Clinical trial NCT02736435: Treatment of Uterine Fibroids With Magnetic Resonance Guided High Intensity Focused Ultrasound
Official title: Treatment of Uterine Fibroids With Magnetic Resonance Guided High Intensity Focused Ultrasound
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Uterine Leiomyoma
Keywords: Magnetic Resonance Guided High Intensity Focused Ultrasound
MR-HIFU
Fibroids
Leuprolide Acetate
Lead sponsor: Thunder Bay Regional Health Research Institute
Sponsor class: OTHER
First posted: 2016-04-13
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate the effectiveness of MR-HIFU for the treatment of uterine fibroids in Northwestern Ontario, which is a rural and remote setting.

Detailed description: Uterine fibroids are benign smooth muscle tumours of the muscular wall of the uterus that affect 40 per cent of women. While the majority of fibroids are asymptomatic, fibroids may cause menorrhagia, bulk symptoms (i.e. ureteric obstruction, urinary frequency and urgency, bowel dysfunction), pain and in certain instances infertility.

Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) treatment of fibroids is an established method for symptom alleviation with over 3000 women receiving treatment worldwide. MR-HIFU is a non-invasive, non-surgical procedure that uses ultrasound energy to thermally ablate the fibroid leading to a reduction in bleeding and in the size of uterine fibroids over time. MR-HIFU it is not currently being used for the treatment of symptomatic fibroids in Canada.

The Thunder Bay Regional Research Institute has one of the first clinically available MR-HIFU equipment in Canada. In order to bring this technology into clinical practice, a knowledge translation study is needed to demonstrate that MR-HIFU can treat symptomatic uterine fibroids as successfully in Northwestern Ontario compared to urban centres where all of the clinical trials have been conducted. The ability to screen and follow up women treated with MR-HIFU with ultrasound rather than MRI would allow participants to receive follow up in regional centres in Northwestern Ontario and it would be more cost effective from a health system perspective. In addition, more research is needed to broaden the scope of treatment to include fibroids greater than 8 cm such that more women could benefit from this non-surgical fibroid management option.

Eligibility criteria: Inclusion Criteria:

* Women aged 18 to 50 years
* Weight \<140kg
* Pre or perimenopausal
* Uterine size \<24 weeks
* Cervical screen by Pap test: Normal, Low Grade Squamous Intraepithelial Lesion, or Atypical Squamous Cells of Undetermined Significance as per Cancer Care Ontario guidelines
* Transformed symptom severity score ≥40
* Willing to attend all study visits
* Willing to complete evaluation forms
* Willing and able to use reliable contraception;

MR-HIFU Criteria Trial Arm 1:

* Minimum of 50% of fibroid volume accessible for treatment
* Dominant fibroid ≤8 cm
* Uterine volume \<900 cc
* Total fibroid treatment volume \<250 cc
* No more than 5 fibroids planned for ablation
* Completely non-enhancing fibroids should not be treated

MR-HIFU Criteria Trial Arm 2:

* Minimum of 50% of fibroid volume accessible for treatment
* Dominant fibroid \>8 cm or uterine volume \>900 cc
* Total fibroid treatment volume \<250 cc
* No more than 5 fibroids planned for ablation
* Completely non-enhancing fibroids should not be treated

Exclusion Criteria:

* Other pelvic disease (endometriosis, ovarian tumor, acute pelvic disease, other mass)
* Significant systemic disease even if well controlled
* Positive pregnancy test
* Abnormal uterine bleeding (participant can be included if an endometrial biopsy confirms no hyperplasia or malignancy in the past 6 months)
* Extensive scarring along anterior abdominal wall (\>50% of area)
* Surgical clips or scar tissue in the path of the MR-HIFU beam
* MRI contraindicated according to standard operating procedure
* MRI contrast contraindicated (including renal insufficiency)
* Calcifications around or throughout uterine tissues
* Fibroids not quantifiable on MRI
* Highly perfused or brighter than myometrium in T2-weighted MRI fibroids (Type 3 fibroids).

Primary outcomes:
measure: Change in uterine fibroid symptom severity scale
timeFrame: 3, 6, and 12 months
Secondary outcomes:
measure: Change in short form McGill pain questionnaire
timeFrame: 24h, 72h, 6week, 3, 6, and 12 month
measure: Change in pictorial blood loss assessment chart
timeFrame: 3, 6, and 12 months
measure: Change in uterine fibroid symptom and health-related quality of life questionnaire
timeFrame: 12 months
measure: Participant use of alternative therapies for treatment of fibroids
timeFrame: 6 weeks, 3, 6, and 12 months
measure: MR Imaging to assess change in fibroid volume.
timeFrame: 3, 6, and 12 months
measure: MR Imaging to assess change in perfusion.
timeFrame: 3, 6, and 12 months
measure: Ultrasound imaging to assess change in fibroid volume.
timeFrame: 3, 6, and 12 months
measure: Ultrasound imaging to assess change in fibroid perfusion.
timeFrame: 3, 6, and 12 months
Other outcomes:
measure: Return to activity within 72 hours of treatment
timeFrame: 72 hours
measure: Change in hemoglobin level
timeFrame: 3, 6, and 12 months
Locations:
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
Study officials:
affiliation: Northern Ontario School of Medicine, Thunder Bay Regional Research Institute
name: Naana A Jumah, MD DPhil FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Friedman AJ, Hoffman DI, Comite F, Browneller RW, Miller JD. Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. Obstet Gynecol. 1991 May;77(5):720-5.
citation: Gizzo S, Saccardi C, Patrelli TS, Ancona E, Noventa M, Fagherazzi S, Mozzanega B, D'Antona D, Nardelli GB. Magnetic resonance-guided focused ultrasound myomectomy: safety, efficacy, subsequent fertility and quality-of-life improvements, a systematic review. Reprod Sci. 2014 Apr;21(4):465-76. doi: 10.1177/1933719113497289. Epub 2013 Jul 18.
citation: Quinn SD, Vedelago J, Gedroyc W, Regan L. Safety and five-year re-intervention following magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids. Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:247-51. doi: 10.1016/j.ejogrb.2014.09.039. Epub 2014 Oct 6.
citation: Smart OC, Hindley JT, Regan L, Gedroyc WG. Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata. Obstet Gynecol. 2006 Jul;108(1):49-54. doi: 10.1097/01.AOG.0000222381.94325.4f.
citation: Stewart EA, Gostout B, Rabinovici J, Kim HS, Regan L, Tempany CM. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol. 2007 Aug;110(2 Pt 1):279-87. doi: 10.1097/01.AOG.0000275283.39475.f6.
citation: Thiburce AC, Frulio N, Hocquelet A, Maire F, Salut C, Balageas P, Bouzgarrou M, Hocke C, Trillaud H. Magnetic resonance-guided high-intensity focused ultrasound for uterine fibroids: Mid-term outcomes of 36 patients treated with the Sonalleve system. Int J Hyperthermia. 2015;31(7):764-70. doi: 10.3109/02656736.2015.1063169. Epub 2015 Sep 14.