Intravenous Versus Oral Acetaminophen in Primary Total Hip Arthroplasty

Phase 4

Completed

Conditions: Osteoarthritis
Acetaminophen
Arthroplasty, Hip Replacement

Interventions: Drug: Oral acetaminophen
Drug: Intravenous acetaminophen

Registration Number: NCT02839876

Lead Sponsor: Duke University

Brief Summary: The purpose of this study is to determine if intravenous acetaminophen is superior to oral acetaminophen when used as part of a multimodal pathway for primary total hip arthroplasty.

Detailed Description: This is a single center, prospective, randomized controlled study. 60 subjects will be recruited (see #6 Recruitment and Compensation below). On the day of surgery, subjects will be randomized to receive either the study intervention (intravenous acetaminophen and placebo tablets) or the control intervention (intravenous saline and active acetaminophen tablets). The Investigational Drug Service will prepare each intervention package, which will include one intravenous and one oral medication dose. Only one of these routes will be active (determined by randomization). Subjects will receive doses of both an intravenous and oral study drug every 6 hours in order to maintain blinding, and will receive a total of 4 doses of each (at 0, 6, 12 and 18 hours). The dose of acetaminophen in all cases will be 1000 mg. The volume of intravenous acetaminophen (and saline) will be 100 mL. The oral dose will consist of two (2) tablets of 500 mg each (or two matching placebo tablets).

All subjects will receive a standardized anesthetic regimen for total hip arthroplasty, as follows:

A) Preoperative phase

Subjects will receive the following preoperative multimodal drugs:

* Pregabalin 75 mg PO

* Celecoxib 200 mg PO

* The interventional drugs, both IV and PO . The time that these drugs are administered will be recorded as time zero. Patients will then receive a spinal anesthetic with 12.5 mg of isobaric bupivacaine. No peripheral nerve blocks will be performed.

B) Intraoperative phase All subjects will be receive propofol infusion beginning at 50 mg/kg/min and titrated to a Richmond Agitation-Sedation Scale score of -1 to -3 (drowsy to moderate sedation). Dexamethasone 10 mg IV and ketamine 0.25 mg/kg IV up to 40 mg total will be administered as part of the standard multimodal regimen. If required, subjects may receive fentanyl 25 mcg IV as needed to treat discomfort. No joint infiltration will be performed by the surgeon.

C) Postoperative phase In the Post-Anesthesia Care Unit (PACU), subjects will have an intravenous patient-controlled analgesia (IVPCA) device connected and loading doses of hydromorphone administered by the PACU nurse as necessary (0.2 mg q 8 min prn).

On the floor, subjects will receive:

* Pregabalin 75 mg PO BID until discharge

* Celecoxib 200 mg PO BID until discharge

* Dexamethasone 10 mg IV x 1 on postoperative day 1 (24 hours after the first dose)

* Intravenous patient-controlled analgesia (IVPCA) with hydromorphone (0.2 mg q 8 min).

The remaining 3 intervention packages (IV and PO) will be administered at 6, 12 and 18 hours following the first dose. At time point 24 hours (i.e. the fifth dose of acetaminophen), all subjects will begin to receive 975 mg of oral acetaminophen, continuing every six hours until discharge.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

Inclusion Criteria

Patients scheduled for elective, primary total hip replacement for osteoarthritis
American Society of Anesthesiologists (ASA) Physical Classification I-III
Weight 50 kg or greater
Body mass index 18-40 kg/m2

Exclusion Criteria

Inability to consent to study
Inability to speak English
Pregnancy
Weight <50 kg
Revision hip replacement or emergency surgery
Contraindications to spinal anesthesia: coagulopathy or bleeding diathesis, local infection, allergy to local anesthetics
Allergies/intolerances/contraindications to any of the multimodal agents: acetaminophen, pregabalin, celecoxib, ketamine, or dexamethasone
Chronic pain from a separate source other than operative hip
Daily opioid equivalent use of 30 mg of morphine or greater at time of consent
History of heart failure
History of drug or alcohol abuse
Rheumatoid arthritis
Uncontrolled anxiety, schizophrenia or other psychiatric disorder that, in the opinion of the investigator, may interfere with the study assessments
Chronic malnutrition, renal or liver impairment
Hypersensitivity to acetaminophen or any of its excipients

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral acetaminophen	Oral acetaminophen	Subjects receive 1000 mg acetaminophen PO immediately preoperatively, as well as at 6, 12, and 18 hours postoperatively. At the same time points, subjects will receive an intravenous placebo.
Intravenous acetaminophen	Intravenous acetaminophen	Subjects receive 1000 mg acetaminophen IV immediately preoperatively, as well as at 6, 12, and 18 hours postoperatively. At the same time points, subjects will receive an oral placebo.

Primary Outcome Measures

Name	Time	Method
24 Hour Opioid Consumption	24 hours	Cumulative dose of hydromorphone consumed in the first 24 hours postoperatively

Secondary Outcome Measures

Name	Time	Method
Opioid Consumption (Other)	0-48 hours	morphine equivalent units of intravenous and oral opioids
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (Preoperatively)	preoperatively	Pain scores (using NRS-11 scale) at rest. Participants rate their pain on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Pain Scores, as Measured by the 11-point Numeric Rating Scale (NRS-11) (1 Hour After Arrival to PACU)	1 hour after arrival to PACU	Pain scores (using NRS-11 scale) at with active range of motion of the hip. Participants rate their pain on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (8 Hours)	8 hours	Pain scores (using NRS-11 scale) with active range of motion of the hip. Participants rate their pain on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (36 Hours)	36 hours	Pain scores (using NRS-11 scale) with active range of motion of the hip. Participants rate their pain on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (24 Hours)	24 hours	Pain scores (using NRS-11 scale) with active range of motion of the hip. Participants rate their pain on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Self-paced Walk Test	Postoperative day 1	Time taken to walk down a hallway 20 m at a safe and quick pace, turn around and return to starting point.
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (48 Hours)	48 hours	Pain scores (using NRS-11 scale) with active range of motion of the hip. Participants rate their pain on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Subject Satisfaction at 24 Hours	24 hours	Overall subject satisfaction with hospital experience at the 24 hour time point using a simple 11-point Likert scale to quantify global satisfaction. 0=completely unsatisfied, 10=completely satisfied.
Subject Satisfaction at 48 Hours (48 Hours)	48 hours	Overall subject satisfaction with hospital experience at the 48 hour time point using a simple 11-point Likert scale to quantify global satisfaction. 0=completely unsatisfied, 10=completely satisfied.
Straight Leg Raise	Postoperative day 1	Number of participants who are able to complete the active straight leg test. The subject rests supine and is asked to lift his/her operative lower limb (with knee extended) until the ankle is 20 cm from level. If the subject can do this, the test is positive.
Heel Slide Test	Postoperative day 1	Number of participants who are able to complete the heel-slide test. The subject rests supine and is asked to place the heel of his/her operative side on the contralateral knee, then slide the heel down to the ankle and back in one continuous motion. If the subject can do this, the test is positive. If the subject cannot do this in one motion, or if pain or other factors prevent the test from being performed, the test is negative.
Number of Participants Able to Complete the Supine to Sit Test	Postoperative day 1	Number of participants able to go from supine to a sitting position independently.
Number of Participants With Opioid-related Adverse Events	0-72 hours	Incidence of respiratory desaturation events, nausea, vomiting, pruritis, ileus, and constipation
Analgesic Consumption as Measured by Patient Diary	day 30	morphine equivalent units of oral opioids and other non-opioids
Worst Pain (Day 30)	day 30	Participants are asked to rate their WORST pain on POSTOPERATIVE DAY 30 on an 11-point scale (0=no pain at all, 10=worst imaginable pain).
Subject Satisfaction at 48 Hours	48 hours	Overall subject satisfaction with hospital experience at the 48 hour time point using a simple 11-point Likert scale to quantify global satisfaction. 0=completely unsatisfied, 10=completely satisfied.