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

NCT ID: NCT07006675

Last Updated: 2025-06-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-26

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Tibial Fractures Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors

Study Groups

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Standard of Care Pain Management with NSAIDs

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.

Group Type ACTIVE_COMPARATOR

600 mg Ibuprofen

Intervention Type DRUG

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.

Standard of Care Pain Management without NSAIDs

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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600 mg Ibuprofen

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.

Intervention Type DRUG

Other Intervention Names

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Advil Motrin

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Patient unable to provide informed consent
2. Patients who are current - intravenous drug user.
3. Patients with a history of allergy to the study drugs.
4. Patients unable to swallow oral medications or without functioning GI tract.
5. Patients with a history of gastrointestinal bleeds or gastric perforation.
6. Patients with a history of stroke or heart attack.
7. Patients requiring an aspirin or NSAID regimen except for low dose aspirin, 81mg.
8. Patients with any bleeding disorders.
9. Patients with severe renal failure \[GFR:\<30\]. Patients with moderate renal failure \[GFR: 30-59\] may participate in the study at a modified dose \[see section 8.6 for defined modified dose\].
10. Patients undergoing daily treatment with systemic glucocorticoids before surgery.
11. 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.
12. Patients with a GCS \<15 at discharge.
13. Patients with a closed head injury that precludes NSAIDS.
14. Patients who are pregnant or lactating at time of screening
15. Patients with a bone graft procedure planned for a future date at the time of initial definitive fixation surgery.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

Major Extremity Trauma Research Consortium

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Higgins, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Renan Castillo, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Eskenazi Hospital

Indianapolis, Indiana, United States

Site Status RECRUITING

Indiana University-Methodist

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Maryland R Adams Cowley Shock Trauma Center

Baltimore, Maryland, United States

Site Status RECRUITING

Harvard Medical Center

Cambridge, Massachusetts, United States

Site Status RECRUITING

Hennepin Health

Minneapolis, Minnesota, United States

Site Status RECRUITING

University of Mississippi

Jackson, Mississippi, United States

Site Status RECRUITING

The MetroHealth System

Cleveland, Ohio, United States

Site Status RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

University of Texas Health Science Center - Houston

Houston, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status RECRUITING

University of Wisconsin

Madison, Wisconsin, United States

Site Status RECRUITING

University of Calgary, Foothills Medical Centre

Calgary, Alberta, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Thomas Higgins, MD

Role: CONTACT

801-870-113

Katherine Frey, PhD

Role: CONTACT

Facility Contacts

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Lauren Hill, BS

Role: primary

Yasmin Degani

Role: primary

Olutayo Alese

Role: primary

612-873-4634

Karen Trochez

Role: primary

Sterling Boutte

Role: primary

Prim Schneider, MD

Role: primary

Other Identifiers

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W81XWH-15-2-0058

Identifier Type: -

Identifier Source: org_study_id

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