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Tibial FracturesPhase 3NSAIDNCT07006675

Effect of NSAIDs on Union, Opioid Utilization and Pain Management for Tibia Fractures: A Pragmatic, Randomized Controlled Trial

A Phase 3 study testing 600 mg Ibuprofen in people with Tibial Fractures and Pain, run by Major Extremity Trauma Research Consortium at 14 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Two arm, pragmatic, randomized controlled multicenter Phase III noninferiority trial evaluating the efficacy of standard pain management without NSAIDs (Group 1) vs. standard pain management plus up to 6 weeks of NSAIDs (Group 2) in the treatment of tibial shaft fractures. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Tibial Fractures, Pain
What is being tested?
600 mg Ibuprofen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,000 participants
Where
14 sitesin 2 countries
Study dates
26 May 2021to Mar 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All patients with open (Grade I, II, of IIIa) or closed tibia fractures treated with a nail.
  • Patients 18-80 years old inclusive.
  • Patients able to be followed at a METRC facility for at least 12 months following injury

Who cannot join

  • Patient unable to provide informed consent
  • Patients who are current - intravenous drug user.
  • Patients with a history of allergy to the study drugs.
  • Patients unable to swallow oral medications or without functioning GI tract.
  • Patients with a history of gastrointestinal bleeds or gastric perforation.
  • Patients with a history of stroke or heart attack.
Show all 15Show fewer
  • Patients requiring an aspirin or NSAID regimen except for low dose aspirin, 81mg.
  • Patients with any bleeding disorders.
  • Patients with severe renal failure [GFR:<30]. Patients with moderate renal failure [GFR: 30-59] may participate in the study at a modified dose [see section 8.6 for defined modified dose].
  • Patients undergoing daily treatment with systemic glucocorticoids before surgery.
  • Patients likely to have severe problems maintaining follow-up, including patients diagnosed with a severe psychiatric conditions, patients who live too far outside the hospital's catchment area, patients who are incarcerated and patients who have unstable housing situations.
  • Patients with a GCS <15 at discharge.
  • Patients with a closed head injury that precludes NSAIDS.
  • Patients who are pregnant or lactating at time of screening
  • Patients with a bone graft procedure planned for a future date at the time of initial definitive fixation surgery.

Trial locations and contacts

14 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Thomas Higgins, MD contact

801-870-113

thomas.higgins@hsc.utah.edu

Katherine Frey, PhD contact

kparris1@jhu.edu

14 sites in 2 countries

United States13 sites, 13 recruiting

  • University of Maryland R Adams Cowley Shock Trauma Center

    Baltimore, Maryland, 21201

    Yasmin Degani, ydegani@umoa.umm.edu

    Robert O'Toole, MD

    Recruiting

  • Harvard Medical Center

    Cambridge, Massachusetts, 02138

    Michael Weaver, MD

    Recruiting

  • The MetroHealth System

    Cleveland, Ohio, 44109

    Nicholas Romeo, MD

    Recruiting

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

    Greg Gaski, MD

    Recruiting

  • University of Texas Health Science Center - Houston

    Houston, Texas, 77030

    Sterling Boutte, Sterling.Boutte@uth.tmc.edu

    Stephen Warner, MD

    Recruiting

  • Eskenazi Hospital

    Indianapolis, Indiana, 46202

    Karl Shively, MD

    Recruiting

  • Indiana University-Methodist

    Indianapolis, Indiana, 46202

    Lauren Hill, BS, hilllc@iu.edu

    Brian Mullis, MD

    Recruiting

  • University of Mississippi

    Jackson, Mississippi, 39216

    Patrick Bergin, MD

    Recruiting

  • University of Wisconsin

    Madison, Wisconsin, 53705

    Chris Domes, MD

    Recruiting

  • Hennepin Health

    Minneapolis, Minnesota, 55487

    Olutayo Alese, 612-873-4634, olutayo.alese@hcmed.org

    Andrew Schmidt, MD

    Recruiting

  • Vanderbilt Medical Center

    Nashville, Tennessee, 37203

    Karen Trochez, karen.m.trochez@vumc.org

    William Obremskey, MD

    Recruiting

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

    Gregory Altman, MD

    Recruiting

  • University of Utah

    Salt Lake City, Utah, 84108

    Thomas Higgins, MD

    Recruiting

Other trials in United States

Canada1 site, 1 recruiting

  • University of Calgary, Foothills Medical Centre

    Calgary, Alberta

    Prim Schneider, MD, prism.schneider@gmail.com

    Prism Schneider, MD

    Recruiting

Other trials in Canada

About this study

Two arm, pragmatic, randomized controlled multicenter Phase III noninferiority trial evaluating the efficacy of standard pain management without NSAIDs (Group 1) vs. standard pain management plus up to 6 weeks of NSAIDs (Group 2) in the treatment of tibial shaft fractures.

Read the detailed description

The proposed study is a two arm, pragmatic, randomized controlled multicenter Phase III noninferiority trial. We will randomize patients with diaphyseal tibia fractures treated with intramedullary (IM) nail into two treatment arms. The control group will receive standard pain management with no NSAIDs. The treatment intervention group will receive standard pain management plus up to six weeks of NSAIDs (3 weeks of prescribed medication followed by 3 weeks of medication PRN). Our hypothesis is that pain management using up to 6 weeks of NSAIDs will result in improved pain control and lower opioid consumption but demonstrate non-inferior levels of complications compared to standard of care pain management. The aim of the study is to:

Specific Aim: Evaluate the effect of standard pain management without NSAIDs (Group 1) vs. standard pain management plus up to 6 weeks of NSAIDs (Group 2) in the treatment of tibial shaft fractures.

Primary Hypothesis: When compared to patients who received standard of care pain management, patients treated with up to 6 weeks of NSAIDs will have noninferior rates of surgery for nonunion at one year.

Secondary Hypotheses: When compared to patients who received standard of care pain management without NSAIDs, patients treated with up to 6 weeks of NSAIDs will benefit from (1) reduced opioid utilization; (2) reduced levels of persistent pain; (3) reduced pain interference; (4) improved functional outcomes; (5) noninferior rates of analgesic treatment related side effects; and (6) noninferior rates of radiographic union.

Being tested
600 mg Ibuprofen
Keywords
Ibuprofen, Pain Management, Tibia Fracture, IM Nail Fixation, NSAID
Medical subject headings
Tibial Fractures, Pain, Agnosia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 600 mg IbuprofenDrug

    Also called Advil, Motrin

    Treatment patients will receive oral ibuprofen 600 mg three times a day (tid) for up to six weeks. Clinicians in this group may use whatever further analgesia they desire, excluding NSAIDs. For patients who have a clinical concern regarding NSAID and prophylactic anticoagulation, the treating physician may consider prescribing misoprostol.

Study groups in NCT07006675
Study groupRoleWhat they receive
Standard of Care Pain Management with NSAIDsActive comparatorTreatment patients will receive oral ibuprofen 600 mg three times a day (tid) for up to six weeks. Clinicians in this group may use whatever further analgesia they desire, excluding NSAIDs. For patients who have a clinical concern regarding NSAID and prophylactic anticoagulation, the treating physician may consider prescribing misoprostol.
Receives: Drug: 600 mg Ibuprofen
Standard of Care Pain Management without NSAIDsNo interventionControl patients will receive standard of care pain medication regimen and may not use NSAIDs. Clinicians in this group may use whatever further analgesia they desire, excluding NSAIDs.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Secondary surgery to promote bone union after 3 months post initial surgery

    Bone nonunion will be assessed by the presence of a secondary surgery to promote union after 3 months and up to 12 months post definitive fixation surgery. Non-prophylactic secondary surgery to promote union will be considered evidence of nonunion. Each case will be independently reviewed by members of the METRC Central Adjudication Committee and if at least 2 members agree with the assessment of secondary surgery to promote union, no further review will be necessary. The METRC Central Adjudication Committee will convene to discuss the cases for which there is disagreement regarding non-union assessment.

    Measured: 1 year

Secondary outcomes (5)

  1. Opioid Utilization

    Opioid utilization will be recorded in two ways: Opiate pain medicine prescribed by the treating provider as well as self -reported opiate use by the study subjects.

    Measured: 1 year

  2. Adverse Effects and Complications

    Adverse effects and complications of ibuprofen include, in addition to nonunion, wound closure complications, bleeding complications, as well as pain treatment related adverse effects. Adverse effects include nausea, vomiting, dizziness, headaches, renal impairment, platelet inhibition and angioedema. In addition, on 7/9/15 the FDA released an announcement related to the risks of NSAIDS entitled, "FDA Drug Safety Communication: FDA strengthens warning that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes". 45 Consequently, consent forms for this study will include the required language and participants will be assessed for these cardiovascular outcomes.

    Measured: 1 year

  3. Persistent Pain & Pain Inference

    The BPI (Brief Pain Inventory) is a widely used, 15-item measure of pain intensity and interference with daily life and will be assessed at baseline, 3, 6, and 12 months post definitive fixation surgery. It has been extensively validated in both English and Spanish, and also includes questions about pain treatments and the effectiveness of these treatments.46 The BPI pain intensity domain is compatible with the IMMPACT guidelines for assessing pain in clinical trials and the FDA Guidance for Industry on the use of Patient-Reported Outcome Measures. In addition to the BPI instrument, pain inference will be collected using the Patient Report Outcomes Measurement Information System (PROMIS) as described below.

    Measured: 1 year

  4. Physical and Psychosocial Function

    Self -Reported Measures of Physical and Psychosocial Function will be assessed at baseline, 3, 6, and 12 months post definitive fixation surgery using the Patient Report Outcomes Measurement Information System (PROMIS) Computer Adaptive Test (CAT) item banks, a product of the NIH Roadmap for Medical Research. CATs present an advantage over traditional measures in that they target only the most relevant items to each patient and can thus be used to obtain precise measurements with 4-6 items, making assessment across multiple domains feasible. CATs can also extend the ceiling and floor of individual domains, potentially enhancing responsiveness. At any visit if a CAT cannot be administered, respondents will instead complete the appropriate short forms associated with the CAT measure.

    Measured: 1 year

  5. Radiographic bone union

    Radiographic union will be based on the modified RUST score44 assessed between 3 months and 12 months after definitive fixation surgery. Radiographic examinations at 3, 6 and 12 months by an adjudication committee comprised of METRC investigators will be evaluated based on AP and lateral x-rays.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2025
  2. Study start26 May 2021
  3. Primary completionDec 2026 (estimated)
  4. Study completionMar 2027 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
1,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07006675
Sponsor's protocol ID
W81XWH-15-2-0058
Acronym
NSAID
Status last verified
May 2025
First submitted
27 May 2025
Last updated
5 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 600 mg Ibuprofen in people with Tibial Fractures and Pain, run by Major Extremity Trauma Research Consortium at 14 sites in 2 countries.

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 15 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: looking for participants now, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Thomas Higgins, MD (801-870-113, thomas.higgins@hsc.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Secondary surgery to promote bone union after 3 months post initial surgery (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07006675.

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 Jun 2025.

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