Clinical trial NCT03749616
Conditions: Distal Radius Fracture
Sponsor: University of Missouri-Columbia
Start date: 2019-01-02; Completion date: 2022-03-24
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are excellent medications for providing pain control in certain patients. There is some data to suggest that NSAIDs can be used to reduce postoperative pain and narcotic use in patients who had undergone carpal tunnel release. There are mixed results about the effect of bone healing in adult patients with broken bones. The investigators hypothesize that NSAID administration in the acute phase of distal radius fracture healing will be non-inferior for pain control and decrease the use of opioid analgesics compared to patients who take acetaminophen for pain control during this same time period. Furthermore, the investigators hypothesize that patients will have similar or better patient reported outcomes, range of motion, and strength with the administration of NSAIDs.

Detailed description:
In the United States, drug overdose deaths and opioid-involved deaths continue to increase, quadrupling since 1999; six out of ten drug overdose deaths involve an opioid. Overdoses from prescription opioids are a driving factor in the 15-year increase in opioid overdose deaths. The amount of prescription opioids sold to pharmacies, hospitals, and doctors' offices has drastically risen, yet there had not been an overall change in the amount of pain that Americans reported. Deaths from prescription opioids-drugs like oxycodone, hydrocodone, and methadone-have more than quadrupled since 1999.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to control both postoperative pain and pain associated with some orthopaedic injuries in children and adults with certain orthopaedic injuries. Further, the use of NSAIDs for pain control has been shown to lessen the use of narcotic pain medications, the adverse effects of which are well known. With the current opioid epidemic, more research is needed to determine strategies to reduce opioid use in patients with orthopaedic injuries. Chapman et al. showed that NSAIDs can be used effectively to reduce postoperative pain and narcotic use in patients who had undergone carpal tunnel release. Although distal radius fractures are one of the most common fractures, no studies have examined the effect of NSAIDs on distal radius fracture pain. The purpose of this study is to compare pain and narcotic pain medication use in patients who have had distal radius fractures in patients who use NSAIDs to those who do not.

To the authors' knowledge, there have been no clinical prospective, randomized studies to evaluate the effect that NSAIDs have on patients with distal radius fractures. The investigators hypothesize that NSAID administration in the acute phase of distal radius fracture healing will be non-inferior for pain control and decrease the use of opioid analgesics compared to patients who take acetaminophen for pain control during this same time period.

Arms: arm 1: Acetaminophen for pain control with dose and frequency of 325mg 1-2 tablets q4-6h hours as needed, Maximum dose 1000mg. Maximum amount per day: 3g/day.

Oxycodone 5mg 1-2 tablets q4-6 hours will be available as needed for breakthrough pain. arm 2: NSAID administered ibuprofen 400-800 mg, up to three times a day and acetaminophen with dose and frequency of 325mg 1-2 tablets q4-6h hours as needed, Maximum dose 1000mg. Maximum amount per day: 3g/day as needed for pain control.

Oxycodone 5mg 1-2 tablets q4-6 hours will be available for breakthrough pain.
Interventions: intervention 1: Ibuprofen intervention 2: Acetaminophen
Intervention descriptions: intervention 1: NSAID Group - will be administered ibuprofen 400-800 mg, up to three times a day as needed for pain control intervention 2: Control Group - will be administered acetaminophen for pain control with dose and frequency of 325mg 1-2 tablets q4-6h hours as needed, Maximum dose 1000mg. Maximum amount per day: 3g/day.

Protocol documents:
Prot_SAP_000.pdf: 
MU IRB version:  3/26/2014 
 Page 1 of 9 
 
Date: 03/24/2022 
Version Number:  3.0 
Principal Investigator: Daniel London, MD 
Application Number: 2009129 
Application Title: Effect of NSAID Use on Pain and Opioid Consumption Following Distal Radius Fracture: A 
Prospective, Randomized Study 
 
 
 
 
 
Effect of NSAID Use on Pain and Opioid Consumption Following Distal Radius 
Fracture: A Prospective, Randomized Study 
 
 
 
 
Principal Investigator: 
Daniel London, MD 
Missouri Orthopaedic Institute 
1100 Virginia Ave 
Columbia, MO 65212  
 
Resident Investigators: 
John Weitlich 
PGY-3 Orthopaedic Surgery Resident 
University of Missouri-Columbia School of Medicine 
 
Paul Hutchinson 
PGY-3 Orthopaedic Surgery Resident 
University of Missouri-Columbia School of Medicine 
 


MU IRB version:  3/26/2014 
 Page 2 of 9 
 
 
Table of Contents: 
 
STUDY SCHEMA 
1 
Abstract 
2 
Objectives 
3 
Background 
4 
Inclusion/Exclusion Criteria 
5 
Drugs 
6 
Enrollment/Randomization 
7 
Study Procedures 
8 
Study Statistics 
9 
Risks 
10 
Benefits 
11 
Costs 
12 
References 
 
 


MU IRB version:  3/26/2014 
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1. Abstract 
In the United States, drug overdose deaths and opioid-involved deaths continue to increase, 
quadrupling since 1999; six out of ten drug overdose deaths involve an opioid1,2. Overdoses 
from prescription opioids are a driving factor in the 15-year increase in opioid overdose 
deaths. The amount of prescription opioids sold to pharmacies, hospitals, and doctors’ offices 
has drastically risen, yet there had not been an overall change in the amount of pain that 
Americans reported1,3. Deaths from prescription opioids—drugs like oxycodone, 
hydrocodone, and methadone—have more than quadrupled since 19994. 
 
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to control both postoperative 
pain and pain associated with some orthopaedic injuries in children and adults with certain 
orthopaedic injuries5–9. Further, the use of NSAIDs for pain control has been shown to lessen the 
use of narcotic pain medications, the adverse effects of which are well known5,9–11. With the current 
opioid epidemic, more research is needed to determine strategies to reduce opioid use in patients 
with orthopaedic injuries. Chapman et al. showed that NSAIDs can be used effectively to reduce 
postoperative pain and narcotic use in patients who had undergone carpal tunnel release12. Although 
distal radius fractures are one of the most common fractures, no studies have examined the effect of 
NSAIDs on distal radius fracture pain. The purpose of this study is to compare pain and narcotic 
pain medication use in patients who have had distal radius fractures in patients who use NSAIDs to 
those who do not. 
 
To the authors’ knowledge, there have been no clinical prospective, randomized studies to 
evaluate the effect that NSAIDs have on patients with distal radius fractures. We hypothesize 
that NSAID administration in the acute phase of distal radius fracture healing will be non-
inferior for pain control and decrease the use of opioid analgesics compared to patients who 
take acetaminophen for pain control during this same time period. Furthermore, we 
hypothesize that patients will have similar or better patient reported outcomes, range of 
motion, and strength with the administration of NSAIDs.  
 
2. Objectives 
Primary Aims:   
1. To compare postoperative pain of skeletally mature patients with distal radius fractures 
administered NSAIDs and acetaminophen for pain control versus those administered 
acetaminophen for pain control.  
2. To compare the need for narcotic pain medication for breakthrough pain in patients given 
NSAIDs and acetaminophen for pain control as compared to patients given acetaminophen 
for pain control.  
 
Secondary Aims:   
1. To evaluate patient reported outcome scores, range of motion, strength, and complications 
in patients given NSAIDs and acetaminophen for pain control as compared to patients 
given acetaminophen for pain control 
2. To compare the rate of non-union of distal radius fractures at 6 weeks in skeletally mature 
patients administered NSAIDs and acetaminophen for pain control versus those 
administered acetaminophen for pain control.  
 
3. Background  
In the United States, drug overdose deaths and opioid-involved deaths continue to increase, 
quadrupling since 1999; six out of ten drug overdose deaths involve an opioid1,2. Overdoses 
from prescription opioids are a driving factor in the 15-year increase in opioid overdose 
deaths. The amount of prescription opioids sold to pharmacies, hospitals, and doctors’ offices 


MU IRB version:  3/26/2014 
 Page 4 of 9 
has drastically risen, yet there had not been an overall change in the amount of pain that 
Americans reported1,3. Deaths from prescription opioids—drugs like oxycodone, 
hydrocodone, and methadone—have more than quadrupled since 19994. 
 
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to control both postoperative 
pain and pain associated with many orthopaedic injuries in children and adults with certain 
orthopaedic injuries5–9. Further, the use of NSAIDs for pain control has been shown to lessen the 
use of narcotic pain medications, the adverse effects of which are well known5,9–11. With the current 
opioid epidemic, more research is needed to determine strategies to reduce opioid use in patients 
with orthopaedic injuries. Chapman et al. showed that NSAIDs can be used effectively to reduce 
postoperative pain and narcotic use in patients who had undergone carpal tunnel release12. Although 
distal radius fractures are one of the most common fractures, no studies have examined the effect of 
NSAIDs on distal radius fracture pain. The purpose of this study is to compare pain and narcotic 
pain medication use in patients who have had distal radius fractures in patients who use NSAIDs to 
those who do not. 
 
4. Inclusion/Exclusion Criteria 
Inclusion Criteria: 
- 
Age ≥ 18 
- 
Distal radius fracture 
 
Exclusion Criteria: 
- 
Contraindication to NSAID use 
1. Cannot tolerate 
2. Gastritis 
3. Ulcers 
4. Chronic kidney disease stage 4 or higher (i.e. GFR <30ml/min) 
5. Bleeding disorders/thrombocytopenia (platelet count <100,000) 
- 
Inability to take breakthrough medications 
- 
Regular use of NSAIDs 
- 
Regular use of narcotics 
- 
Open fracture 
- 
Other orthopaedic injuries (polytrauma) 
- 
Pathologic fracture 
- 
Previous injury to the bone 
- 
Pregnant or plan to become pregnant 
- 
Unable to sign informed consent 
 
5. Drugs 
a. Ibuprofen, acetaminophen, and oxycodone are used in this study. 
b. These drugs are commonly used for pain control. Ibuprofen and acetaminophen are 
available over the counter. Frequency of dosing is similar for ibuprofen and 
acetaminophen, which will reduce confounding variables for the study. 
c. The drugs used in the study are FDA approved for their use in the study. 
 
6. Enrollment/Randomization 
Enrollment: 
Patients who present to the University of Missouri Health Care Emergency Department (ED) or 
clinic with distal radius fractures will be screened for enrollment in the study. General 
inclusion/exclusion criteria will be used to determine patient eligibility.  All eligible patients 
will be screened when they present to clinic for distal radius fracture.  Patients who meet the 


MU IRB version:  3/26/2014 
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study criteria will be asked to participate in the study by study personnel. The study and all 
associated risks/benefits will be thoroughly explained to them. It will be clearly 
communicated to the patient that their participation is completely voluntary and they can 
withdraw from the study at any time, for any reason, with no effect to their care. The patient 
will be given adequate time to discuss their decision with family and friends, and ask the 
study staff questions. If the patient agrees, they will be asked to review/sign an informed 
consent document.  If the patient signs the consent form, they will be provided with a copy of 
the signed document. We plan 200 subjects to complete the study. To account for attrition, we 
plan to enroll up to 250 patients in this study.       
 
Randomization: 
After informed consent is obtained, all patients who meet eligibility criteria will be 
randomized into one of two groups. Randomization will be achieved by using an excel formula 
to randomize all 250 patients to one of two groups. Randomization envelopes will then be 
labeled 1-250. Inside each envelope will be a piece of paper bearing a group name “NSAID” or 
“Control” depending on which group the subject number was randomized to in the excel 
document.  
 
- 
Group 1:  Control Group – will be administered acetaminophen for pain control with 
dose and frequency of 325mg 1-2 tablets q4-6h hours as needed, Maximum dose 
1000mg. Maximum amount per day: 3g/day.  Oxycodone 5mg 1-2 tablets q4-6 hours 
will be available as needed for breakthrough pain.   
 
- 
Group 2:  NSAID Group – will be administered ibuprofen 400-800 mg, up to three times a 
day and acetaminophen with dose and frequency of 325mg 1-2 tablets q4-6h hours as 
needed, Maximum dose 1000mg. Maximum amount per day: 3g/day as needed for pain 
control. Oxycodone 5mg 1-2 tablets q4-6 hours will be available for breakthrough pain. 
 
7. Study Procedures 
Screening/Randomization Visit: The screening visit will occur in the emergency room or in 
clinic, for every patient who agrees to participate in this study after they sign the consent and 
HIPAA documents, regardless on whether the fracture requires surgical intervention or not. 
All patients participating in this study will be randomized and assigned to either the “NSAID” 
or “Control” groups during this visit. In addition to this the following information will be 
collected: 
• Age  
• Gender 
• Height 
• Weight 
• BMI  
• Comorbidities 
• Smoking status 
• Date of injury 
• Mechanism of injury 
• AO classification of fracture 
• VAS scores 
• Pregnancy Status –  
o For female subjects, pregnancy status will verified by the resident verbally as 
per standard of care.  


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Operative Visit: Only patients clinically indicated to undergo surgery will have an operative 
visit. All fractures will be treated with standard of care in regards to operative treatment with 
volar locking plates with or without radial styloid pin(s). The patients may receive 
perioperative regional anesthesia based on the attending surgeon and anesthesiologist’s 
discretion. Females of childbearing potential will undergo routine care pregnancy testing at 
surgery centers.  
 
At Home: The participants will take ibuprofen or acetaminophen for pain control.  They will 
also be given a prescription for oxycodone for breakthrough pain. The patient will be expected 
to record the patient's pain scores based on a visual analog scale and pain medication usage 
for up to four weeks after discharge from the Emergency Department and up to four weeks 
after surgery, if indicated. 
 
Clinic Visits: The subject will be expected to follow up in clinic at 2 weeks, 6 weeks, 3 months 
and 6 months, and 1 year post-ED discharge or postoperatively. The 6 month and 1 year visit 
will be an online survey only. Each visit is described below. 
- 
2 weeks 
- Visual analog pain scale (VAS) 
- Radiographs of the affected extremity 
- Patient-reported outcome scores (Quick Disabilities of the Arm, Shoulder and 
Hand [QuickDASH], Patient-Reported Outcomes Measurement Information 
System [PROMIS]) 
- Pinch and grip strength 
- Wrist range of motion (ROM) 
- 
6 weeks 
- Radiographs of the affected extremity 
- VAS 
- Patient-reported outcome scores (QuickDASH, PROMIS) 
- Pinch and grip strength 
- Wrist ROM 
- 
3 months 
- Radiographs of the affected extremity, if clinically indicated 
- VAS 
- Patient-reported outcome scores (QuickDASH, PROMIS) 
- Pinch and grip strength 
- Wrist ROM 
- 
6 months (survey only) 
- VAS 
- Patient-reported outcome scores (QuickDASH, PROMIS) 
- 
1 year (survey only) 
- VAS 
- Patient-reported outcome scores (QuickDASH, PROMIS) 
 
 
 
 
 
 
 
 


MU IRB version:  3/26/2014 
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Study Calendar: 
**Operative visit only for subjects with operative distal radius fractures  
 
     X*=email survey only 
 
8. Study Statistics 
Primary outcome variables: 
- 
A medication/pain diary will be collected to determine the number of oxycodone 
tablets used for breakthrough pain and number of ibuprofen or acetaminophen tablets 
- 
Radiographic data will be collected to determine union at 6 weeks 
 
Summary of data to be collected: 
- 
Date of injury 
- 
Age 
- 
Gender 
- 
Height 
- 
Weight 
- 
BMI 
- 
Co-morbidities 
- 
Smoking status 
- 
Mechanism of injury 
- 
AO classification of fracture 
- 
VAS scores 
- 
Grip strength 
- 
ROM 
- 
Outcome scores (QuickDASH, PROMIS) 
- 
Complications 
 
Statistical considerations: 
- 
Sample size and power: Based on previous studies, we have conducted a power 
analysis and determined that the sample size of 200 is sufficient. The 200 total patients 
will be divided into two arms, 100 operative distal radius fractures and 100 non-
operative distal radius fractures. 
- 
Statistical analysis: To evaluate the effectiveness of randomization, patient 
characteristics will be compared between groups using standard statistical tests for 
Procedures 
Randomization 
Operative 
Visit** 
2 
weeks 
6 
weeks 
3 
months 
6 
months 
1 
year 
Visit # 
1 
2 
3 
4 
5 
6 
7 
Obtain informed consent 
X 
 
 
 
 
 
 
Assign Subject # 
X 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
BMI 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Co-Morbidities 
X 
 
 
 
 
 
 
Smoking Status 
X 
 
 
 
 
 
 
Date/Mechanism of Injury 
X 
 
 
 
 
 
 
AO Classification of fracture 
X 
 
 
 
 
 
 
Radiographs of the affected 
extremity 
X 
 
X 
X 
X 
 
 
Pinch and grip strength 
 
 
X 
X 
X 
 
 
Wrist range of motion (ROM) 
 
 
X 
X 
X 
 
 
Pain Assessment (VAS) 
X 
X 
X 
X 
X 
X* 
X* 
QuickDASH 
 
 
X 
X 
X 
X* 
X* 
PROMIS Surveys 
 
 
X 
X 
X 
X* 
X* 
AE/Complications 
X 
X 
X 
X 
X 
X 
X 


MU IRB version:  3/26/2014 
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continuous data. Primary hypothesis of the study will be tested using standard 
statistical tests. 
 
Early stopping rules: 
- 
An interim analysis will be done after 50 patients have been randomized, treated, and 
released from hospital care.  If the data from the interim analysis or from the adverse 
events occurring in the study reveal increased risks to the subjects or clearly 
demonstrate no benefit, then the study will be stopped for reevaluation, and the IRB 
notified immediately. 
 
9. Risks 
a. There are no additional risks associated with this study that are not part of the 
standard-of-care routine risks associated with treatment of these injuries. 
b. These potential risks and/or discomforts associated with routine standard-of-care 
treatment of distal radius fractures and associated pain control can include the 
following: 
i. Constipation 
ii. Confusion 
iii. Nausea 
iv. Vomiting 
v. Abdominal pain 
vi. Dizziness 
vii. Respiratory depression 
viii. Acute renal insufficiency  
ix. Bleeding 
x. Infection 
xi. Nerve or blood vessel injury 
xii. Need for surgery/additional surgery 
xiii. Nonunion/malunion 
c. Breach of Confidentiality Risk: 
i. Because patient data is being collected there is a slight risk of a breach of 
confidentiality. 
d. To reduce this risk, most study data will be maintained in a password protected secure 
database, which only research staff have access to. Any physical study forms (ex. 
consent documents, screening forms, surveys) will be kept in a locked cabinet.  All 
study data will be maintained for the minimum amount of time required by the 
University of Missouri. 
e. Patient safety will be ensured through extensive post-operative monitoring to address 
patient complaints, assess for adequate pain control, monitor fracture healing, and 
allow for the collection of data.  Adverse events will be reported to the IRB per federal 
guidelines.  An interim analysis will be done after 50 patients have been randomized, 
treated, and released from hospital care.  If the data from the interim analysis or from 
the adverse events occurring in the study reveal increased risks to the subjects or 
clearly demonstrate no benefit, then the study will be stopped for reevaluation, and the 
IRB notified immediately. 
f. Study Withdrawal by Patient-Participation in this study is voluntary. If the study 
participant wishes to be withdrawn from the study following consent, they may do so 
by letting the key study personnel know they withdraw their consent. 
 
 
 


MU IRB version:  3/26/2014 
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10. Benefits 
a. The potential benefits of this study lie in determining the effect, if any, that NSAIDs 
have on acute distal radius fracture healing in regards to rate of non-union or delayed 
union.  If the study’s hypothesis is correct, that the use of NSAIDs for pain control in 
acute distal radius fractures does not delay bone healing, this will offer an option for 
physicians to utilize that avoids the undesirable side effects of narcotic pain 
medications such as nausea, vomiting, constipation and sedation. 
b. This project will help the medical community understand how the use of NSAIDs effect 
pain and opioid consumption following distal radius fractures. Information gained 
from this research project may help guide future practice protocols. 
 
11. Costs 
a. There is no additional cost to the patient 
b. The patient will not be paid for participation in the study 
 
References 
1.  
Centers for Disease Control and Prevention . Morbidity and Mortality Weekly Report. Vol 60.; 
2011. doi:10.4269/ajtmh.15-0382. 
2.  
Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths — 
United States, 2010–2015. MMWR Morb Mortal Wkly Rep. 2016;65(5051):1445-1452. 
doi:10.15585/mmwr.mm655051e1. 
3.  
Daubresse M, Chang H-Y, Yu Y, et al. Ambulatory diagnosis and treatment of nonmalignant pain 
in the United States, 2000-2010. Med Care. 2013;51(10):870-878. 
doi:10.1097/MLR.0b013e3182a95d86. 
4.  
CDC WONDER. https://wonder.cdc.gov/. Accessed September 27, 2017. 
5.  
Drendel AL, Gorelick MH, Weisman SJ, Lyon R, Brousseau DC, Kim MK. A Randomized Clinical 
Trial of Ibuprofen Versus Acetaminophen With Codeine for Acute Pediatric Arm Fracture Pain. 
Ann Emerg Med. 2009;54(4):553-560. doi:10.1016/j.annemergmed.2009.06.005. 
6.  
Koller DM, Myers AB, Lorenz D, Godambe SA. Effectiveness of Oxycodone, Ibuprofen, or the 
Combination in the Initial Management of Orthopedic Injury-Related Pain in Children. Nursing 
(Lond). 2007;23(9):627-633. 
7.  
Monzon DG, Vazquez J, Jauregui JR, Iserson K V. Pain treatment in post-traumatic hip fracture 
in the elderly: Regional block vs. systemic non-steroidal analgesics. Int J Emerg Med. 
2010;3(4):321-325. doi:10.1007/s12245-010-0234-4. 
8.  
Neri E, A M, Minen F, et al. Sublingual ketorolac versus sublingual tramadol for moderate to 
severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial. Arch 
Dis Child. 2013;98(9):721-724. doi:10.1136/archdischild-2012-303527. 
9.  
Poonai N, Bhullar G, Lin K, et al. Oral administration of morphine versus ibuprofen to manage 
postfracture pain in children: A randomized trial. Cmaj. 2014;186(18):1358-1363. 
doi:10.1503/cmaj.140907. 
10.  
Bayouth L, Safcsak K, Cheatham ML, Smith CP, Birrer KL, Promes JT. Early intravenous 
ibuprofen decreases narcotic requirement and length of stay after traumatic rib fracture. Am 
Surg. 2013;79(11):1207-1212. 
11.  
Cassinelli EH, Dean CL, Garcia RM, Furey CG, Bohlman HH. Ketorolac Use for Postoperative 
Pain Management Following Lumbar Decompression Surgery: A Prospective, Randomized, 
Double-Blinded, Placebo-Controlled Trial. Spine (Phila Pa 1976). 2008;33(12):1313-1317. 
doi:10.1097/BRS.0b013e31817329bd. 
12.  
Chapman T, Kim N, Maltenfort M, Ilyas AM. Prospective Evaluation of Opioid Consumption 
Following Carpal Tunnel Release Surgery. Hand. 2017;12(1):39-42. 
doi:10.1177/1558944716646765.