Intravenous Versus Oral Acetaminophen in Primary Total Hip Arthroplasty

Comparison of Multimodal Analgesic Regimen With Intravenous Acetaminophen to Standard Oral Multimodal Therapy in Primary Total Hip Arthroplasty: A Randomized Controlled Double Blind Trial

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis; Acetaminophen; Arthroplasty, Hip Replacement
• Intervention / Treatment: Drug: Intravenous acetaminophen; Drug: Oral acetaminophen

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Intravenous acetaminophen; Subject receives 1 g acetaminophen by the intravenous route every 6 hours for 4 doses beginning in the preoperative holding area.; Other Names: Ofirmev
Active Comparator: 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.	Drug: Oral acetaminophen; Subject receives 1 g acetaminophen by the oral route every 6 hours for 4 doses beginning in the preoperative holding area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 Hour Opioid Consumption	Cumulative dose of hydromorphone consumed in the first 24 hours postoperatively	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Consumption (Other)	morphine equivalent units of intravenous and oral opioids	0-48 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (Preoperatively)	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).	preoperatively
Pain Scores, as Measured by the 11-point Numeric Rating Scale (NRS-11) (1 Hour After Arrival to PACU)	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).	1 hour after arrival to PACU
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (8 Hours)	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).	8 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (24 Hours)	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).	24 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (36 Hours)	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).	36 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (48 Hours)	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).	48 hours
Subject Satisfaction at 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.	24 hours
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.	48 hours
Straight Leg Raise	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.	Postoperative day 1
Heel Slide Test	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.	Postoperative day 1
Number of Participants Able to Complete the Supine to Sit Test	Number of participants able to go from supine to a sitting position independently.	Postoperative day 1
Self-paced Walk Test	Time taken to walk down a hallway 20 m at a safe and quick pace, turn around and return to starting point.	Postoperative day 1
Number of Participants With Opioid-related Adverse Events	Incidence of respiratory desaturation events, nausea, vomiting, pruritis, ileus, and constipation	0-72 hours
Analgesic Consumption as Measured by Patient Diary	morphine equivalent units of oral opioids and other non-opioids	day 30
Worst Pain (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).	day 30
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (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).	preoperatively
Pain Scores, as Measured by the 11-point Numeric Rating Scale (NRS-11) (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).	1 hour after arrival to PACU
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (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).	8 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (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).	24 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (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).	36 hours
Subject Satisfaction at 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.	48 hours
Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (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).	48 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Length of Stay	Time to both discharge readiness and to actual discharge	0-72 hours
Overall Hospital Admission Costs	difference in total hospital admission cost between groups	0-72 hours
Pharmacy-related Costs	difference in pharmacy-related cost between groups	0-72 hours
Costs Related to Opioid-related Adverse Events	difference in cost related to treatment of opioid-related adverse events (nausea, vomiting, pruritis, constipation, respiratory depression, dizziness) between groups	0-72 hours
Cost Associated With Nursing Interventions and Drugs to Treat Opioid-related Adverse Events	mean cost (per patient) related to nursing care of opioid-related adverse events (nausea, vomiting, pruritis, constipation, respiratory depression, dizziness) in $USD	0-72 hours

Collaborators and Investigators

• Sponsor: Duke University

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2017
• Primary Completion (Actual): October 2, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (Estimate): July 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: Pro00072610

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No