NCT07006675

Brief 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,000

participants targeted

Target at P75+ for phase_3

Timeline
10mo left

Started May 2021

Longer than P75 for phase_3

Geographic Reach
2 countries

14 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress86%
May 2021Mar 2027

Study Start

First participant enrolled

May 26, 2021

Completed
4 years until next milestone

First Submitted

Initial submission to the registry

May 27, 2025

Completed
9 days until next milestone

First Posted

Study publicly available on registry

June 5, 2025

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2026

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

June 5, 2025

Status Verified

May 1, 2025

Enrollment Period

5.5 years

First QC Date

May 27, 2025

Last Update Submit

May 27, 2025

Conditions

Tibial FracturesPain

Keywords

IbuprofenPain ManagementTibia FractureIM Nail FixationNSAID

Outcome Measures

Primary Outcomes (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.

    1 year

Secondary Outcomes (5)

  • Opioid Utilization

    1 year

  • Adverse Effects and Complications

    1 year

  • Persistent Pain & Pain Inference

    1 year

  • Physical and Psychosocial Function

    1 year

  • Radiographic bone union

    1 year

Study Arms (2)

Standard of Care Pain Management with NSAIDs

ACTIVE COMPARATOR

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.

Drug: 600 mg Ibuprofen

Standard of Care Pain Management without NSAIDs

NO INTERVENTION

Control 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.

Interventions

600 mg IbuprofenDRUG

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.

Also known as: Advil, Motrin
Standard of Care Pain Management with NSAIDs

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Eskenazi Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

Indiana University-Methodist

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Maryland R Adams Cowley Shock Trauma Center

Baltimore, Maryland, 21201, United States

RECRUITING

Harvard Medical Center

Cambridge, Massachusetts, 02138, United States

RECRUITING

Hennepin Health

Minneapolis, Minnesota, 55487, United States

RECRUITING

University of Mississippi

Jackson, Mississippi, 39216, United States

RECRUITING

The MetroHealth System

Cleveland, Ohio, 44109, United States

RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

Vanderbilt Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas Health Science Center - Houston

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84108, United States

RECRUITING

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

University of Calgary, Foothills Medical Centre

Calgary, Alberta, Canada

RECRUITING

MeSH Terms

Conditions

Tibial FracturesPainAgnosia

Interventions

Ibuprofen

Condition Hierarchy (Ancestors)

Fractures, BoneWounds and InjuriesLeg InjuriesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsPerceptual DisordersNeurobehavioral ManifestationsNervous System Diseases

Intervention Hierarchy (Ancestors)

PhenylpropionatesAcids, CarbocyclicCarboxylic AcidsOrganic Chemicals

Study Officials

  • Thomas Higgins, MD

    University of Utah

    PRINCIPAL INVESTIGATOR

  • Renan Castillo, PhD

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Higgins, MD

CONTACT

801-870-113thomas.higgins@hsc.utah.edu

Katherine Frey, PhD

CONTACT

kparris1@jhu.edu

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2025

First Posted

June 5, 2025

Study Start

May 26, 2021

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

March 1, 2027

Last Updated

June 5, 2025

Record last verified: 2025-05

Locations

US(13)CA(1)