Safety Study of ExAblate for the Treatment of Uterine Fibroids

• Sponsor: InSightec (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01142791
• Collaborator: (none)
• Enrollment: 121
• Locations: 8
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 15.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The objective of this Phase IV study is to evaluate the safety of the ExAblate treatment of uterine fibroids using the enhanced sonication techniques, based on the current commercially-approved treatment guidelines. Treatment may include up to 100% of individual fibroid volume, within established serosal and sacral treatment margins.

The Enhanced sonication is one of the various sonication modes that may lead to increased thermal dose volume of each sonication without additional safety risks. This is an additional treatment tool available in the ExAblate system for the treatment of uterine fibroids.

The safety profile of the Enhanced Sonication was investigated under an FDA-regulated IDE study. FDA granted approval of Enhanced Sonication with the requirement to perform a post-approval study to collect additional safety data when treating up to 100% of individual fibroid volume.

Condition or Disease	Intervention/Treatment	Phase
Uterine Fibroids	Device: ExAblate	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV Clinical Study To Evaluate the Safety of MR-Guided Focused Ultrasound Treatment of Uterine Fibroids With Enhanced Sonication Techniques
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: ExAblate treatment	Device: ExAblate; Magnetic resonance image-guided focused ultrasound (MRgFUS) for fibroid ablation

Outcome Measures

Primary Outcome Measures

1. Percent Occurrence of Chronic Leg Pain [From treatment to 1-month post-treatment]

   The hypothesis was that over 90% of subjects would not experience chronic leg pain. A lower 95% Confidence Limit > 0.90 was considered statistically successful.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women age 18 or older

• Symptomatic uterine fibroids, defined as those resulting in scores of 21 or higher, based on patient responses to questions 1-8 of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)

• Women who have given written informed consent

• Women who are able and willing to attend all study visits.

• Patient is pre or peri-menopausal (within 12 months of last menstrual period).

• Patient should be family complete.

• Able to communicate sensations during the ExAblate procedure.

• Uterine fibroids, which are device accessible (i.e., positioned in the uterus such that they can be accessed without being shielded by bowel or bone).

• Fibroids(s) clearly visible on non-contrast MRI.

• Fibroid enhances on MR contrast imaging.

Exclusion Criteria:

• Women who are pregnant, as confirmed by serum/urine test at time of screening, or urine pregnancy test on the day of treatment.

• Patients who are breast-feeding.

• Patients with active pelvic inflammatory disease (PID).

• Patients with active local or systemic infection.

• Patients experiencing chronic leg or lower back pain within the last 6 months.

• Contraindication for MRI Scan:

• Severe claustrophobia that would prevent completion of procedure in the MR unit

• Weight greater than 250 lbs (113Kg)

• Implanted ferromagnetic materials and/or devices contraindicated for MR scan

• Known intolerance to MRI contrast agent (e.g. Gadolinium or Magnevist)

• Any other contraindication for MRI Scan

• Extensive abdominal scarring in the beam path (that cannot be avoided by redirection of the beam).

• Dermoid cyst of the ovary anywhere in the treatment path.

• Known or suspected pelvic carcinoma or pre-malignant conditions, including sarcoma and adenomatous hyperplasia.

• Intrauterine device (IUD) anywhere in the treatment path.

• Undiagnosed vaginal bleeding.

• Pedunculated fibroids.

• Uterine size >24 weeks.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095
2	UCSD Department of Radiology	San Diego	California	United States	92103-8749
3	University of California San Francisco	San Francisco	California	United States	94107
4	University Image Guided Therapy	Boca Raton	Florida	United States	33431
5	Borgess Research Institute	Kalamazoo	Michigan	United States	49048
6	Duke University	Durham	North Carolina	United States	27705
7	The Methodist Hospital Research Institute	Houston	Texas	United States	77030
8	University of Virginia Health System	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• InSightec

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Sponsor's Web Page

Publications

None provided.

• Responsible Party: InSightec
• ClinicalTrials.gov Identifier: NCT01142791
• Other Study ID Numbers: UF033
• First Posted: Jun 11, 2010
• Last Update Posted: Mar 19, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by InSightec: Uterine fibroids; MRgFUS; ExAblate; Focused Ultrasound; Symptomatic uterine fibroids
• Additional relevant MeSH terms: Leiomyoma; Myofibroma

Study Results

Participant Flow

Pre-assignment Detail	The protocol defined the primary analysis to include participants receiving more than 1 sonication, i.e., 115 in this case. The safety population was defined in the protocol as participants receiving any sonications which is 121. 6 subjects receiving only 1 sonication were in the safety population but not in the baseline or primary analysis.

Arm/Group Title	ExAblate Treatment	Additional Safety Population Particpants
Arm/Group Description	ExAblate: Magnetic resonance image-guided focused ultrasound (MRgFUS) for fibroid ablation. Phase IV enhanced sonication technique.	Per protocol 6 participants receiving only 1 sonication were added to the 115 ExAblate treated subjects to compose the full safety analysis population of 121. These 6 were included in adverse event reporting only, not in baseline or efficacy analyses.
Period Title: Overall Study
STARTED	115	6
Safety	115	6
COMPLETED	108	0
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	ExAblate Treatment
Arm/Group Description	ExAblate: Magnetic resonance image-guided focused ultrasound (MRgFUS) for fibroid ablation
Overall Participants	115
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (5.6)
Sex: Female, Male (Count of Participants)
Female	115 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
European/Middle East (White)	84 73%
Hispanic	6 5.2%
Black	14 12.2%
Asian	8 7%
Other	3 2.6%
Region of Enrollment (participants) [Number]
United States	115 100%

Outcome Measures

1. Primary Outcome

Title	Percent Occurrence of Chronic Leg Pain
Description	The hypothesis was that over 90% of subjects would not experience chronic leg pain. A lower 95% Confidence Limit > 0.90 was considered statistically successful.
Time Frame	From treatment to 1-month post-treatment

Outcome Measure Data

Analysis Population Description

Per protocol the number of participants analyzed was the number of participants receiving more than one sonication. Six subjects receiving one sonication were excluded from the primary analysis but included in the safety population for a safety sample size n = 121.

Arm/Group Title	ExAblate Treatment
Arm/Group Description	ExAblate: Magnetic resonance image-guided focused ultrasound (MRgFUS) for fibroid ablation. Phase IV enhanced sonication technique.
Measure Participants	115
Number (95% Confidence Interval) [percentage of subjects without leg pain]	97

Adverse Events

Time Frame	1 Month
Adverse Event Reporting Description	Per protocol a predetermined sample size of 115 participants receiving more than one sonication were included in the primary analysis. An additional 6 subjects receiving a single sonication were excluded from the primary analysis but included in the adverse events analysis for a safety sample size of 121.
Arm/Group Title	ExAblate Treatment
Arm/Group Description	ExAblate: Magnetic resonance image-guided focused ultrasound (MRgFUS) for fibroid ablation. Phase IV enhanced sonication technique.
All Cause Mortality
	ExAblate Treatment
	Affected / at Risk (%)	# Events
Total	0/121 (0%)
Serious Adverse Events
	ExAblate Treatment
	Affected / at Risk (%)	# Events
Total	0/121 (0%)
Other (Not Including Serious) Adverse Events
	ExAblate Treatment
	Affected / at Risk (%)	# Events
Total	105/121 (86.8%)
Gastrointestinal disorders
Abdominal distension	1/121 (0.8%)	1
Bloating abdomen	1/121 (0.8%)	1
Constipation	5/121 (4.1%)	5
Diarrhea	1/121 (0.8%)	1
GI upset	1/121 (0.8%)	1
Heartburn	2/121 (1.7%)	2
Nausea/vomiting	11/121 (9.1%)	12
General disorders
Cramping abdomen	2/121 (1.7%)	2
Cramping back/buttock/leg	1/121 (0.8%)	1
Tenderness abdomen	3/121 (2.5%)	3
Fatigue	1/121 (0.8%)	1
Fever	4/121 (3.3%)	4
Flu	1/121 (0.8%)	1
Medication error	1/121 (0.8%)	1
Insomnia	1/121 (0.8%)	1
Musculoskeletal and connective tissue disorders
Mass - fat necrosis	1/121 (0.8%)	1
Cramping position related	1/121 (0.8%)	1
Cramping muscle leg	1/121 (0.8%)	1
Pain neck/shoulder position related	3/121 (2.5%)	4
Pubic bone soreness position related	1/121 (0.8%)	1
Cramping muscle inguinal	1/121 (0.8%)	1
Pain lower extremity position related	14/121 (11.6%)	15
Discomfort neck/shoulder position related	1/121 (0.8%)	1
Tenderness abdomen position related	1/121 (0.8%)	1
Nervous system disorders
Parasthesia	2/121 (1.7%)	2
Renal and urinary disorders
Dysuria	2/121 (1.7%)	2
Hematuria	2/121 (1.7%)	2
Infection bladder	1/121 (0.8%)	1
Urinary tract infection	3/121 (2.5%)	3
Cystitis	1/121 (0.8%)	1
Reproductive system and breast disorders
Edema/swelling abdome	3/121 (2.5%)	4
Amennorhia	1/121 (0.8%)	1
Cramping menstrual	6/121 (5%)	6
Vaginal discharge/bleeding	7/121 (5.8%)	7
Skin and subcutaneous tissue disorders
Erythema abdomen	1/121 (0.8%)	1
Infection IV site	1/121 (0.8%)	1
Skin burn	5/121 (4.1%)	5
Surgical and medical procedures
Skin pain sonication relaed	54/121 (44.6%)	67
Cramping Sonication related	12/121 (9.9%)	12
Pain uterine sonication related	2/121 (1.7%)	2
Discomfort back/buttock/leg sonication related	1/121 (0.8%)	1
Pain abdomen sonication related	63/121 (52.1%)	78
Pain back/buttock/leg sonication related	70/121 (57.9%)	104
Vascular disorders
Increased blood pressure	1/121 (0.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.