Intravenous Versus Oral Acetaminophen in Primary Total Hip Arthroplasty

NCT ID: NCT02839876

Last Updated: 2021-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-14
• Study Completion Date: 2018-10-31

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.

Conditions

Osteoarthritis; Acetaminophen; Arthroplasty, Hip Replacement

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Intravenous acetaminophen

Intervention Type: DRUG

Subject receives 1 g acetaminophen by the intravenous route every 6 hours for 4 doses beginning in the preoperative holding area.

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.

Group Type: ACTIVE_COMPARATOR

Oral acetaminophen

Intervention Type: DRUG

Subject receives 1 g acetaminophen by the oral route every 6 hours for 4 doses beginning in the preoperative holding area.

Interventions

Intravenous acetaminophen

Subject receives 1 g acetaminophen by the intravenous route every 6 hours for 4 doses beginning in the preoperative holding area.

Intervention Type: DRUG

Oral acetaminophen

Subject receives 1 g acetaminophen by the oral route every 6 hours for 4 doses beginning in the preoperative holding area.

Intervention Type: DRUG

Other Intervention Names

Ofirmev

Eligibility Criteria

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

• Minimum Eligible Age: 56 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Duke University Hospital

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00072610

Identifier Type: -

Identifier Source: org_study_id