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Equality Study of Ofirmev vs Oral Acetaminophen

Primary Purpose

Pain, Postoperative

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
IV acetaminophen
oral acetaminophen
Sponsored by
Babiash, Kimberly H., M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring oral acetaminophen, IV acetaminophen, Ofirmev, equianalgesic, arthroscopic rotator cuff repair

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Age โ‰ฅ18
  • Weight 75kg -120 kg
  • Undergoing arthroscopic rotator cuff repair by same surgeon at Surgicare of Wichita
  • Patients who sign informed consent
  • Patients who do not meet any of the exclusion criteria

Exclusion Criteria:

  • Age < 18 yrs (will reduce risk of overdosing oral acetaminophen)
  • History of opioid abuse or chronic opioid use greater than 3 months (may skew data with regards to pain control due to the concept of tolerance)
  • Acetaminophen allergy (avoids risk of allergic reaction)
  • Liver disease as determined by anesthesiologist by history (acetaminophen involves the liver for metabolism, therefore, if the liver is not functioning appropriately, doses could accumulate and cause damage.)
  • Daily alcohol consumption (same explanation as for liver disease)
  • Renal failure (patient on dialysis or health history indicates renal dysfunction) (acetaminophen has some renal excretion)
  • Asthma (recent concerns for acetaminophen leading to asthma exacerbations)
  • Any other contraindication to taking acetaminophen
  • Surgeon requested pre-operative Interscalene block (this will cause the patient to cease having pain, therefore the effects of acetaminophen reducing pain scores will not be able to be evaluated)
  • Current warfarin, carbamazepine, or phenytoin use (these medications can accumulate in the presence of excessive acetaminophen use or may harm the liver and affect acetaminophen use or may harm the liver and affect acetaminophen concentrations).
  • Weight greater than 120 kg (1.5 gram doses of acetaminophen may be too low to appropriately evaluate the effects in this patient population)
  • Patients scheduled for "possible rotator cuff repair" (including these patients in our studies could skew enrollment numbers should a rotator cuff repair not be done, so these patients will be screened and excluded prior to enrollments)
  • Any consumption of acetaminophen containing products in the 24 hour period prior to surgery (excluded because acetaminophen can induce its own metabolism, therefore reducing serum concentrations)
  • Any significant medical disease(s), laboratory abnormalities or condition(s) that in the Investigator's judgment could compromise the subject's welfare, ability to communicate with the study staff, complete study activities, or would otherwise contraindicate study participation.
  • Non-English speaking patients
  • Patients who are not able to consent for themselves.
  • pregnant patients (All female patients of childbearing potential are given a pregnancy test prior to any elective surgery at Surgicare. Though acetaminophen is NOT harmful to these patients, they will be excluded given the fact that elective surgery in itself is contraindicated in pregnancy)

Sites / Locations

  • Surgicare of Wichita

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Group I: IV acetaminophen

group 2

Arm Description

Group I will receive 1 gram IV acetaminophen 15 minutes prior to going to the operating room for arthroscopic rotator cuff repair

Group 2 will receive 1.5grams of oral acetaminophen immediately prior to proceeding to the operation groom for arthroscopic rotator cuff surgery

Outcomes

Primary Outcome Measures

Primary outcome will measure total opioid consumption while the patient is in the PACU
opioid consumption will be evaluated by the postoperative nurses who are blinded to the study groups

Secondary Outcome Measures

time from PACU admission to request for first opioid dose
post operative nurses will record time to request for first opioid

Full Information

First Posted
October 17, 2012
Last Updated
January 27, 2015
Sponsor
Babiash, Kimberly H., M.D.
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1. Study Identification

Unique Protocol Identification Number
NCT01711229
Brief Title
Equality Study of Ofirmev vs Oral Acetaminophen
Official Title
Prospective Randomized Equivalence Trial Comparing the Analgesic Efficacy of Ofirmevยฎ Compared to a 1.5 Gram Dose of Oral Acetaminophen for Arthroscopic Rotator Cuff Repair
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Unknown status
Study Start Date
December 2015 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Babiash, Kimberly H., M.D.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Acetaminophen (Tylenol) is a drug that is used commonly for relief of mild to moderate pain. It is found in many pain medicines that people take after having surgery. Narcotics are other drugs also used for pain (examples of narcotics are morphine and related pain medications). Medical science knows for a fact that acetaminophen works well when taken with narcotics for moderate to severe pain. Recently, acetaminophen has become available in an intravenous (IV) form called Ofirmevยฎ. The IV form means that acetaminophen can be given into a vein. The benefits of getting medicine from an IV include: making the medicine work quickly less medicine having to pass through the liver to be changed into a form that your body can process The investigators know that acetaminophen is helpful for pain relief at the time of surgery and after surgery. Acetaminophen is a very popular drug in outpatient surgery for pain control when patients go home. The patient's surgeon uses it to control pain after surgery at home in the form of Lortab or Percocet (Lortab and Percocet also have a narcotic medicine that mixes with acetaminophen). Also, currently at Surgicare, some anesthesiologists give intravenous acetaminophen while the patient is waiting to go to surgery. The investigators currently do not give any patient acetaminophen by mouth BEFORE surgery. However, since the addition of the IV form to the drug market, there has been interest to see if the oral form is just as good or better in reducing pain after surgery. This is why we are asking patients to join our study. The goal of this study is to find out if the oral form (by mouth) or the IV form (given into a vein) of acetaminophen controls pain after surgery better.
Detailed Description
The American Society of Anesthesiologists recommends acetaminophen, NSAIDS, or COX-2 inhibitors as part of a multimodal pain management strategy to limit opioid usage (1). As the surgical patient population becomes more complex with comorbidities ranging from obesity, obstructive sleep apnea , and asthma becoming more common, the medical community continues to search for efficacious analgesics with a high safety profile. While non-steroidal anti-inflammatory drugs play an important role in multi-modal analgesia, their use is limited based on concerns for platelet inhibition, asthma exacerbation, and renal artery perfusion in patients of advanced age or reduced creatinine clearance. Acetaminophen has proven to be an important analgesic in the perioperative setting. It is frequently combined with opiates to allow for synergism, or it can be used as a sole analgesic to provide up to 4 hours of relief for moderate pain. While acetaminophen's main role as a multimodal analgesic regimen has been in tablet form as an opioid/acetaminophen combination in the post- anesthesia care unit (PACU), acetaminophen has emerged as an important perioperative analgesic due to FDA approval of an intravenous (IV) formulation (Ofirmevยฎ) in the United States in 2010. While the new intravenous formulation was approved based upon its postoperative effectiveness and safety, there is also an interest in its preoperative use. [12, 13] The benefit IV acetaminophen claims over the oral modality is a 70% higher blood concentration than a single similar dose (1 gram) of oral acetaminophen and a rapid onset with peak blood concentration within 15 minutes of infusion while similar oral doses may take 90 minutes to reach peak plasma concentrations. Many studies have compared the IV formulation of acetaminophen (Ofirmevยฎ) with the oral formulation at the same dose of 1 gram. However, this does not take into account the difference in pharmacokinetics of oral and intravenous formulations. A 15-minute constant infusion of 1 gram acetaminophen resulted in an average plasma concentration of 25.02 ฮผg/ml at the end of the infusion with subsequent decline to approximately 11 ฮผg/ml at 1 hour and 7 ฮผg/ml at 3 hour after the start of infusion. Pain scores were lowest at one hour but remained significantly low for at least three hours. [FDA med review] Moreover, the pharmacokinetics of the immediate release oral formulation of acetaminophen are well-known. The absorption half life for acetaminophen in healthy subjects ranges from 0.06-0.7 hours (8). The relative bioavailability ranges from 85% to 98%. Moreover, it has a low first pass metabolism with a hepatic extraction ratio of 0.11 to 0.37 (9). After oral administration of 1 gram acetaminophen in the immediate release formulation (IR), peak concentrations of acetaminophen in adults ranged from 7.7 to 17.6 ฮผg/mL within 1 hour. Although the therapeutic range for acetaminophen is not well established, plasma concentrations of 10-20 mcg/ml are associated with antipyretic activity, and previous work has assumed that antipyretic and analgesic doses will be similar. (3-4). However, another study developed two compartmental pharmacokinetic/pharmacodynamic models to relate plasma concentration to pain score relationship in children who received oral acetaminophen 30 minutes before outpatient tonsillectomy. The model demonstrated only a one point decrease in pain score when the concentration increased from 10 ฮผg/mL to 20 ฮผg/mL and a steep loss of pain protection when the concentration fell below 6 - 7 ฮผg/mL. Therefore, this study indicates a saturation of the analgesic effect of acetaminophen at a threshold plasma concentration of as low as 7 ฮผg/mL. The basis for our proposal stems from a recent study by J Van Der Westhuizen, et al. They set out to determine if the traditional one gram unit dose reached adequate serum concentrations of greater than 10 mcg/ml. They compared 1 gram each of intravenous (IV) and oral acetaminophen to see if one or both achieved therapeutic plasma concentrations peri-operatively and for how long. This study questioned the use of oral acetaminophen at 1 gram because if it was not achieving therapeutic concentrations, the patients were not getting optimal care (5). From this study, they were able to extrapolate oral doses of 20 mg/kg that would achieve a maximum concentration of 19 mcg/ml (which is the median maximum concentration achieved by IV acetaminophen). The study concluded that for subjects over 75 kg, an effective IV equivalent oral acetaminophen dose would be 1.5 grams or even 2 grams if the subject exceeded 100 kg (5). This study further recommended a follow up study to evaluate these higher doses of oral acetaminophen as it relates to pain scores and rescue medications postoperatively compared to the IV dose of 1 gram. The current unit dose of oral acetaminophen is 1 gram every 6 hours. However, many studies have evaluated the effects of higher doses of oral acetaminophen as well (10, 11). One study supported the use of 5-6 grams of acetaminophen in a 24- hour period in order to reduce requirements for postoperative morphine. requirements (6). Another study measured serum and CSF concentrations one hour after administration of 500 mg, 1 gm, 1.5 gm, or 2 gm of oral acetaminophen (7). In summary, the investigator's hypothesis is that while a similar dose is less effective, a 1.5 gram dose of oral acetaminophen (as determined by the extrapolation of maximum serum concentrations from the Van Der Westhuizen, et al. study (5)) may be as effective as 1.0 gram of IV acetaminophen in reducing postoperative pain scores and total opioid consumption, thus resulting in lower cost to the patient and provider. II. Specific Aims: The investigator's aim is to compare the effects of a 1.5 gram oral acetaminophen to 1 gram IV acetaminophen when given preoperatively to patients undergoing arthroscopic rotator cuff repair by a single surgeon at a single facility. The primary outcomes will evaluate total opioid consumption in the post anesthesia care unit PACU and nominal pain scores. The investigators theorize that 1.5 grams of oral acetaminophen will be as efficacious as 1 gram IV acetaminophen resulting in lower costs to the patient and provider.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative
Keywords
oral acetaminophen, IV acetaminophen, Ofirmev, equianalgesic, arthroscopic rotator cuff repair

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group I: IV acetaminophen
Arm Type
Active Comparator
Arm Description
Group I will receive 1 gram IV acetaminophen 15 minutes prior to going to the operating room for arthroscopic rotator cuff repair
Arm Title
group 2
Arm Type
Active Comparator
Arm Description
Group 2 will receive 1.5grams of oral acetaminophen immediately prior to proceeding to the operation groom for arthroscopic rotator cuff surgery
Intervention Type
Drug
Intervention Name(s)
IV acetaminophen
Other Intervention Name(s)
Ofirmev
Intervention Description
Ofirmev will be given 15 minutes prior to going to the OR
Intervention Type
Drug
Intervention Name(s)
oral acetaminophen
Other Intervention Name(s)
tylenol
Intervention Description
oral acetaminophen will be given preoperatively
Primary Outcome Measure Information:
Title
Primary outcome will measure total opioid consumption while the patient is in the PACU
Description
opioid consumption will be evaluated by the postoperative nurses who are blinded to the study groups
Time Frame
From arrival in the recovery room until discharged from the recovery to home, which is an estimated time period of 2 hours
Secondary Outcome Measure Information:
Title
time from PACU admission to request for first opioid dose
Description
post operative nurses will record time to request for first opioid
Time Frame
from admission into the recovery room until the patient is discharged to home which is an estimated average of 2 hours
Other Pre-specified Outcome Measures:
Title
Nominal pain scores
Description
post operative nurses will assess pain scores from 1-10 in 5 minute intervals and follow a pain intervention protocol
Time Frame
from admission into the recovery room until discharged to home which is an estimated average of 2 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age โ‰ฅ18 Weight 75kg -120 kg Undergoing arthroscopic rotator cuff repair by same surgeon at Surgicare of Wichita Patients who sign informed consent Patients who do not meet any of the exclusion criteria Exclusion Criteria: Age < 18 yrs (will reduce risk of overdosing oral acetaminophen) History of opioid abuse or chronic opioid use greater than 3 months (may skew data with regards to pain control due to the concept of tolerance) Acetaminophen allergy (avoids risk of allergic reaction) Liver disease as determined by anesthesiologist by history (acetaminophen involves the liver for metabolism, therefore, if the liver is not functioning appropriately, doses could accumulate and cause damage.) Daily alcohol consumption (same explanation as for liver disease) Renal failure (patient on dialysis or health history indicates renal dysfunction) (acetaminophen has some renal excretion) Asthma (recent concerns for acetaminophen leading to asthma exacerbations) Any other contraindication to taking acetaminophen Surgeon requested pre-operative Interscalene block (this will cause the patient to cease having pain, therefore the effects of acetaminophen reducing pain scores will not be able to be evaluated) Current warfarin, carbamazepine, or phenytoin use (these medications can accumulate in the presence of excessive acetaminophen use or may harm the liver and affect acetaminophen use or may harm the liver and affect acetaminophen concentrations). Weight greater than 120 kg (1.5 gram doses of acetaminophen may be too low to appropriately evaluate the effects in this patient population) Patients scheduled for "possible rotator cuff repair" (including these patients in our studies could skew enrollment numbers should a rotator cuff repair not be done, so these patients will be screened and excluded prior to enrollments) Any consumption of acetaminophen containing products in the 24 hour period prior to surgery (excluded because acetaminophen can induce its own metabolism, therefore reducing serum concentrations) Any significant medical disease(s), laboratory abnormalities or condition(s) that in the Investigator's judgment could compromise the subject's welfare, ability to communicate with the study staff, complete study activities, or would otherwise contraindicate study participation. Non-English speaking patients Patients who are not able to consent for themselves. pregnant patients (All female patients of childbearing potential are given a pregnancy test prior to any elective surgery at Surgicare. Though acetaminophen is NOT harmful to these patients, they will be excluded given the fact that elective surgery in itself is contraindicated in pregnancy)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kimberly H Babiash, MD
Phone
806-543-6589
Email
kbabiash@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kimberly H Babiash, MD
Official's Role
Principal Investigator
Facility Information:
Facility Name
Surgicare of Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67208
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerry Bassell, MD
Phone
316-685-2207
First Name & Middle Initial & Last Name & Degree
Kimberly H Babiash, MD

12. IPD Sharing Statement

Learn more about this trial

Equality Study of Ofirmev vs Oral Acetaminophen

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