IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty (IV Tylenol)
Primary Purpose
Pain, Postoperative, Opioid Use
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Acetaminophen
Acetaminophen
Sponsored by
About this trial
This is an interventional treatment trial for Pain, Postoperative
Eligibility Criteria
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
Sites / Locations
- Hospital for Special Surgery
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Oral Tylenol
Intravenous Tylenol
Arm Description
Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo
Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo
Outcomes
Primary Outcome Measures
Pain With Physical Therapy on Post-operative Day 1
Numerical rating scale of pain on a scale of 0-10, with 0 representing the minimum value of no pain and 10, representing the maximum, defined as being pain as bad as imaginable.
Opioid Use
Oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database.
Opioid Side Effects
The Opioid-Related Symptom Distress Scale (ORSDS) is a Likert scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. Frequency is rated on a 4-point scale (1= 'Rarely', 4= 'Almost constantly'). Severity is rated on a 4-point scale (1= 'Slightly', 4= 'Very'). Bothersomeness is rated on a 5-point scale (0.8= 'Not at all', 4.0= 'Very much'). The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS score is the average of 12 symptom-specific scores.
Secondary Outcome Measures
Full Information
NCT ID
NCT03020966
First Posted
December 6, 2016
Last Updated
August 9, 2021
Sponsor
Hospital for Special Surgery, New York
Collaborators
Mallinckrodt
1. Study Identification
Unique Protocol Identification Number
NCT03020966
Brief Title
IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty
Acronym
IV Tylenol
Official Title
IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty: a Randomized, Blinded Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
February 16, 2017 (Actual)
Primary Completion Date
June 16, 2019 (Actual)
Study Completion Date
June 16, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital for Special Surgery, New York
Collaborators
Mallinckrodt
4. Oversight
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
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Opioid Use
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
154 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral Tylenol
Arm Type
Experimental
Arm Description
Patient group receiving 1000mg of oral acetaminophen and an intravenous placebo
Arm Title
Intravenous Tylenol
Arm Type
Experimental
Arm Description
Patient group receiving 1000mg of intravenous acetaminophen and an oral placebo
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Description
Oral acetaminophen, intravenous placebo
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Description
Intravenous acetaminophen, oral placebo
Primary Outcome Measure Information:
Title
Pain With Physical Therapy on Post-operative Day 1
Description
Numerical rating scale of pain on a scale of 0-10, with 0 representing the minimum value of no pain and 10, representing the maximum, defined as being pain as bad as imaginable.
Time Frame
24 hours after the operation (post-operative day 1)
Title
Opioid Use
Description
Oral morphine equivalents, cumulative, POD 0-3. Recorded in Medication Usage Database.
Time Frame
Day of surgery to post-operative day 3
Title
Opioid Side Effects
Description
The Opioid-Related Symptom Distress Scale (ORSDS) is a Likert scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. Frequency is rated on a 4-point scale (1= 'Rarely', 4= 'Almost constantly'). Severity is rated on a 4-point scale (1= 'Slightly', 4= 'Very'). Bothersomeness is rated on a 5-point scale (0.8= 'Not at all', 4.0= 'Very much'). The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS score is the average of 12 symptom-specific scores.
Time Frame
24 hours after surgery (Post-operative day 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques Ya Deau, MD, PhD
Organizational Affiliation
Hospital for Special Surgery, New York
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Citations:
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25995489
Citation
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Results Reference
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Results Reference
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IV vs. Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty
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