Clinical trial NCT02839876: Intravenous Versus Oral Acetaminophen in Primary Total Hip Arthroplasty
Official title: Comparison of Multimodal Analgesic Regimen With Intravenous Acetaminophen to Standard Oral Multimodal Therapy in Primary Total Hip Arthroplasty: A Randomized Controlled Double Blind Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis
Acetaminophen
Arthroplasty, Hip Replacement
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2016-07-21
Enrollment: 81
Sex: ALL
Minimum age (years): 56
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 24 Hour Opioid Consumption
timeFrame: 24 hours
Secondary outcomes:
measure: Opioid Consumption (Other)
timeFrame: 0-48 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (Preoperatively)
timeFrame: preoperatively
measure: Pain Scores, as Measured by the 11-point Numeric Rating Scale (NRS-11) (1 Hour After Arrival to PACU)
timeFrame: 1 hour after arrival to PACU
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (8 Hours)
timeFrame: 8 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (24 Hours)
timeFrame: 24 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (36 Hours)
timeFrame: 36 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (48 Hours)
timeFrame: 48 hours
measure: Subject Satisfaction at 24 Hours
timeFrame: 24 hours
measure: Subject Satisfaction at 48 Hours (48 Hours)
timeFrame: 48 hours
measure: Straight Leg Raise
timeFrame: Postoperative day 1
measure: Heel Slide Test
timeFrame: Postoperative day 1
measure: Number of Participants Able to Complete the Supine to Sit Test
timeFrame: Postoperative day 1
measure: Self-paced Walk Test
timeFrame: Postoperative day 1
measure: Number of Participants With Opioid-related Adverse Events
timeFrame: 0-72 hours
measure: Analgesic Consumption as Measured by Patient Diary
timeFrame: day 30
measure: Worst Pain (Day 30)
timeFrame: day 30
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (Preoperatively)
timeFrame: preoperatively
measure: Pain Scores, as Measured by the 11-point Numeric Rating Scale (NRS-11) (1 Hour After Arrival to PACU)
timeFrame: 1 hour after arrival to PACU
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (8 Hours)
timeFrame: 8 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (24 Hours)
timeFrame: 24 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (36 Hours)
timeFrame: 36 hours
measure: Subject Satisfaction at 48 Hours
timeFrame: 48 hours
measure: Pain Score, as Measured by the 11-point Numeric Rating Scale (NRS-11) (48 Hours)
timeFrame: 48 hours
Other outcomes:
measure: Hospital Length of Stay
timeFrame: 0-72 hours
measure: Overall Hospital Admission Costs
timeFrame: 0-72 hours
measure: Pharmacy-related Costs
timeFrame: 0-72 hours
measure: Costs Related to Opioid-related Adverse Events
timeFrame: 0-72 hours
measure: Cost Associated With Nursing Interventions and Drugs to Treat Opioid-related Adverse Events
timeFrame: 0-72 hours
Locations:
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
Study officials:
References: