FracturesPhase 4NCT02076321
The Effect of NSAID Use in the Acute Phase of Skeletally Immature Bone Healing: A Prospective Study
A Phase 4 study testing Acetaminophen and Ibuprofen in people with Fractures, run by University of Missouri-Columbia at 1 site in United States.
Trial summary
Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are excellent medications for providing pain control in children with fractures or those who have surgery to correct bony deformity requiring the bone to be cut (osteotomy) and realigned. Read more about this study
- Who is it for?
- Ages Up to 16 years
- Conditions the study is for
- Fractures
- What is being tested?
- Acetaminophen and Ibuprofen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Nov 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- • Male aged 16 years or less or female aged 14 years or less
- Open physis on radiographs
- Fracture undergoing closed treatment or operative treatment or patient undergoing elective osteotomy
Who cannot join
- • Regular use of NSAIDs
- Allergy to NSAIDs
- Inability to take breakthrough medications due side effects or allergy
- Systemic illness
- Renal impairment
- Liver disease
Show all 18Show fewer
- Polytrauma
- Uncontrolled diabetes
- Regular use of corticosteroids
- History of any skeletal dysplasia
- History of neuromuscular disorder
- History of bleeding disorder
- History of liver disorder
- Pathologic fracture
- Closed physes
- Male greater than 16 years old
- Female greater than 14 years old
- Pregnant or possibly pregnant females based on report and last menstrual period
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Missouri Health System
Columbia, Missouri, 65212
About this study
Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are excellent medications for providing pain control in children with fractures or those who have surgery to correct bony deformity requiring the bone to be cut (osteotomy) and realigned. There is some data to suggest that these types of medications can adversely affect bone healing in adult patients with broken bones or those having spine fusion surgery. There is little data with regard to how these medications effect bone healing in children. With this project, the investigators' goal is to determine if NSAIDs delay or otherwise adversely effect bone healing and to demonstrate that these medications adequately control pain in children with broken bones or those who have had an osteotomy.
Read the detailed description
Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in controlling both post-operative pain and pain associated with orthopaedic injuries, particularly in the pediatric population. Additionally, use of NSAIDs for pain control in this setting avoids the use of narcotic pain medications, the adverse effects of which are well known.
Recent research has suggested a possible association between use of NSAIDs and impaired fracture healing in the skeletally mature, or adult, population. Several adult mammal studies have demonstrated inhibition of bony repair with administration of NSAIDs. Yet, other adult animal studies have failed to find the same effect. Clinical data in the adult population is similarly conflicted, with some studies showing an inhibition of bone healing after posterior spinal fusion, while a larger study found no correlation. The data investigating the effects of NSAID use in adults after fracture or osteotomy is even less clear with some studies demonstrating higher rates of non-union with NSAID administration and others finding no significant effect on bone healing.
The research investigating these outcomes in the skeletally immature population is limited; one study compared administration of ketorolac versus normal saline for 7, 14 and 21 days in a juvenile rat model with a stabilized tibia fracture. They found no significant difference in strength, stiffness or histological characteristics of fracture callus between the two groups. Clinical retrospective studies of the pediatric population with regard to use of NSAIDs after posterior spinal fusion have failed to reproduce findings of inhibitory effects on bone healing. Similarly, two retrospective studies found no cases of delayed union or non-union in pediatric patients who received perioperative ketorolac around the time of operative fixation of fractures, or osteotomy. Given these results, the way in which and the degree to which NSAIDs perturb the inflammatory mileu during the acute phase of healing is potentially distinct from the effects on bone healing in the skeletally mature.
There have been no clinical prospective, randomized studies to evaluate the effect, if any, that NSAIDs have on bone healing in the skeletally immature patient population. The investigators hypothesize that NSAID administration in the acute phase of bone healing, whether it be a fracture or osteotomy, will not result in delayed union or non-union as compared to patients who take acetaminophen for pain control during this same time period.
- Conditions
- Fractures
- Being tested
- Acetaminophen, Ibuprofen
- Medical subject headings
- Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Also called Tylenol
acetaminophen for pain control with dose and frequency of 10-15mg/kg/dose, Maximum dose 1000mg. Maximum amount per day: 75mg/kg (not to exceed 4g/day).
IbuprofenDrug
Also called Advil, Motrin
ibuprofen for pain control with dose and frequency 4-10mg/kg/dose. Maximum of 40mg/kg/day, not to exceed 3,200mg/day. Maximum one-time dose of 800mg.
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen | Other | control group Receives: Drug: Acetaminophen |
| NSAID (Ibuprofen) | Other | Study group Receives: Drug: Ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare the Time to Union of Fractures and Osteotomies in Skeletally Immature Patients Administered NSAIDs for Pain Control, Versus Those Administered Acetaminophen for Pain Control.
Measured: The subject will be enrolled/assessed up to 6 months post-injury/osteotomy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2014 (estimated)
- Study startJan 2014
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for FracturesStudies of the same condition, open and under way.
- More trials run by University of Missouri-ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Hoernschemeyer, University of Missouri-Columbia
- Investigators
- Daniel G Hoernschemeyer, MD, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02076321
- Sponsor's protocol ID
- 1207111
- Status last verified
- Jan 2019
- First submitted
- 19 Feb 2014
- Last updated
- 5 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of NSAID Use in the Acute Phase of Skeletally Immature Bone Healing: A Prospective Study
- ClinicalTrials.gov ID
- NCT02076321
- Acronym / sponsor ID
- 1207111
- Conditions
- Fractures
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 3 Mar 2014 (estimated)
- Results
- Posted 2 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are excellent medications for providing pain control in children with fractures or those who have surgery to correct bony deformity requiring the bone to be cut (osteotomy) and realigned. There is some data to suggest that these types of medications can adversely affect bone healing in adult patients with broken bones or those having spine fusion surgery. There is little data with regard to how these medications effect bone healing in children. With this project, the investigators' goal is to determine if NSAIDs delay or otherwise adversely effect bone healing and to demonstrate that these medications adequately control pain in children with broken bones or those who have had an osteotomy.
Detailed description
Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in controlling both post-operative pain and pain associated with orthopaedic injuries, particularly in the pediatric population. Additionally, use of NSAIDs for pain control in this setting avoids the use of narcotic pain medications, the adverse effects of which are well known.
Recent research has suggested a possible association between use of NSAIDs and impaired fracture healing in the skeletally mature, or adult, population. Several adult mammal studies have demonstrated inhibition of bony repair with administration of NSAIDs. Yet, other adult animal studies have failed to find the same effect. Clinical data in the adult population is similarly conflicted, with some studies showing an inhibition of bone healing after posterior spinal fusion, while a larger study found no correlation. The data investigating the effects of NSAID use in adults after fracture or osteotomy is even less clear with some studies demonstrating higher rates of non-union with NSAID administration and others finding no significant effect on bone healing.
The research investigating these outcomes in the skeletally immature population is limited; one study compared administration of ketorolac versus normal saline for 7, 14 and 21 days in a juvenile rat model with a stabilized tibia fracture. They found no significant difference in strength, stiffness or histological characteristics of fracture callus between the two groups. Clinical retrospective studies of the pediatric population with regard to use of NSAIDs after posterior spinal fusion have failed to reproduce findings of inhibitory effects on bone healing. Similarly, two retrospective studies found no cases of delayed union or non-union in pediatric patients who received perioperative ketorolac around the time of operative fixation of fractures, or osteotomy. Given these results, the way in which and the degree to which NSAIDs perturb the inflammatory mileu during the acute phase of healing is potentially distinct from the effects on bone healing in the skeletally mature.
There have been no clinical prospective, randomized studies to evaluate the effect, if any, that NSAIDs have on bone healing in the skeletally immature patient population. The investigators hypothesize that NSAID administration in the acute phase of bone healing, whether it be a fracture or osteotomy, will not result in delayed union or non-union as compared to patients who take acetaminophen for pain control during this same time period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen | Other | Drug: Acetaminophencontrol group |
| NSAID (Ibuprofen) | Other | Drug: IbuprofenStudy group |
Who may qualify
- Ages
- Up to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- • Male aged 16 years or less or female aged 14 years or less
Key exclusion criteria (18 listed)
- • Regular use of NSAIDs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetaminophenAlso: Tylenolacetaminophen for pain control with dose and frequency of 10-15mg/kg/dose, Maximum dose 1000mg. Maximum amount per day: 75mg/kg (not to exceed 4g/day). | Drug | Acetaminophen |
| IbuprofenAlso: Advil, Motrinibuprofen for pain control with dose and frequency 4-10mg/kg/dose. Maximum of 40mg/kg/day, not to exceed 3,200mg/day. Maximum one-time dose of 800mg. | Drug | NSAID (Ibuprofen) |
Primary outcome
Compare the Time to Union of Fractures and Osteotomies in Skeletally Immature Patients Administered NSAIDs for Pain Control, Versus Those Administered Acetaminophen for Pain Control.
Time frame: The subject will be enrolled/assessed up to 6 months post-injury/osteotomy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel G Hoernschemeyer, MD principal investigator
University of Missouri-Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetaminophen and Ibuprofen in people with Fractures, run by University of Missouri-Columbia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare the Time to Union of Fractures and Osteotomies in Skeletally Immature Patients Administered NSAIDs for Pain Control, Versus Those Administered Acetaminophen for Pain Control. (time frame: The subject will be enrolled/assessed up to 6 months post-injury/osteotomy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.