Leiomyoma, Uterine Fibroids
Conditions
Brief summary
PLUM evaluates the drug letrozole as a treatment for uterine fibroids. This study is a randomized, blinded, placebo-controlled trial of oral letrozole among premenopausal women with symptomatic uterine fibroids. Participants will be randomly assigned in a 1:1 ratio to either oral letrozole 2.5mg/day for 6 months (Group A) or intermittent dosing with letrozole 2.5mg/day and an identical placebo capsule (Group B).
Interventions
DRUGLetrozole
OTHERPlacebo
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥21 years old 2. Premenopausal (at least one menses in last 3 months) 3. Symptomatic fibroids (fibroids visualized on ultrasound or MRI and heavy uterine bleeding, pelvic pressure or discomfort, urinary or bowel abnormalities, dyspareunia) 4. Fibroids that are ≤4 in total number or Fibroids that are ≤7 in total number if all fibroids are less than 4cm (40 mm) each 5. Fibroids that are ≤7cm in maximum diameter, on screening imaging, if ≤4 fibroids in total number(fibroid is defined as any mass with radiographic characteristics of fibroid \>2cm) 6. Up to date in Pap smear screening and surveillance 7. Endometrial biopsy (required if age\>45 years with irregular bleeding) does not indicate premalignant or malignant cells 8. Agree to use non-hormonal barrier method of contraception during study period if at risk for pregnancy 9. Has primary care provider or gynecologist 10. Agrees not to start new medications/treatments for fibroids during the study 11. Able to give informed consent
Exclusion criteria
1. Fibroids treated by surgery, radiologic procedure, or GnRH agonist or antagonist in the last 3 months 2. Any submucosal fibroid ≥2cm that is \>50% in uterine cavity (FIGO Type 0 or Type 1 fibroids) amenable to hysteroscopic resection 3. Use of exogenous estrogen and/or progestin in the last month. (for 3 month long-acting depoprovera injection, no use in last 3 months) 4. Pregnant, lactating, or planning to become pregnant in the next 6 months 5. Hematocrit \<27% or visit to emergency room or hospitalization for fibroid symptoms in the last 3 months (cannot be safely randomized to a placebo) 6. History of osteopenia or osteoporosis 7. History of hyperlipidemia 8. Current liver or kidney disease 9. Unable or unwilling to attend 4 study visits 10. Pelvic imaging concerning for gynecologic cancer or cancer of the genitourinary or gastrointestinal system 11. Does not have primary care provider or gynecologist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Fibroid-related Symptoms After Treatment With Letrozole | Baseline to 2 Months | The Uterine Fibroid Sympton and Quality of Life (UFS-QoL) Symptom Severity score measures self-reported severity of fibroid-related symptoms. Symptoms include: fatigue, sleep, self-image, mood disturbances/psychologic distress, fear of embarrassment, interference with daily activities, relationships with family and friends, and sexual functioning. Scores range from 0 to 100; higher scores indicate greater symptom severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Letrozole Oral letrozole 2.5mg/day | 6 |
| Placebo and Letrozole Intermittent oral letrozole 2.5mg/day for 2 months and an identical placebo capsule for 4 months | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Letrozole | Placebo and Letrozole | Total |
|---|---|---|---|
| Age, Continuous | 46.33 years STANDARD_DEVIATION 4.2 | 39.50 years STANDARD_DEVIATION 7.4 | 42.92 years STANDARD_DEVIATION 6.8 |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latina | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race reported | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White or Caucasian | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| UFS-QOL Symptom Severity Score | 53.65 units on a scale STANDARD_DEVIATION 25 | 42.71 units on a scale STANDARD_DEVIATION 9 | 48.18 units on a scale STANDARD_DEVIATION 18.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Changes in Fibroid-related Symptoms After Treatment With Letrozole
The Uterine Fibroid Sympton and Quality of Life (UFS-QoL) Symptom Severity score measures self-reported severity of fibroid-related symptoms. Symptoms include: fatigue, sleep, self-image, mood disturbances/psychologic distress, fear of embarrassment, interference with daily activities, relationships with family and friends, and sexual functioning. Scores range from 0 to 100; higher scores indicate greater symptom severity.
Time frame: Baseline to 2 Months
Population: The final analysis excludes one participant in the placebo/letrozole group who dropped out of the study after baseline but prior to starting study medication and the Month 2 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Letrozole | Changes in Fibroid-related Symptoms After Treatment With Letrozole | -10.42 units on a scale |
| Placebo and Letrozole | Changes in Fibroid-related Symptoms After Treatment With Letrozole | 1.43 units on a scale |
Comparison: Null hypotheses: Letrozole is not associated with an improvement in the UFSQOL Overall Score.p-value: 0.2495% CI: [-32.92, 9.23]Mixed Models Analysis