Comparing Pain Improvement for Intravenous Versus Oral Acetaminophen in Acute Pelvic Pain: A Randomized, Double-Blind, Double-Dummy Controlled Trial (PIVOTAL Trial)
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- Montefiore Medical Center
- Enrollment
- 140
- Locations
- 1
- Primary Endpoint
- Mean Change in Numeric Rating Scale (NRS) score
Study Overview
Brief Summary
The investigator team proposes a randomized, double-blind, double-dummy comparative effectiveness trial conducted in two urban emergency departments (EDs) in the Bronx, New York. This study is designed to determine the relative efficacy of IV acetaminophen compared to PO acetaminophen in treating pelvic pain. This design focuses on the early onset of action and short-term efficacy, which may better capture potential differences between IV and PO acetaminophen in the acute ED setting.
Detailed Description
An estimated 70% of Emergency Department (ED) visits involve pain as a complaint. Although ED practice has shifted away from routine opioid prescribing, uncertainty remains regarding optimal selection among commonly used non-opioid analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Medication selection varies by pain etiology, and among patients presenting with musculoskeletal pain, opioids (40.7%), acetaminophen (37.8%), and NSAIDs (22.6%) remain the most frequently administered medications in the ED.
Pain in women has been comparatively understudied. Pelvic pain is common among women of childbearing age, and chronic pelvic pain affects up to 24% of women overall. In nonpregnant women, NSAIDs are widely considered first-line therapy for both acute and chronic pelvic pain. In pregnant women and in those attempting to conceive, NSAIDs are typically avoided. Observational studies have associated NSAID use around the time of conception or prior to 20 weeks' gestation with an increased risk of miscarriage, while acetaminophen has not shown a similar association. NSAID exposure in early pregnancy has also been linked to congenital anomalies.
Guidelines recommend limiting opioid use during pregnancy and in women of childbearing age. Opioid exposure has been associated with congenital anomalies and with poorer maternal and neonatal outcomes. As a result, opioids are generally avoided as first-line therapy for pelvic pain in patients who are pregnant or may be pregnant.
Therefore, it is routine to ascertain pregnancy status prior to administering NSAIDs or opioids to women of childbearing age for an informed decision making discussion. Acetaminophen, in contrast, is generally considered safe in pregnancy and can be administered without delay while awaiting pregnancy testing. Acetaminophen is associated with relatively mild side effects, which may vary by route of administration.
Pharmacokinetic studies demonstrate that intravenous acetaminophen achieves higher peak plasma concentrations and faster central nervous system penetration than oral administration. Outside the ED, IV acetaminophen has been associated with faster onset of meaningful pain relief and reduced opioid use in some surgical populations. Whether these pharmacologic advantages translate into clinically meaningful improvements in acute pelvic pain management in the Emergency Department for patients of childbearing potential with pelvic pain is unclear.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Allocation concealment will be maintained using sequentially numbered medication kits prepared by the research pharmacy. Participants, treating clinicians, research staff, outcome assessors, and investigators will remain blinded to treatment allocation.
Eligibility Criteria
- Ages
- 16 Years to 50 Years (Child, Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Female sex at birth
- •Presentation to the Emergency Department (ED) with pelvic pain
- •Baseline numeric pain score (NRS) ≥4
- •Ability to provide informed consent in English or Spanish
Exclusion Criteria
- •Receipt of any analgesic medication within 2 hours or acetaminophen within 6 hours
- •Known allergy or intolerance to acetaminophen
Arms & Interventions
Intravenous Drug + Oral Placebo
Intravenous Acetaminophen + PO placebo
IV Acetaminophen 1000mg
No additional analgesics will be administered prior to two hours unless clinically indicated. Rescue analgesia may be administered at any time at the discretion of the treating clinician.
Intervention: IV Acetaminophen 1000mg (Drug)
Intravenous Drug + Oral Placebo
Intravenous Acetaminophen + PO placebo
IV Acetaminophen 1000mg
No additional analgesics will be administered prior to two hours unless clinically indicated. Rescue analgesia may be administered at any time at the discretion of the treating clinician.
Intervention: PO Placebo (Other)
Oral Drug + IV Placebo
Oral Acetaminophen 1000mg + IV placebo
Oral Acetaminophen 1000mg
No additional analgesics will be administered prior to two hours unless clinically indicated. Rescue analgesia may be administered at any time at the discretion of the treating clinician.
Intervention: Acetaminophen 1000mg PO (Drug)
Oral Drug + IV Placebo
Oral Acetaminophen 1000mg + IV placebo
Oral Acetaminophen 1000mg
No additional analgesics will be administered prior to two hours unless clinically indicated. Rescue analgesia may be administered at any time at the discretion of the treating clinician.
Intervention: IV Placebo (Other)
Outcomes
Primary Outcomes
Mean Change in Numeric Rating Scale (NRS) score
Time Frame: From baseline to 30 minutes following medication administration
Mean Change in NRS score will be assessed at 30 minutes post-treatment. The NRS is a patient self-assessment pain scale that instructs patients to use a facial grimace scale ranging from 0-10 rating to express pain intensity, wherein 0 is "No pain" and 10 is "Worst pain possible," such that higher scores are indicative of greater pain intensity. For purposes of the primary outcome change in NRS score from baseline will be assessed. Results will be summarized by study arm using descriptive statistics.
Secondary Outcomes
- Pain Intensity(0-, 5-, 10-, 15-, 30-, 45-, 60- and 120-minutes following medication administration)
- Time to Clinically Meaningful Reduction in Pain(Within 2 hours after medication administration)
- Use of Rescue Medications(Within 2 hours following medication administration)
- Patient Global Impression of Change (PGI-C) Score(30- and 120-minutes following medication administration)
- Treatment-Related Adverse Events (TRAEs)(Within 2 hours following medication administration)
- Emergency Department (ED) Disposition(At 2 hours following medication administration)
- Length of Stay (LOS)(Less than 24 hours following medication administration)
- Patient Satisfaction(At 2 hours following medication administration)