Effectiveness of IV Acetaminophen and IV Ibuprofen in Reducing Post Procedural Pain in the UFE Procedure
Condition: Symptomatic Uterine Fibroids and Adenomyosis
MeSH terms: Leiomyoma; Myofibroma; Adenomyosis; Pain, Procedural
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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)
    

Intervention name(s): IV Ibuprofen; IV Acetaminophen; Intravenous placebo/Intravenous placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Uterine fibroid embolization; Uterine fibroid embolization; Uterine fibroid embolization
Other intervention name(s): Uterine artery embolization; Uterine artery embolization; Uterine artery embolization
Intervention MeSH terms: Acetaminophen; Ibuprofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: Uterine Fibroid Embolization; Pain; UFE; Fibroids; Adenomyosis; Bleeding; IV Acetaminophen; IV Ibuprofen; Menorrhagia; Leiomyoma; Patient Satisfaction