Clinical trial NCT07006675: Effect of NSAIDs on Union, Opioid Utilization and Pain Management for Tibia Fractures: A Pragmatic, Randomized Controlled Trial
Official title: Effect of NSAIDs on Union, Opioid Utilization and Pain Management for Tibia Fractures: A Pragmatic, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Tibial Fractures
Pain
Keywords: Ibuprofen
Pain Management
Tibia Fracture
IM Nail Fixation
NSAID
Lead sponsor: Major Extremity Trauma Research Consortium
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2025-06-05
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Secondary surgery to promote bone union after 3 months post initial surgery
timeFrame: 1 year
Secondary outcomes:
measure: Opioid Utilization
timeFrame: 1 year
measure: Adverse Effects and Complications
timeFrame: 1 year
measure: Persistent Pain & Pain Inference
timeFrame: 1 year
measure: Physical and Psychosocial Function
timeFrame: 1 year
measure: Radiographic bone union
timeFrame: 1 year
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Eskenazi Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University-Methodist
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland R Adams Cowley Shock Trauma Center
state: Maryland
city: Cambridge
country: United States
facility: Harvard Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin Health
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: Cleveland
country: United States
facility: The MetroHealth System
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary, Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Utah
name: Thomas Higgins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Renan Castillo, PhD
role: PRINCIPAL_INVESTIGATOR
References: