MODIV-APAP: Modified Pre-operative Oral Doses Acetaminophen Versus Intravenous Acetaminophen

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT02994940
• Collaborator: (none)
• Enrollment: 74
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.1
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

Acetaminophen is frequently used as an adjunct for pain management in pediatric surgical patients. The drug is available in an over the counter, inexpensive oral form as well as a considerably more expensive intravenous form. This study will compare opioid requirements and acetaminophen plasma levels post operatively for two dosing regimens to compare oral versus intravenous routes given pre operatively.

Condition or Disease	Intervention/Treatment	Phase
Tonsillectomy; Adenoidectomy	Drug: Acetaminophen	Phase 4

Detailed Description

The primary purpose of this study is to compare opioid utilization in post-operative patients undergoing tonsillectomy and adenoidectomy, between IV and PO acetaminophen. Secondarily, it will provide information regarding possible cost savings, pharmacokinetics and safety between these two regimens.

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Modified Pre-operative Oral Doses Acetaminophen Versus Intravenous Acetaminophen
• Actual Study Start Date: Aug 28, 2017
• Actual Primary Completion Date: Jul 3, 2019
• Actual Study Completion Date: Jul 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Acetaminophen Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.	Drug: Acetaminophen; already included in arm/group descriptions; Other Names: OFIRMEV
Experimental: Intravenous Acetaminophen Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.	Drug: Acetaminophen; already included in arm/group descriptions; Other Names: OFIRMEV

Outcome Measures

Primary Outcome Measures

1. Total Dose of Opioid [Within 24hrs]

   Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.

Secondary Outcome Measures

1. Proportion of Patients With Severe Pain Score of 7 or Higher [24 hrs period following surgery]

   A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.

2. Plasma Acetaminophen Level 1 - End of Surgery [at the end of surgery, about 1 hour after IV Dose]

   mg/L acetaminophen in the plasma at the end of surgery

3. Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration [Outcome will be measured 3hrs post first IV Dose]

   mg/L acetaminophen in the plasma 3 hours after IV study drug administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients ages 3 years to 17 years scheduled for tonsillectomy and adenoidectomy for obstructive sleep apnea with or without additional minor procedures such as sleep endoscopy, unilateral or bilateral myringotomy, insertion of tympanostomy tubes and/or ear exam. ( Minor additional procedures that are frequently combined with tonsillectomy and adenoidectomy but are not commonly considered to have pain that is significantly greater than the tonsillectomy and adenoidectomy).

Exclusion Criteria:

• Patients who meet University of California Davis Children's Hospital (UCDCH) criteria for Pediatric Intensive Care Unit (PICU) admission: on home oxygen pre-operatively, exhibit airway obstruction when awake (stertor above larynx, stridor at larynx), sleep study with apnea hypoxia index greater than 25 or sleep oxygen saturation nadir <80%, cardiac disease, difficult intubation.

• Patients with a known allergy to acetaminophen

• Patients with known hepatic insufficiency or severe hepatic disease

• Patients with known Glucose-6-phosphate dehydrogenase (G6PD) deficiency

• Patients who are malnourished (ie lower levels of glutathione)

• Patients with severe renal impairment as defined by calculated creatinine clearance <20 ml/min (per modified Schwarz equation)

• Patients who are pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Children's Hospital	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis

Investigators

• Principal Investigator: Cathy Lammers, MD, UC Davis Children's Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 18, 2016
• Informed Consent Form - Aug 2, 2017

More Information

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT02994940
• Other Study ID Numbers: 948256
• First Posted: Dec 16, 2016
• Last Update Posted: Feb 18, 2021
• Last Verified: Jan 1, 2021

• 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
• Additional relevant MeSH terms: Acetaminophen

Study Results

Participant Flow

Arm/Group Title	Oral Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen	Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen
Period Title: Overall Study
STARTED	37	37
COMPLETED	30	36
NOT COMPLETED	7	1

Baseline Characteristics

Arm/Group Title	Oral Acetaminophen	Intravenous Acetaminophen	Total
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen	Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen	Total of all reporting groups
Overall Participants	30	36	66
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	4	6	5
Sex: Female, Male (Count of Participants)
Female	15 50%	14 38.9%	29 43.9%
Male	15 50%	22 61.1%	37 56.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Weight (kg) (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	19.3	20.6	20.2
Percentile weight for age (percentile) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [percentile]	55.0	45.0	49.5

Outcome Measures

1. Primary Outcome

Title	Total Dose of Opioid
Description	Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.
Time Frame	Within 24hrs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen	Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen
Measure Participants	30	36
Median (Inter-Quartile Range) [mcg/kg]	147.6	125.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.127
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Hodges Lehman estimator
	Estimated Value	21.3
	Confidence Interval	(2-Sided) 95%; -2.5 to 44.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Patients With Severe Pain Score of 7 or Higher
Description	A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.
Time Frame	24 hrs period following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen	Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen
Measure Participants	30	36
Count of Participants [Participants]	15 50%	17 47.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.851
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Plasma Acetaminophen Level 1 - End of Surgery
Description	mg/L acetaminophen in the plasma at the end of surgery
Time Frame	at the end of surgery, about 1 hour after IV Dose

Outcome Measure Data

Analysis Population Description

2 patients in Oral did not have sample obtained for level; 1 patient in IV had value below 10 mg/L limit of quantification

Arm/Group Title	Oral Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen	Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen
Measure Participants	28	35
Median (Inter-Quartile Range) [mg/L]	22	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Hodges Lehman estimator
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -1.0 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration
Description	mg/L acetaminophen in the plasma 3 hours after IV study drug administration
Time Frame	Outcome will be measured 3hrs post first IV Dose

Outcome Measure Data

Analysis Population Description

Acetaminophen plasma levels obtained 3 hours after start of the IV study drug in patients with samples obtained; these were not available for 8 Oral and 9 IV subjects.

Arm/Group Title	Oral Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen	Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen
Measure Participants	21	16
Median (Inter-Quartile Range) [mg/L]	18	11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Hodges Lehman estimator
	Estimated Value	7.0
	Confidence Interval	(2-Sided) 95%; 4.0 to 8.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	24 hours
Arm/Group Title	Oral Acetaminophen		Intravenous Acetaminophen
Arm/Group Description	Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision. Acetaminophen		Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision. Acetaminophen
All Cause Mortality
	Oral Acetaminophen		Intravenous Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/36 (0%)
Serious Adverse Events
	Oral Acetaminophen		Intravenous Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Oral Acetaminophen		Intravenous Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.