NSAIDS Versus Opioids in Acute SER II Ankle Fractures

Pain Management With NSAIDS in Acute Ankle Fractures Type Supination, External Rotation (SER) II: A Prospective Randomized, Single Blinded Controlled Study

This study is being conducted to evaluate whether NSAIDS are more or less effective in bone healing than opioids in acute fracture pain. Participants will be randomized to one of three groups for first line treatment of pain related to the fracture.

Study Overview

• Status: Completed
• Conditions: Ankle Fracture
• Intervention / Treatment: Drug: Ibuprofen; Drug: Acetaminophen/hydrocodone

Detailed Description

Pain management in acute fractures is challenging and influenced by several factors contributing to pain perception. These factors include but are not limited to tissue damage by the local impact, mechanical stress at the fracture ends, and central perception of the noxious stimulus. Tissue damage and mechanical stress leads to inflammation and further to local swelling. Swelling itself is significant contributor in pain development.

Ideal pain management would attack pain development at most sites possible. The current clinical practice in the US applies a derivate of an opioid analgesic combined with acetaminophen, thereby influencing pain development at central perception by the opioid analgesic and acetaminophen and a peripheral analgesic effect of acetaminophen. The exact mechanism of the peripheral effect is not known.

This clinical practice disregards the positive effect of medications influencing the peripheral inflammatory response, namely nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs affect pain development by blocking the synthesis of arachidonic acid metabolites, inhibiting peripheral inflammatory response and central pain perception. The major reason for not applying NSAIDs in the treatment of acute fracture pain is an experimental animal study showing decreased bone healing in relation to NSAID usage.

However, clinical data thus far is inconclusive, whether bone healing is affected in humans and whether NSAIDs should be avoided in the setting of bone fractures.

This proposed study will give an answer whether the usage of NSAIDs in acute fractures has a negative effect on bone healing.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 to < 60
• Isolated ankle fracture type SER II
• Ability to speak and understand English
• BMI< 35

Exclusion Criteria:

• ASA>3
• Previous or acute gastric bleeding
• Renal insufficiency (Creatinine: >1.27mg/dl)
• Liver insufficiency (Child-Pugh-Wert: 10-15)
• Malignant tumor
• Rheumatoid arthritis
• Heart failure (NYHA III-IV)
• High frequency absolute arrhythmia
• Patients with known psychiatric illness
• Coagulopathy
• Asthma
• Function limiting disease of the lower extremity, besides what is mentioned in the inclusion criteria
• Adults unable to consent
• Pregnant women
• Prisoners
• Workers Comp patient
• Early fracture displacement (within first 2 weeks) indicating need for surgery
• Polytrauma
• Concurrent participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ibuprofen 400 mg; Ibuprofen 400 mg po q 8 hours as needed (PRN) for pain. Subjects will receive Norco, 5/525 mg po q 6 hours PRN if pain relief with Ibuprofen is not sufficient.	Drug: Ibuprofen; Ibuprofen 400 mg and 800 mg; Other Names: Motrin
Active Comparator: Ibuprofen 800 mg; Ibuprofen 800 mg po q 8 hours PRN pain. Subjects will receive Norco, 5/525 mg po q 6 hours PRN if pain relief with Ibuprofen is not sufficient.	Drug: Ibuprofen; Ibuprofen 400 mg and 800 mg; Other Names: Motrin
Active Comparator: Norco; Norco (acetaminophen/hydrocodone) 10/325 mg po q 6 hours PRN pain. If pain is not relieved, physician should be contacted.	Drug: Acetaminophen/hydrocodone; Norco 5/325 mg and 10/325 mg; Other Names: Norco

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fracture healing as measured by radiographic evaluation	fracture healing at 12 weeks followup	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain level improvement as measured by VAS score	VAS score	1 week, 2 weeks, 6 weeks, 9 weeks and 12 weeks
functional improvement as measured by AAOS score	AAOS scale	1 weeks, 2 weeks 6 weeks, 9 weeks and 12 weeks

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Robert J Steffner, MD, University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 20, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 14, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Ankle Fractures; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Acetaminophen; Ibuprofen; Hydrocodone; Acetaminophen, hydrocodone drug combination
• Other Study ID Numbers: 656916