Symptomatic Uterine Fibroids and Adenomyosis Clinical Trial
Official title:
A Prospective, Double Blind, Randomized, Placebo Controlled Study to Compare the Effectiveness of Intravenous Acetaminophen and Intravenous Ibuprofen in Reducing Post Procedural Pain in the Uterine Fibroid Embolization Procedure
The uterine fibroid embolization (UFE) procedure is a treatment option for abnormal heavy
menstrual bleeding and/or bulk symptoms associated with uterine fibroids and adenomyosis.
Post UFE procedural pain and nausea are expected events. These symptoms are treated with
current standard of care medications, including opiates.
Intra procedure pain medications include midazolam, fentanyl and hydromorphone. Some centers
include nonsteroidal anti-inflammatory medications (NSAIDS), including oral ibuprofen and IV
ketorolac. Post procedural pain control is centered on a hydromorphone patient-controlled
analgesia (PCA) infusion pump, as well as a NSAID regimen. Intra procedure and post procedure
nausea control medications include a transcutaneous scopolamine patch and IV anti-nausea
medications such as ondansetron and prochlorperazine.
This study is being conducted to compare two new medications for pain, IV ibuprofen and IV
acetaminophen, administered for 24 hours following UFE. The primary safety objective of
non-inferiority will be met and the primary efficacy objective of superiority, decreased pain
and nausea, will be accessed when compared to current standard of care regimens.
This is a 4 arm, double blind, randomized, controlled study. All patients will receive
standard of care baseline pain medications, including IV midazolam, fentanyl and
hydromorphone intra procedure, followed by a hydromorphone PCA infusion pump post procedure.
The 4 arms will include: [ Arm 1] IV ibuprofen/IV placebo, [Arm 2] IV acetaminophen/IV
placebo, [Arm 3] IV ibuprofen/IV acetaminophen, and [arm 4] IV placebo/IV placebo. These
medications will be given during the procedure and extended over a 24 hour stay.
Arm 4 (IV placebo/IV placebo) would replicate current standard of care, and therefore will
include IV push (IVP) ketorolac, which would be given at the end of the procedure and be
continued every 6 hours for the 24 hour stay. An IVP of saline will be given as a control
every 6 hours for the 24 hour stay to arms 1, 2 and 3. Pain and nausea will be measured at
intervals prior to the procedure, throughout the stay and at 2 weeks post procedure.
A prospective, double blind, randomized controlled trial evaluating the effects of two new IV
medications, IV ibuprofen and IV acetaminophen, on standard of care pain and anti-emetic
management in Uterine Fibroid Embolization patients.
1. Four arm, double blind, randomized controlled study: all patients will receive standard
of care baseline pain medications, including IV midazolam, fentanyl and hydromorphone
during the procedure, followed by a hydromorphone PCA infusion pump during their
recovery. The four arms will include an IV ibuprofen/IV placebo, an IV acetaminophen/IV
placebo, an IV ibuprofen/IV acetaminophen, and a control arm (IV placebo/IV placebo).
The same amount of normal saline will be substituted for the experimental treatments if
the patient receives the placebo. These medications will be given during the procedure
and extended over a 24 hour recovery period. The medications given will be blinded to
the patient, the administrator, and the surveyor.
2. The placebo/placebo arm would replicate current standard of care, and therefore include
IV push (IVP) ketorolac, which would be given at the end of the procedure and be
continued for 24 hours at q6hour dosing. An IVP of saline would be given as a control
for 24 hours at q6hour dosing to the other three arms.
3. Dosage of medications will be standardized based on formulary indications: IV Ketorolac
30 mg/dose IVP, acetaminophen 1 gram/dose IV piggy back over 15 minutes every 6 hours,
ibuprofen 800 mg/dose IV piggy back over 30 minutes every 6 hours.
4. Variables measured: mean and maximum pain (VAS score at 0 hours, 6 hours, discharge and
2 weeks post procedure), opioid requirements, mean and maximum nausea (VAS score at 0
hours, 6 hours, discharge and 2 weeks post procedure), anti-emetic medication
requirements.
Weighted sum of pain intensity differences, with pain intensity measured on VAS over 24
hours (SPID24) will be used as a primary outcome. Satisfaction scores will be measured
at 24 hours using the validated APS-POQ-R questionnaire (6).
5. Other variables recorded: Age, height, weight, history of postoperative nausea and
vomiting or motion sickness, diagnosis, uterine volume, dominant fibroid size, arteries
embolized, presence of prominent ovarian arteries, volume of particle used, fluoroscopy
time for the procedure.
6. Technical parameters, which would remain constant, include: pre procedure and 6 month
follow up MRI contrast with gadolinium which is standard of care, embolization using
500-700 micron Embospheres (with limited use of 700-900 micron Embospheres), IV
hydration with 0.9% normal saline, antibiotics (IV ciprofloxacin 400 mg every 12 hours,
IV metronidazole 500 mg every six hours), urinary catheter placement, lower extremity
compression devices, and early ambulation.
7. In the interim analysis, the investigators will have 40 subjects in total with unequal
randomization ratio of 1:1:4:4. Additional subjects will be enrolled for a total of 35
subjects per arm for the final analysis (sum total N=140)
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