrial Ablation using the Aurora Endometrial Ablation system	Rollerball Ablation/Resection: Hysteroscopic rollerball resection/ablation
Measure Participants	102	51
Number [participants]	73 71.6%	25 49%

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	All Serious Adverse Events observed during the clinical study, regardless of relationship to the study device or procedure are reported below. All non-Serious Adverse Events considered possibly, probably or highly probably related to the device or procedure are reported below.
Arm/Group Title	Aurora Endometrial Ablation		Hysteroscopic Rollerball Resection/Ablation
Arm/Group Description	Aurora Endometrial Ablation: Endometrial Ablation using the Aurora Endometrial Ablation system		Rollerball Ablation/Resection: Hysteroscopic rollerball resection/ablation
All Cause Mortality
	Aurora Endometrial Ablation		Hysteroscopic Rollerball Resection/Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aurora Endometrial Ablation		Hysteroscopic Rollerball Resection/Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/102 (4.9%)		3/51 (5.9%)
Endocrine disorders
Thyroid Nodule	1/102 (1%)	1	0/51 (0%)	0
Metabolism and nutrition disorders
Hyponatremia	1/102 (1%)	1	0/51 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myeloma	1/102 (1%)	1	0/51 (0%)	0
Reproductive system and breast disorders
Bleeding	0/102 (0%)	0	1/51 (2%)	1
Endometritis	0/102 (0%)	0	1/51 (2%)	1
Pelvic Inflammatory Disease (PID)	1/102 (1%)	1	0/51 (0%)	0
Continued Heavy Menstrual Bleeding	0/102 (0%)	0	1/51 (2%)	1
Surgical and medical procedures
Anesthesia Related	1/102 (1%)	1	0/51 (0%)	0
Other (Not Including Serious) Adverse Events
	Aurora Endometrial Ablation		Hysteroscopic Rollerball Resection/Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/102 (13.7%)		10/51 (19.6%)
Gastrointestinal disorders
Nausea and/or Vomiting	0/102 (0%)	0	1/51 (2%)	1
Abdominal Pain and/or Bloating	3/102 (2.9%)	3	2/51 (3.9%)	2
Constipation	0/102 (0%)	0	1/51 (2%)	1
General disorders
Weaknes, Fatigue, Sleepiness, Lack of concentration, Dizziness	2/102 (2%)	2	1/51 (2%)	1
Musculoskeletal and connective tissue disorders
Backache	1/102 (1%)	1	0/51 (0%)	0
Reproductive system and breast disorders
Bleeding or spotting	0/102 (0%)	0	1/51 (2%)	1
Pelvic Pain	1/102 (1%)	1	0/51 (0%)	0
Vaginal discharge, unpleasant smell, burning, abnormal sensation	1/102 (1%)	1	0/51 (0%)	0
Endometritis or Endomyometritis	1/102 (1%)	1	2/51 (3.9%)	2
Pelvic Inflammatory Disease (PID)	1/102 (1%)	1	0/51 (0%)	0
Hematometra	1/102 (1%)	1	0/51 (0%)	0
Dysmenorrhea	0/102 (0%)	0	1/51 (2%)	1
Skin and subcutaneous tissue disorders
Skin Rash and/or Itching or Burning Sensation	2/102 (2%)	2	1/51 (2%)	1
Surgical and medical procedures
Fever	1/102 (1%)	1	0/51 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator has the right to publish their research for non-profit and academic purposes, provided the 1st publication of results shall be in conjunction with results from all centers in this Study. If Investigator desires to publish/present data obtained by Investigator, following completion of the Study at all sites, Investigator may do so, provided a copy of proposed publication/presentation is received by Company for review/comment at least 15 days in advance of submission for publication.