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

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ClinicalTrials.gov Identifier: NCT03020966
Recruitment Status : Recruiting
First Posted : January 13, 2017
Last Update Posted : October 24, 2018
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Tracking Information
First Submitted Date  ICMJE December 6, 2016
First Posted Date  ICMJE January 13, 2017
Last Update Posted Date October 24, 2018
Actual Study Start Date  ICMJE February 16, 2017
Estimated Primary Completion Date June 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
  • Pain with physical therapy on post-operative day 1 [ Time Frame: Post operative day 1 ]
    NRS questionnaire
  • Opioid Use [ Time Frame: Day of surgery to post-operative day 3 ]
    oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database
  • Opioid side effects [ Time Frame: Post-operative day 1 ]
    Opioid related symptom distress scale, ORSDS, composite score POD1
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
  • Postoperative pain after THR [ Time Frame: Post operative day 0 ]
    Questionnaire
  • Postoperative pain after THR [ Time Frame: Post operative day 1 ]
    Questionnaire
  • Postoperative pain after THR [ Time Frame: Postoperative day 2 ]
    Questionnaire
  • Postoperative pain after THR [ Time Frame: Postoperative day 3 ]
    Questionnaire
Change History Complete list of historical versions of study NCT03020966 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty
Official Title  ICMJE IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty: a Randomized, Blinded Trial
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pain, Postoperative
  • Opioid Use
Intervention  ICMJE
  • Drug: Acetaminophen
    Oral acetaminophen, intravenous placebo
  • Drug: Acetaminophen
    Intravenous acetaminophen, oral placebo
Study Arms  ICMJE
  • Experimental: Oral Tylenol
    Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo
    Intervention: Drug: Acetaminophen
  • Experimental: Intravenous Tylenol
    Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo
    Intervention: Drug: Acetaminophen
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2017)
154
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 16, 2019
Estimated Primary Completion Date June 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: George A Birch, BS 2127747377 birchg@hss.edu
Contact: Ahava Muskat, BS 2126061510 muskata@hss.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03020966
Other Study ID Numbers  ICMJE 2016-209
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospital for Special Surgery, New York
Study Sponsor  ICMJE Hospital for Special Surgery, New York
Collaborators  ICMJE Mallinckrodt
Investigators  ICMJE
Principal Investigator: Jacques Ya Deau, MD, PhD Hospital for Special Surgery, New York
PRS Account Hospital for Special Surgery, New York
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP