The Effectiveness of IV/PO Acetaminophen in the Perioperative Period in Reducing Opiate Use After Lumbar Spine Fusion

• Sponsor: University of Southern California (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03104816
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 3
• Duration (Months): 14
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

Simple explanation and rationale:

Recovery after spine surgery is usually accompanied by severe pain which has traditionally been managed with opioids. It is common practice to supplement opioid treatment with different classes of analgesics which work through alternative pain pathways and receptors in order to achieve an additive or synergistic effect while reducing the amount of opioids necessary for pain control.

Acetaminophen can be a beneficial supplemental analgesic to opioids for postoperative pain relief.

Intervention:

Patients will be randomized to either the treatment with IV acetaminophen (A), PO acetaminophen (B), or hydromorphone control group (C).

Objective/Purpose:

Primary objective is to determine the impact of administering a supplemental non-opioid analgesic drug such as IV or PO acetaminophen on total opioid dose administered over the postoperative period.

Secondary objectives include investigating the impact of IV/PO acetaminophen on the level of postoperative pain, patient satisfaction, and side effects secondary to opioids such as nausea, vomiting, pruritus, sedation, respiratory depression, ileus, and urinary retention, and PACU (postoperative care unit) discharge time.

Study population:

126 patients will be enrolled in the study (42 for group A, 42 for group B, and 42 for control group C).

Follow-up and Endpoints / Outcomes:

Postoperative assessments will be done at 0, 30, and 60 minutes, 6 hours, 12 hours and 24 hours after surgery. Patients will be evaluated for pain (using a numeric rating scale), total opioid consumption, and for opioid side effects including drowsiness (using the Ramsey sedation scale and the Aldrete score at the time of arrival to and discharge from recovery room), respiratory depression, nausea, vomiting, and pruritus. Patient satisfaction will also be assessed using a numeric rating scale.

Condition or Disease	Intervention/Treatment	Phase
Fusion of Spine, Lumbar Region	Drug: Acetaminophen IV Soln 10 MG/ML; Drug: Acetaminophen; Drug: Hydromorphone	Phase 4

Detailed Description

Simple explanation and rationale:

Recovery after spine surgery, especially spinal fusion surgery, is usually accompanied by severe pain which has traditionally been managed with opioids. While opioids have been proven effective, they are associated with undesirable side effects including nausea, vomiting, pruritus, sedation, respiratory depression, ileus, and urinary retention leading to increased time required in recovery and a decrease in patient satisfaction. For this reason, it is common practice to supplement opioid treatment with different classes of analgesics which work through alternative pain pathways and receptors in order to achieve an additive or synergistic effect while reducing the amount of opioids necessary for pain control.

Acetaminophen is a centrally-acting cyclooxygenase inhibitor nonsteroidal anti-inflammatory medication that has minimal, if any, gastrointestinal and platelet-inhibiting side effects, and is better tolerated by patients than other cyclooxygenase inhibitors. This medication can be a beneficial supplemental analgesic to opioids for postoperative pain relief. Previously conducted studies demonstrate a rationale for the use of intravenous/PO acetaminophen in a multimodal analgesic regimen to reduce postoperative analgesia.

Intervention:

Patients will be randomized to either the treatment with IV acetaminophen (A), PO acetaminophen (B), or hydromorphone control group (C). Patients who are randomized to group A will receive 1 g of IV acetaminophen during the wound closure and every 4 to 6 hours postoperatively for a total of 4 g in 24 hours. Patients who are randomized to group B will receive 1 g of PO acetaminophen before surgery and every 4 to 6 hours postoperatively for a total of 4 g in 24 hours. Patients who are randomized to control group C will not receive acetaminophen. Post-operatively, patients in both groups will also receive IV hydromorphone PCA (patient-controlled analgesia) only for 24 hours for pain.

Objective/Purpose:

Primary objective is to determine the impact of administering a supplemental non-opioid analgesic drug such as IV or PO acetaminophen on total opioid dose administered over the postoperative period.

Secondary objectives include investigating the impact of IV/PO acetaminophen on the level of postoperative pain, patient satisfaction, and side effects secondary to opioids such as nausea, vomiting, pruritus, sedation, respiratory depression, ileus, and urinary retention, and PACU discharge time.

Study population:

126 patients will be enrolled in the study (42 for group A, 42 for group B, and 42 for control group C).

Follow-up and Endpoints / Outcomes:

Postoperative assessments will be done at 0, 30, and 60 minutes, 6 hours, 12 hours and 24 hours after surgery. Patients will be evaluated for pain (using a numeric rating scale), total opioid consumption, and for opioid side effects including drowsiness (using the Ramsey sedation scale and the Aldrete score at the time of arrival to and discharge from recovery room), respiratory depression, nausea, vomiting, and pruritus. Patient satisfaction will also be assessed using a numeric rating scale.

Statistics:

All sample size calculations with reference to:

• Specific Aim 1 reduction of opioid intake by at least 25% between the Control (Group C) and Intervention Groups A and B, and

• Specific Aim 2 improvement of Pain Score by at least 25% between the Control (Group C) and the Intervention Groups A and B,

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effectiveness of IV/PO Acetaminophen in the Perioperative Period in Reducing Opiate Use After Lumbar Spine Fusion: a Prospective, Randomized Controlled Trial
• Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acetaminophen IV Soln 10 MG/ML (A) Patients in group A will receive 1 g of IV acetaminophen 15 minutes prior to wound incision, and every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours.	Drug: Acetaminophen IV Soln 10 MG/ML; Other Names: Ofirmev ; Drug: Hydromorphone; Other Names: Dilaudid
Experimental: PO acetaminophen (B) Patients in group B will receive 1 g of PO acetaminophen prior to surgery, and 1 g of oral acetaminophen every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours.	Drug: Acetaminophen; Other Names: Tylenol ; Drug: Hydromorphone; Other Names: Dilaudid
Active Comparator: Hydromorphone (control arm) (C) Patients in the control arm (Group C) will not receive acetaminophen for 24 hours.	Drug: Hydromorphone; Other Names: Dilaudid

Outcome Measures

Primary Outcome Measures

1. Postoperative Opioid Use [Within 24 hours after surgery]

   Determine the impact of administering a supplemental non-opioid analgesic drug such as IV/oral acetaminophen on total opioid dose administered over the perioperative period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• ASA (American Society of Anesthesiologists) I-III patients scheduled for elective one or two level minimally invasive lumbar fusions

Exclusion Criteria:

• Patients requiring surgery for neoplastic processes

• Allergy to acetaminophen

• Liver dysfunction and elevated Liver Function Tests (LFTs)

• Alcohol or drug dependency

• Mental retardation

• Less than 50 kg of weight

• regnant women

• Patients requiring long-acting opioid pain management (including fentanyl patch, oxycontin, etc) for over 3 weeks immediately prior to surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keck Hospital of USC	Los Angeles	California	United States	90033

Sponsors and Collaborators

• University of Southern California

Investigators

• Principal Investigator: Eugenia Ayrian, University of Southern California

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 28, 2016

More Information

Publications

• Cakan T, Inan N, Culhaoglu S, Bakkal K, Başar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. J Neurosurg Anesthesiol. 2008 Jul;20(3):169-73. doi: 10.1097/ANA.0b013e3181705cfb.
• Devin CJ, McGirt MJ. Best evidence in multimodal pain management in spine surgery and means of assessing postoperative pain and functional outcomes. J Clin Neurosci. 2015 Jun;22(6):930-8. doi: 10.1016/j.jocn.2015.01.003. Epub 2015 Mar 9. Review.
• Garcia RM, Cassinelli EH, Messerschmitt PJ, Furey CG, Bohlman HH. A multimodal approach for postoperative pain management after lumbar decompression surgery: a prospective, randomized study. J Spinal Disord Tech. 2013 Aug;26(6):291-7. doi: 10.1097/BSD.0b013e318246b0a6.
• Korkmaz Dilmen O, Tunali Y, Cakmakkaya OS, Yentur E, Tutuncu AC, Tureci E, Bahar M. Efficacy of intravenous paracetamol, metamizol and lornoxicam on postoperative pain and morphine consumption after lumbar disc surgery. Eur J Anaesthesiol. 2010 May;27(5):428-32. doi: 10.1097/EJA.0b013e32833731a4.

• Responsible Party: Eugenia Ayrian, Associate Professor of Clinical Anesthesiology;Chief of Neuro Anesthesiology, University of Southern California
• ClinicalTrials.gov Identifier: NCT03104816
• Other Study ID Numbers: HS-15-00615
• First Posted: Apr 7, 2017
• Last Update Posted: Oct 8, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Eugenia Ayrian, Associate Professor of Clinical Anesthesiology;Chief of Neuro Anesthesiology, University of Southern California: Acetaminophen po; Acetaminophen IV; Pain management; minimally invasive lumbar fusions; Ofirmev; Analgesics; Opioid; Pain; Postoperative; Spinal
• Additional relevant MeSH terms: Acetaminophen; Hydromorphone

Study Results

Participant Flow

Recruitment Details	28 patients were involved in study. 22 patients completed the study. Patients were recruited in the surgical clinic, preoperative clinic, preoperative surgical area.
Pre-assignment Detail	Patients were included in the study according to their inclusion and exclusion criteria. There were no patients were excluded from study in the period after signing the consent to assignment to groups.

Arm/Group Title	Acetaminophen IV Soln 10 Milligram/Milliliter (MG/ML) (A)	PO Acetaminophen (B)	Hydromorphone (Control Arm) (C)
Arm/Group Description	Patients in group A will receive 1 g of IV acetaminophen 15 minutes prior to wound incision, and every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours. Acetaminophen IV Soln MG/ML Hydromorphone	Patients in group B will receive 1 g of PO acetaminophen prior to surgery, and 1 g of oral acetaminophen every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours. Acetaminophen Hydromorphone	Patients in the control arm (Group C) will not receive acetaminophen for 24 hours. Hydromorphone
Period Title: Overall Study
STARTED	11	11	6
COMPLETED	9	9	4
NOT COMPLETED	2	2	2

Baseline Characteristics

Arm/Group Title	Acetaminophen IV Soln 10 MG/ML (A)	PO Acetaminophen (B)	Hydromorphone (Control Arm) (C)	Total
Arm/Group Description	Patients in group A will receive 1 g of IV acetaminophen 15 minutes prior to wound incision, and every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours. Acetaminophen IV Soln 10 MG/ML Hydromorphone	Patients in group B will receive 1 g of PO acetaminophen prior to surgery, and 1 g of oral acetaminophen every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours. Acetaminophen Hydromorphone	Patients in the control arm (Group C) will not receive acetaminophen for 24 hours. Hydromorphone	Total of all reporting groups
Overall Participants	9	9	4	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 33.3%	5 55.6%	3 75%	11 50%
>=65 years	6 66.7%	4 44.4%	1 25%	11 50%
Sex: Female, Male (Count of Participants)
Female	5 55.6%	9 100%	1 25%	15 68.2%
Male	4 44.4%	0 0%	3 75%	7 31.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 11.1%	2 22.2%	0 0%	3 13.6%
Not Hispanic or Latino	8 88.9%	7 77.8%	4 100%	19 86.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%	9 100%	4 100%	22 100%
Number of analyzed participants in each group (Count of Participants)
Count of Participants [Participants]	9 100%	9 100%	4 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Postoperative Opioid Use
Description	Determine the impact of administering a supplemental non-opioid analgesic drug such as IV/oral acetaminophen on total opioid dose administered over the perioperative period.
Time Frame	Within 24 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acetaminophen IV Soln 10 MG/ML (A)	PO Acetaminophen (B)	Hydromorphone (Control Arm) (C)
Arm/Group Description	Hydromorphone and IV Acetaminophen are given to this group	Hydromorphone and PO acetaminophen are given to this group	Hydromorphone only is given to the patients in this group
Measure Participants	9	9	4
PACU dose	1.2 (0.4)	1.3 (0.3)	1.7 (0.5)
Ward dose	9.8 (2.9)	10.4 (3.1)	13 (5.5)

Adverse Events

Time Frame	Adverse events were collected within 24 hours.
Arm/Group Title	Acetaminophen IV Soln 10 MG/ML (A)		PO Acetaminophen (B)		Hydromorphone (Control Arm) (C)
Arm/Group Description	Patients in group A will receive 1 g of IV acetaminophen 15 minutes prior to wound incision, and every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours. Acetaminophen IV Soln 10 MG/ML Hydromorphone No adverse events.		Patients in group B will receive 1 g of PO acetaminophen prior to surgery, and 1 g of oral acetaminophen every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours. Acetaminophen Hydromorphone No adverse events.		Patients in the control arm (Group C) will not receive acetaminophen for 24 hours. Hydromorphone No adverse events.
All Cause Mortality
	Acetaminophen IV Soln 10 MG/ML (A)		PO Acetaminophen (B)		Hydromorphone (Control Arm) (C)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/4 (0%)
Serious Adverse Events
	Acetaminophen IV Soln 10 MG/ML (A)		PO Acetaminophen (B)		Hydromorphone (Control Arm) (C)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Acetaminophen IV Soln 10 MG/ML (A)		PO Acetaminophen (B)		Hydromorphone (Control Arm) (C)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/4 (0%)

Limitations/Caveats

The trial was not completed and had very small amount of participants.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.