Pilot Study of MRI-Guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids
Study Details
Study Description
Brief Summary
Uterine fibroids (leiomyomas) are a common cause of heavy uterine bleeding and pain in reproductive aged women and are the most common cause of hysterectomy in the United States. Women are seeking new ways to treat symptomatic uterine fibroids that allow them to avoid surgery. This study is the first step in this quest. We will study the novel use of magnetic resonance imaging (MRI) in enhancing the safety of the FDA approved technique to treat fibroids called High Intensity Focused Ultrasound (HIFU). The term 'high intensity focused ultrasound' means using ultrasound to heat and to thermally destroy tissue, in this case, uterine fibroids. The MRI system will allow us to watch the ultrasound path during treatment and monitor the temperature increase in the fibroid tissue that comes during the procedure.
In this pilot study, women with symptomatic fibroids will undergo MRI guided HIFU and then have a hysterectomy. This will allow us to confirm studies done in animals which show that it is possible to destroy specific tissue without harming normal tissue surrounding the targeted area.
The purpose of this clinical study is to confirm the safety and treatment capabilities of the Philips MR guided HIFU system for ablation of uterine fibroids. This is a single arm pilot study of 10 women who will undergo hysterectomy after the HIFU procedure. This study design of hysterectomy after treatment has been requested by the FDA as part of IDE approval for this new device and mirrors what has been required for similar devices. Safety will be assessed by evaluating treatment accuracy, complications, and adverse events. Treatment capabilities will be assessed by evaluating the fibroid volume ablated and other factors related to the procedure feasibility and acceptance including procedure duration, time to return to normal activity, and pain scores at the time of the procedure.
Study population
The Philips MR-HIFU System is intended for ablation of uterine fibroid tissue in pre- or perimenopausal women with symptomatic uterine fibroids who desire a uterine-sparing procedure. Patients must have completed child bearing prior to enrolling in this study. Patients will be recruited by referral to gynecology and interventional radiology at the NIH Clinical Center. Candidates for enrollment will already have symptomatic uterine leiomyomas and be willing to undergo hysterectomy for treatment. It is estimated that of apparently eligible subjects, at least 30 women will have to be screened in person in order to identify 10 who will be eligible for this study. Other studies of fibroid treatments are currently ongoing at the NIH. Women who have been interested in, but have not been selected for enrollment in those studies and who appear to be eligible to this study will be contacted for potential enrollment.
Study design:
This study is a multi-center, single arm trial evaluating the safety and treatment capabilities of the Philips MR-guided HIFU system in the treatment of symptomatic uterine fibroid patients who are otherwise healthy women. All patients enrolled in the study will undergo hysterectomy within a window of 30 days following HIFU treatment. Patients who have symptomatic uterine fibroids, meet clinical indications for hysterectomy, are eligible according to the inclusion and exclusion criteria and provide informed consent will be enrolled in this study. This study design of treatment followed by hysterectomy has been requested by the FDA as part of IDE approval for this new device and mirrors what has been required for similar devices. It is anticipated that women will participate in the study for a 3 month period to include the screening, HIFU treatment, hysterectomy and post hysterectomy follow-up.
The methodology used for this HIFU device capitalizes on the thermal properties of volumetric ablation rather than point ablation used by other focused ultrasound systems. Thus it is anticipated that this device will have a shorter treatment time compared to other HIFU machines. This HIFU system, via real-time MR thermometry monitoring, has automated thermal feedback during the procedure which may enhance safety. This pilot study will not only assess the safety of this device but will enable us to delineate the treatment capabilities of this system for future use in patients who want uterine sparing non-surgical treatment for symptomatic fibroids.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Uterine fibroids (leiomyomas) are a common cause of heavy uterine bleeding and pain in reproductive aged women and are the most common cause of hysterectomy in the United States. Women are seeking new ways to treat symptomatic uterine fibroids that allow them to avoid surgery. This study is the first step in this quest. We will study the novel use of magnetic resonance imaging (MRI) in enhancing the safety of the FDA approved technique to treat fibroids called High Intensity Focused Ultrasound (HIFU). The term high intensity focused ultrasound means using ultrasound to heat and to thermally destroy tissue, in this case, uterine fibroids. The MRI system will allow us to watch the ultrasound path during treatment and monitor the temperature increase in the fibroid tissue that comes during the procedure.
In this pilot study, women with symptomatic fibroids will undergo MRI guided HIFU and then have a hysterectomy. This will allow us to confirm studies done in animals which show that it is possible to destroy specific tissue without harming normal tissue surrounding the targeted area.
The purpose of this clinical study is to confirm the safety and treatment capabilities of the Philips MR guided HIFU system for ablation of uterine fibroids. This is a single arm pilot study of 10 women who will undergo hysterectomy after the HIFU procedure. This study design of hysterectomy after treatment has been requested by the FDA as part of IDE approval for this new device and mirrors what has been required for similar devices. Safety will be assessed by evaluating treatment accuracy, complications, and adverse events. Treatment capabilities will be assessed by evaluating the fibroid volume ablated and other factors related to the procedure feasibility and acceptance including procedure duration, time to return to normal activity, and pain scores at the time of the procedure.
Study population
The Philips MR-HIFU System is intended for ablation of uterine fibroid tissue in pre- or perimenopausal women with symptomatic uterine fibroids who desire a uterine-sparing procedure. Patients must have completed child bearing prior to enrolling in this study. Patients will be recruited by referral to gynecology and interventional radiology at the NIH Clinical Center. Candidates for enrollment will already have symptomatic uterine leiomyomas and be willing to undergo hysterectomy for treatment. It is estimated that of apparently eligible subjects, at least 30 women will have to be screened in person in order to identify 10 who will be eligible for this study. Other studies of fibroid treatments are currently ongoing at the NIH. Women who have been interested in, but have not been selected for enrollment in those studies and who appear to be eligible to this study will be contacted for potential enrollment.
Study design:
This study is a multi-center, single arm trial evaluating the safety and treatment capabilities of the Philips MR-guided HIFU system in the treatment of symptomatic uterine fibroid patients who are otherwise healthy women. All patients enrolled in the study will undergo hysterectomy within a window of 30 days following HIFU treatment. Patients who have symptomatic uterine fibroids, meet clinical indications for hysterectomy, are eligible according to the inclusion and exclusion criteria and provide informed consent will be enrolled in this study. This study design of treatment followed by hysterectomy has been requested by the FDA as part of IDE approval for this new device and mirrors what has been required for similar devices. It is anticipated that women will participate in the study for a 3 month period to include the screening, HIFU treatment, hysterectomy and post hysterectomy follow-up.
The methodology used for this HIFU device capitalizes on the thermal properties of volumetric ablation rather than point ablation used by other focused ultrasound systems. Thus it is anticipated that this device will have a shorter treatment time compared to other HIFU machines. This HIFU system, via real-time MR thermometry monitoring, has automated thermal feedback during the procedure which may enhance safety. This pilot study will not only assess the safety of this device but will enable us to delineate the treatment capabilities of this system for future use in patients who want uterine sparing non-surgical treatment for symptomatic fibroids.
Primary Outcome parameters:
-
Verifying with MR imaging that the location of the HIFU lesion matches the expected location (binary)
-
Verifying with MR imaging that no unintended lesions are formed as a result of the treatment (binary)
-
Examining the uterine capsule and surrounding areas for unintended damage during hysterectomy (binary)
-
Evaluating any complications or adverse events that result from the MR-guided HIFU treatment (categorical)
-
Comparing the actual MR-measured ablated volumes to MR thermal dose predicted volumes (categorical)
-
Comparing the ablated volumes from histology to MR thermal dose predicated volume (categorical)
-
Ensuring on histopathologic examination of the uterus that the zones treated by MR-guided HIFU treatment are indeed necrosed (binary)
Secondary Outcome Parameters:
-
Pain and discomfort scores immediately before, during and after HIFU treatment:
-
Length of Hospital Stay (LOS)
-
Return to Activity
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Philips MR guided HIFU system Patient receiving HIFU treatment |
Device: Philips MR guided HIFU system
HIFU is the use of focused ultrasound energy to penetrate through soft tissue and causes localized high temperatures (55°C to 70°C) for a few seconds within the target producing well defined regions of protein denaturation, irreversible cell damage, and coagulative necrosis
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Treatment-related Adverse Events (AE) Per Subject Resulting From HIFU Treatment of the Uterine Fibroids [end of follow-up (date of hysterectomy, at latest day 30 after treatment)]
The number of treatment-related Adverse Events (AE) reported during the study, divided by the total number of treated subjects. This corresponds to the mean number of treatment-related Adverse Events per subject. Relatedness of an AE to the treatment was judged case-by-case by the investigator.
Secondary Outcome Measures
- HIFU Treatment Equals Location Per Hysterectomy [Day 0, Hysterectomy]
Count the number of participants in which both of the following conditions are satisfied: the fibroid treated area as shown on MRI images during treatment is the same as displayed on fibroids from histology slices after hysterectomy, and no unintended lesions are visible in the uterus.
- Length of Time to Return to Normal Activities [end of follow-up (date of hysterectomy, at latest day 30 after treatment)]]
Length of time to return to normal activity measured in number of days from HIFU treatment. Assessed by patient interviews during follow-up.
- Numerical Range Scale (NRS) of Pain Level [Treatment Day: Baseline, Recovery, Discharge; Follow-up: 24 hours, 48 hours, 72 hours, 1 week, 2 weeks]
Pain Scores obtained by patient self-assessment on a 0-10 scale, with 0 corresponding to no pain and 10 corresponding to maximum pain.
- Discomfort Level [Treatment Day: Baseline, Recovery, Discharge; Follow-up: 24 hours, 48 hours, 72 hours, 1 week, 2 weeks]
Patient's self-assessed discomfort level on a 4-point scale, with: 0 = no pain; 1 = mild; 2 = moderate; 3 = severe.
Eligibility Criteria
Criteria
- INCLUSION CRITERIA:
-
Recommended for Total Abdominal Hysterectomy
-
Age between 18 and 59
-
Weight less than 140kg (or 310lbs)
-
Pre or peri menopausal with FSH less than 40 mIU/ml
-
Uterine size less than 24 weeks based on MRI and physical exam assessment
-
Symptom severity score greater than or equal to 50 by Spies Uterine Fibroid Questionnaire.
-
Cervical cytology no more severe than low grade SIL
-
History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the ACOG practice bulletin (ACOG Practice Bulletin 1994):
-
Dominant intramural fibroid greater than or equal to 3 cm and less than or equal to 16 cm on imaging.
EXCLUSION CRITERIA:
-
Other pelvic disease (mass indicated by history or MR imaging such as endometriosis, ovarian tumor, acute or chronic pelvic inflammatory disease)
-
Desire for future pregnancy
-
Significant systemic disease even if controlled
-
Pregnant or Positive pregnancy test
-
Hematocrit less than 25%
-
Extensive scarring along anterior lower abdominal wall (greater than 50% of area) or scar tissue or surgical clips in the direct path of the HIFU beam
-
MRI or MRI contrast agent contraindicated
-
Unable to quantify or measure fibroids on MR exam including nonenhancing fibroids
-
Fibroid or uterine calcifications
-
Dominant fibroid is pedunculated or greater than 5 cm submucosal
-
Communication barrier
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
| 2 | St. Luke's Episcopal Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Philips Healthcare
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Fennessy FM, Tempany CM, McDannold NJ, So MJ, Hesley G, Gostout B, Kim HS, Holland GA, Sarti DA, Hynynen K, Jolesz FA, Stewart EA. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. Radiology. 2007 Jun;243(3):885-93. Epub 2007 Apr 19.
- Flynn M, Jamison M, Datta S, Myers E. Health care resource use for uterine fibroid tumors in the United States. Am J Obstet Gynecol. 2006 Oct;195(4):955-64. Epub 2006 May 24.
- Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany C, Hynyen K, Mcdannold N, Inbar Y, Itzchak Y, Rabinovici J, Kim HS, Geschwind JF, Hesley G, Gostout B, Ehrenstein T, Hengst S, Sklair-Levy M, Shushan A, Jolesz F. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004 Dec;183(6):1713-9. Erratum in: AJR Am J Roentgenol. 2005 Jan;184(1):348. Hynnen, Kullvro [corrected to Hynyen, Kullervo]; Macdanold, Nathan [corrected to Mcdannold, Nathan]; Kim, Kevin [corrected to Kim, Hyun S]; Gostout, Brian [corrected to Gostout, Bobbie].
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Study Results
Participant Flow
| Recruitment Details | The first High Intensity Focused Ultrasound (HIFU) treatment was on February 8, 2009 and the last patient was treated on March 5, 2010. 2 study sites enrolled patients, 2 from St. Lukes in Houston, TX and 9 from National Institutes of Health in Bethesda, MD. |
|---|---|
| Pre-assignment Detail | Patients were screened prior to treatment and the primary exclusion criteria was either uterine size per gestational age or fibroid size. |
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Period Title: Overall Study | |
| STARTED | 11 |
| COMPLETED | 9 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Overall Participants | 11 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
11
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
46.7
(5.7)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
11
100%
|
| Male |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
11
100%
|
Outcome Measures
| Title | Treatment-related Adverse Events (AE) Per Subject Resulting From HIFU Treatment of the Uterine Fibroids |
|---|---|
| Description | The number of treatment-related Adverse Events (AE) reported during the study, divided by the total number of treated subjects. This corresponds to the mean number of treatment-related Adverse Events per subject. Relatedness of an AE to the treatment was judged case-by-case by the investigator. |
| Time Frame | end of follow-up (date of hysterectomy, at latest day 30 after treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety was assessed per protocol; all 11 participants were evaluated for adverse events after HIFU treatment. |
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Measure Participants | 11 |
| Mean (Full Range) [treatment-related AE/patient] |
1.3
(1.3)
|
| Title | HIFU Treatment Equals Location Per Hysterectomy |
|---|---|
| Description | Count the number of participants in which both of the following conditions are satisfied: the fibroid treated area as shown on MRI images during treatment is the same as displayed on fibroids from histology slices after hysterectomy, and no unintended lesions are visible in the uterus. |
| Time Frame | Day 0, Hysterectomy |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who underwent hysterectomy following MR-HIFU treatment were included in this endpoint measure. Patients who refused hysterectomy were not included. |
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Measure Participants | 9 |
| Number [participants] |
9
81.8%
|
| Title | Length of Time to Return to Normal Activities |
|---|---|
| Description | Length of time to return to normal activity measured in number of days from HIFU treatment. Assessed by patient interviews during follow-up. |
| Time Frame | end of follow-up (date of hysterectomy, at latest day 30 after treatment)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| per protocol |
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Measure Participants | 11 |
| Mean (Full Range) [days] |
1.4
|
| Title | Numerical Range Scale (NRS) of Pain Level |
|---|---|
| Description | Pain Scores obtained by patient self-assessment on a 0-10 scale, with 0 corresponding to no pain and 10 corresponding to maximum pain. |
| Time Frame | Treatment Day: Baseline, Recovery, Discharge; Follow-up: 24 hours, 48 hours, 72 hours, 1 week, 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects were included into analysis at a given time point if they had not received hysterectomy yet prior to that time point. Analysed subject numbers were: from baseline up to including 72 hours: 11 subjects (per protocol population); at 1 week: 6 subjects; at 2 weeks: 4 subjects; |
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Measure Participants | 11 |
| Treatment Day: Baseline |
1.3
(1.7)
|
| Treatment Day: Recovery |
2.6
|
| Treatment Day: Discharge |
1.4
|
| 24 hours after treatment |
2.4
|
| 48 hours after treatment |
1.5
|
| 72 hours after treatment |
1.3
|
| 1 week after treatment |
1.2
|
| 2 weeks after treatment |
1.5
|
| Title | Discomfort Level |
|---|---|
| Description | Patient's self-assessed discomfort level on a 4-point scale, with: 0 = no pain; 1 = mild; 2 = moderate; 3 = severe. |
| Time Frame | Treatment Day: Baseline, Recovery, Discharge; Follow-up: 24 hours, 48 hours, 72 hours, 1 week, 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects were included into analysis at a given time point if they had not received hysterectomy yet prior to that time point. Analysed subject numbers were: from baseline up to including 72 hours: 11 subjects (per protocol population); at 1 week: 6 subjects; at 2 weeks: 4 subjects; |
| Arm/Group Title | HIFU Treated |
|---|---|
| Arm/Group Description | Women indicated for total abdominal hysterectomy underwent a single Magnetic Resonance guided-High Intensity Focused Ultrasound (MR-HIFU) session for uterine fibroid ablation prior to surgery. Subjects were followed up until the date of hysterectomy, or for 30 days if hysterectomy was declined. |
| Measure Participants | 11 |
| Treatment Day: Baseline |
0.7
|
| Treatment Day: Recovery |
0.8
|
| Treatment Day: Discharge |
0.5
|
| 24 hours after treatment |
0.8
|
| 48 hours after treatment |
0.6
|
| 72 hours after treatment |
0.7
|
| 1 week after treatment |
0.3
|
| 2 weeks after treatment |
1.3
|
Adverse Events
| Time Frame | Feb 9, 2009 through March 9, 2010 | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events assessed by patient questionnaire. Only unexpected adverse events were reported in the "Other" Adverse Event Field. All adverse events were reported including those not related to treatment. | |
| Arm/Group Title | HIFU Treatment | |
| Arm/Group Description | ||
All Cause Mortality |
||
| HIFU Treatment | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| HIFU Treatment | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| HIFU Treatment | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/11 (54.5%) | |
| Gastrointestinal disorders | ||
| Rectal Bleeding | 1/11 (9.1%) | 1 |
| Diarrhea | 1/11 (9.1%) | 1 |
| Nausea | 1/11 (9.1%) | 1 |
| Constipation | 1/11 (9.1%) | 1 |
| General disorders | ||
| Pruritis | 1/11 (9.1%) | 1 |
| Fever | 1/11 (9.1%) | 1 |
| Cold | 1/11 (9.1%) | 1 |
| Injury, poisoning and procedural complications | ||
| Sharp burning pain at abdomen | 1/11 (9.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Neck Pain | 1/11 (9.1%) | 1 |
| Pain at Rib Cage or Chest Level | 2/11 (18.2%) | 4 |
| Right leg pain | 1/11 (9.1%) | 1 |
| Lower back pain | 1/11 (9.1%) | 1 |
| Shin discomfort | 1/11 (9.1%) | 1 |
| pain right buttock | 1/11 (9.1%) | 1 |
| Shoulder pain | 1/11 (9.1%) | 1 |
| Right foot swelling | 1/11 (9.1%) | 1 |
| Reproductive system and breast disorders | ||
| Fatigue | 1/11 (9.1%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Sarah Baxter |
|---|---|
| Organization | Philips Healthcare |
| Phone | 425-487-7665 |
| sarah.baxter@philips.com |
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