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IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty (IV Tylenol)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03020966
Recruitment Status : Recruiting
First Posted : January 13, 2017
Last Update Posted : October 24, 2018
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Brief Summary:
The purpose of this study is to determine how well two different methods of administrating Tylenol reduce pain and improve patient satisfaction after total hip replacement (THR) surgery. The methods of administration are orally, via a pill that is to be swallowed, and intravenously. Our aim is to determine whether oral or intravenous administration of Tylenol will reduce opioid consumption and opioid-related side effects after THR.

Condition or disease Intervention/treatment Phase
Pain, Postoperative Opioid Use Drug: Acetaminophen Phase 4

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Detailed Description:

A) Opioid use after THA. Opioid use after THA can be 90 mg (+/-79) in morphine equivalents when using epidural bupivacaine / hydromorphone and multimodal analgesia. Less than 1/3 of this was via the epidural (26/90 mg). Patients reported ORSDS composite scores of 0.58

B) IV vs oral acetaminophen. The therapeutic blood concentration of acetaminophen for pain relief is 10 mcg/ml.

After an oral, single dose: In 24 fasting adult subjects, the maximal blood concentration (Cmax) of 7.7 to 17.6 mcg/mL occurred within 1 hour following a single 1000-mg dose of oral acetaminophen (liquid or caplet). Acetaminophen crosses the blood-brain barrier. Central diffusion to the brain and spinal fluid occurs within 15 to 45 minutes with maximum cerebrospinal fluid concentrations occurring at 2 to 4 hours. [Product Information: TYLENOL(R) oral, acetaminophen oral. McNeil Consumer Healthcare, Skillman, NJ, 2010].

In a randomized, double-blind, placebo-controlled, single-dose study, acetaminophen 1,000 mg provided significantly greater efficacy in treating postsurgical dental pain compared with acetaminophen 650 mg and placebo.

Oral, multiple-dose, immediate-release, elderly patients: In 12 very elderly patients (mean age, 89 years), the Cmax was 23.9 mcg/mL following the administration of acetaminophen 1000 mg orally 3 times daily for 5 days.

In adult subjects, the mean Cmax was 28 +/- 21 mcg/mL at the end of a 15-minute IV infusion of acetaminophen 1000 mg. [Product Information: OFIRMEV(TM) intravenous infusion, acetaminophen intravenous infusion. Cadence Pharmaceuticals Inc., San Diego, CA, 2010].

The oral medication has an excellent absorption and at least 85% bioavailability, but peak concentration occurs later than the IV, and the therapeutic blood concentration for pain relief (10mcg/ml) may not be achieved after one oral dose (7-17mcg/ml).A full stomach delays the absorption. With multiple doses, in elderly patients, or with renal/ liver failure, the blood concentration is higher.

Epidural bupivacaine / clonidine (Liu). Pain scores (NRS) after THA with activity on POD1 can be 3.4 mean (2.6 SD) when using epidural bupivacaine / clonidine and multimodal analgesia.

Low-opioid protocol (oxycodone may be too strong for some; cannot use Vicodin due to acetaminophen) Choice of instruments (CAM, ORSDS, Pain OUT). The ORSDS is a 4-point scale that evaluates 12 symptoms (nausea, vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness or difficulty staying awake, feeling lightheaded or dizzy, feeling confused, feelings of general fatigue or weakness, itchiness, dry mouth and headache) via 3 symptom distress dimensions (frequency, severity, bothersomeness). It is validated for use after orthopaedic surgery, specifically including TKA patients receiving epidural analgesia and femoral nerve blockade.

Patients can meet criteria for delirium by CAM by having acute onset of inattention as well as either disorganized thinking or altered level of consciousness.Patients without acute onset can also meet criteria for delirium if inattention, disorganized thinking and altered level of consciousness are all present, with at least one factor judged to be fluctuating. CAM has been widely applied and has been specifically used to evaluate elderly TKA patients receiving epidural analgesia and femoral nerve blockade.

The Patient Outcome Questionnaire by the American Pain society is used for quality improvement, and measures 6 aspects of quality, including (1) pain severity and relief; (2) impact of pain on activity, sleep, and negative emotions; (3) side effects of treatment; (4) helpfulness of information about pain treatment; (5) ability to participate in pain treatment decisions; and (6) use of nonpharmacological strategies.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty: a Randomized, Blinded Trial
Actual Study Start Date : February 16, 2017
Estimated Primary Completion Date : June 16, 2019
Estimated Study Completion Date : June 16, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Oral Tylenol
Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo
Drug: Acetaminophen
Oral acetaminophen, intravenous placebo

Experimental: Intravenous Tylenol
Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo
Drug: Acetaminophen
Intravenous acetaminophen, oral placebo

Primary Outcome Measures :
  1. Pain with physical therapy on post-operative day 1 [ Time Frame: Post operative day 1 ]
    NRS questionnaire

  2. Opioid Use [ Time Frame: Day of surgery to post-operative day 3 ]
    oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database

  3. Opioid side effects [ Time Frame: Post-operative day 1 ]
    Opioid related symptom distress scale, ORSDS, composite score POD1

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Adult
  • Scheduled for an elective primary THA with a participating surgeon,
  • Planned for Combined Spinal Epidural anesthesia (CSE) and Patient Controlled Epidural Analgesia (PCEA)
  • English-speaking
  • Patients that did not receive pre-operative opioids

Exclusion criteria:

  • Hepatic or renal insufficiency, as defined by abnormal readings on liver and kidney functioning tests.
  • Hypersensitivity or contraindication to protocol medication
  • Contraindication for CSE and PCEA
  • Incapable to provide consent/answer questions in English
  • Revision or urgent surgery
  • Receiving Periarticular Injections
  • History of opioid use
  • Patients on disability or worker's compensation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03020966

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Contact: George A Birch, BS 2127747377
Contact: Ahava Muskat, BS 2126061510

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United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: George A Birch, BS    212-774-7377   
Contact: Ahava Muskat, BS    2126061510   
Principal Investigator: Jacques YaDeau, MD, PhD         
Principal Investigator: Geoffrey H Westrich, MD         
Sponsors and Collaborators
Hospital for Special Surgery, New York
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Principal Investigator: Jacques Ya Deau, MD, PhD Hospital for Special Surgery, New York


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Responsible Party: Hospital for Special Surgery, New York Identifier: NCT03020966     History of Changes
Other Study ID Numbers: 2016-209
First Posted: January 13, 2017    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018

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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
Additional relevant MeSH terms:
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Pain, Postoperative
Postoperative Complications
Pathologic Processes
Neurologic Manifestations
Signs and Symptoms
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs