IV vs Oral Acetaminophen in Spine Fusion Perioperative Care

Single-Center, Randomized Controlled Trial of Intravenous v Oral Acetaminophen Administration in Perioperative Care of 1 and 2 Level XLIFs Supplemented With Bilateral Pedicle Screw Stabilization: a Comparative Effectiveness Study

The United States is currently experiencing an explosive opioid epidemic. In 2014 alone, 28,647 Americans died from an opioid associated overdose; the annual death toll has increased by over 300% since 2000. The epidemic poses a complex scenario for physicians administering treatment for postoperative pain, as opioids are key analgesic agents in treating moderate to severe pain. In order to reduce the patients risk for long term opioid use and the associated side effects, physicians have begun shifting to multimodal analgesic approaches to treat postoperative pain. These approaches have been found to be similarly efficacious, while also reducing opioid usage and associated side effects, such as: nausea, vomiting, and ileus.

This study proposes a multimodal analgesic approach, which the investigators believe will reduce short and long term opioid usage, the associated side effects, and the financial burden. Intravenous acetaminophen is an effective medication for both primary and adjunctive pain management, however its use is limited by a high cost to perceived benefit ratio. Oral acetaminophen is a relatively inexpensive option, although perhaps less effective than the IV option, and also often not feasible to utilize in the immediate post-operative period when patients are unable to safely swallow pills. The hypothesis of this investigation is to understand if adding intravenous acetaminophen to the perioperative care regimen after lumbar spinal surgery will result in improved pain management in the perioperative period while decreasing opioid usage and related complications.

Study Overview

• Status: Enrolling by invitation
• Conditions: Multimodal Analgesic Approach
• Intervention / Treatment: Drug: Per Os Acetaminophen; Drug: Ofirmev

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosis of spinal stenosis of the lumbar spine with degenerative spondylolisthesis
• Skeletally mature adults between the ages of 18-85 years at the time of surgery
• The greater of the patients right and left VAS leg pain, or back pain, score is > 40 mm on a 100 mm scale
• Has attempted conservative therapy
• Psychosocially, mentally, and physically able to fully comply with this protocol, including adhering to scheduled visits, treatment plan, completing forms, and other study procedures
• Personally signed and dated informed consent document prior to any study-related procedures indicating that the patient has been informed of all pertinent aspects of the study

Exclusion Criteria:

• Any evidence of a prior/current fracture, compromised vertebra, current or past trauma, or tumor at affected level or the spinous processes at the adjacent levels
• Revision of prior fusion attempt at the level being operated on
• Cauda Equina Syndrome defined as neural compression causing neurogenic bowel (rectal incontinence) or bladder dysfunction (bladder retention or incontinence)
• Significant peripheral neuropathy or acute denervation secondary to radiculopathy, caused by conditions other than spinal stenosis
• Significant peripheral vascular disease (diminished dornails pedis or tibial pulses)
• Morbid obesity, defined as BMI > 40 kg/m2; or underweight, defined as BMI < 18.5 kg/m2
• Active systematic or local infection
• Active Viral Hepatitis (receiving medical treatment within 1 year); or any other acute hepatitis within the past 6 months
• Immunocompromised such as but not limited to Acquired Immunodeficiency Syndrome (AIDS), HIV infection, Severe Combined Immunodeficiency Syndrome, Thymic Hypoplasia
• Insulin dependent diabetes mellitus or any other medical conditions that would represent a significant increase in surgical risk or interfere with normal healing
• Immunologically suppressed, or has received systemic steroids, excluding nasal steroids, at any dose for >1 month within last 12 months
• History of Paget's disease, osteomalacia, or osteoporosis with a DEXA t-score less than or equal to -2.5
• Active malignancy. A patient with a history of any invasive malignancy (except non-melanoma skin cancer), unless treated with curative intent and there has been no clinical signs or symptoms of the malignancy >5 years
• Any current history of substance abuse (e.g., recreational drugs, narcotics, or alcohol)
• History of psychosocial disorders that could prevent accurate completion of self-reporting assessment scales
• Previous known allergy to acetaminophen
• Women who are pregnant or lactating
• Patients involved in active litigation relating to his/her spinal condition
• Patients taking >30mg/day of oral morphine sulfate, or the equivalent of this daily for more than 3 months
• Patient is unable to ingest orally administered medication
• Patient receiving autologous Iliac Crest bone graft (ICBG)
• Known intolerance of or true allergy to hydromorphone or oxycodone.
• History of moderate to severe Cirrhosis, defined as Child Pugh score of class B, C, or D
• History of Hemochromatosis or Porphyria
• Patient taking Isoniazid or barbiturates

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PO Acetaminophen; Preop: Eligible patients will receive oral acetaminophen within 3 hours of OR start time. Postop: Eligible patients will be administered oral acetaminophen following 1 and 2 level LLIFs supplemented with instrumented posterior fusion to evaluate pain management outcomes. Dosing for the group will be the following: • Oral Acetaminophen 1,000 mg every 6 hours for 48 hours postoperative. Medication will be given at least 6 hours following initial preoperative dose of oral acetaminophen. Postop supplemental pain medications: All patients will receive a standardized hydromorphone IV-PCA order set for 24 hours postoperatively. The use of tramadol and tapentadol will specifically be discouraged due to challenges in determining morphine-equivalent dosing with these specific agents. Similarly, acetaminophen containing combination products (e.g. oxycodone/acetaminophen or hydrocodone/acetaminophen) will not be allowed due to overlap with the primary study medications.	Drug: Per Os Acetaminophen; Orally administered acetaminophen.
Active Comparator: Intravenous Acetaminophen; Preop: Eligible patients will receive IV acetaminophen within 3 hours of OR start time. Postop: Eligible patients will be administered IV acetaminophen following 1 and 2 level LLIFs supplemented with instrumented posterior fusion to evaluate pain management outcomes. Dosing for the group will be the following: • IV Acetaminophen 1,000 mg [100 ml] every 6 hours for 48 hours postoperative. Medication will be given at least 6 hours following initial preoperative dose of IV acetaminophen. Postop supplemental pain medications: All patients will receive a standardized hydromorphone IV-PCA order set for 24 hours postoperatively. The use of tramadol and tapentadol will specifically be discouraged due to challenges in determining morphine-equivalent dosing with these specific agents. Similarly, acetaminophen containing combination products (e.g. oxycodone/acetaminophen or hydrocodone/acetaminophen) will not be allowed due to overlap with the primary study medications.	Drug: Ofirmev; Intravenously administered acetaminophen.; Other Names: Intravenous Acetaminophen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS) for back and legs	Self reported pain frequency and intensity at 24 hour postoperative intervals until patient is discharged, at 6 week and 6 month follow-up. The scale is scored on a 100 mm line, with 0 being no pain and 100 being worst pain imaginable.	Change from baseline VAS at 6 months postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay (LOS)	Measured in total hours until discharge from hospital	Immediate postoperative
Opioid Equivalent Dosing during Hospital Stay	Measured every 24 hours postoperative until discharge from hospital	Postoperative
Time to Ambulation	Measured in total hours postoperative until patient is ambulatory	Immediate postoperative
Oswestry Disability Index Version 2.1 (ODI)		Preoperative, 6 weeks and 6 months postoperative
Long Term Opioid Usage		6 months Postoperative

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Chad Craig, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: July 5, 2016
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimated): January 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pain management; Acetaminophen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 2015-516

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED