Influence of Naproxen on Heterotropic Bone Formation Following Hip Arthroscopy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Stephen Aoki, University of Utah
ClinicalTrials.gov Identifier:
NCT01539447
First received: January 12, 2012
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

In a brief summary the study would like to evaluate the effectiveness of Naproxen in preventing radiographically detected heterotopic ossification following hip arthroscopy for the treatment of femoroacetabular impingement.


Condition Intervention
Heterotopic Ossification
Drug: Naproxen
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Influence of Naproxen on Heterotropic Bone Formation Following Hip Arthroscopy

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Number of participants with documented Heterotopic Ossification (HO) in the Naproxen group vs Placebo group [ Time Frame: 75 days after surgery ] [ Designated as safety issue: No ]
    The hypothesis is that there will be fewer instances of HO in the Naproxen group compared to the Placebo group.


Secondary Outcome Measures:
  • Number of participants with adverse events in the Naproxen group vs Placebo group. [ Time Frame: Data outcome collected 4 weeks post operatively ] [ Designated as safety issue: No ]
    Adverse events include GI upset, GI bleed, Kidney failure, Drug reactions and Healing problems.


Estimated Enrollment: 342
Study Start Date: January 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Naproxen
• Group 1: Naproxen 500 mg twice daily for three weeks following surgery beginning postoperative day #1
Drug: Naproxen
• Group 1: Naproxen 500 mg twice daily for three weeks following surgery beginning postoperative day #1
Other Name: Naproxen
Placebo Comparator: Placebo
• Group 2: Placebo twice daily for three weeks following surgery beginning postoperative day #1
Drug: placebo
• Group 2: Placebo twice daily for three weeks following surgery beginning postoperative day #1
Other Name: Placebo Control

Detailed Description:

Heterotopic bone formation (HO) is a potentially serious complication of hip surgery. HO, defined as the formation of normal bone in an abnormal soft tissue location, results from alteration in the normal regulation of skeletogenesis. Although most patients remain asymptomatic despite HO development, two articles that included 10,826 patients from 37 studies suggest HO may be associated with substantial compromise of function and range of motion even at low grades.In a large pooled incidence study, HO was estimated to be 43% in 59,121 patients undergoing total hip arthroplasty, and 51% in 998 patients after acetabular trauma.

Few studies have reported on the incidence of HO following hip arthroscopy. However, HO is an increasingly reported complication of arthroscopic treatment for femoroacetabular impingement(FAI). In a comparison of complications following arthroscopic treatment of FAI in 8 case-series, ectopic ossification occurred in up to 6% of cases and accounted for 10 of the 19 reported complications. Additionally, one recent study reported an HO incidence of 33% (5 out of 15 patients) following hip arthroscopy in patients not prophylaxed with NSAID therapy. In our experience, HO occurs at a comparable or higher rate of 10% in those undergoing this procedure. The formation of ectopic ossification is triggered as a result of muscle damage during introduction of hip portals and is potentially augmented by seeding of bone shavings in the soft tissues created during burring of the femoral neck.

Prophylaxis of HO targets the biochemical mechanisms of heterotopic bone formation by: 1) Disrupting inductive signaling pathways, 2) Altering osteoprogenitor cells in target tissues, and 3) Modifying the environment conductive to formation of heteroptic bone. The two mainstays of therapy are low dose radiation treatment and non-steroidal anti-inflammatory medications (NSAIDs). The efficacies of these treatments were found to be equivalent by Burd et al in 166 randomized patients. However, NSAID therapy was shown to be considerably more cost effective with lower rates of morbidity. Large randomized studies have subsequently shown large reductions in the incidence of HO using NSAID therapy in the perioperative period. The Cochrane review of 16 randomized trials in 5000 patients found one-half to two-thirds reduction in HO with indomethacin.Even less potent NSAID therapy has been effective in reducing rates of HO. Fransen et al reported a 30% reduction in HO during the HIPAID trial comparing perioperative ibuprofen with placebo in nearly 1000 patients. The two groups had no statistical difference in functional outcome despite the higher incidence of HO in the prophylaxed group.

While NSAID therapy has been effective in reducing the incidence of HO, it is associated with potentially serious side affects. Fransen et al found 202 GI side effects in a metaanalysis of 4328 patients taking NSAIDs for HO prophylaxis.1 Of these, 138 were minor (e.g. nausea, dyspepsia, diarrhea) and 64 were major (e.g. hematemesis or melena). Overall, there was a 31% increase in the risk of GI side effects among patients taking NSAIDs. Furthermore, NSAID therapy could impair bone and/or soft tissue healing following this. These side affects could negate the benefit of NSAID therapy, especially if HO is asymptomatic in the majority of patients.

We hypothesize that NSAID prophylaxis of HO may have a role in hip arthroscopy for the treatment of femoroacetabular impingement. All NSAIDs tested, with the exception of aspirin, have resulted in significant decreases in the incidence of HO following hip surgery including less potent regimens such as ibuprofen 1200 mg/day. Naproxen offers the advantage of twice daily dosing with similar potency to ibuprofen. It is readily available and inexpensive. Furthermore, in an unpublished series of 50 patients prescribed naproxen following hip arthroscopy for FAI, we have had no cases of HO at 6 month follow up compared to a 5-10% rate in patients who received no prophylaxis. We propose testing our hypothesis that perioperative naproxen will reduce the incidence of HO following hip arthroscopy in a placebo controlled, double-blinded, randomized controlled trial.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient is 18-80 years of age.
  • The patient has provided written informed consent.
  • The patient is scheduled for hip arthroscopy surgery for treatment of FAI
  • The patient has an ASA of I, II, or III.
  • The patients understands the explanation of the protocol.

Exclusion Criteria:

  • The patient has history of a major GI bleeding event
  • The patients has a history of renal impairment or creatinine > 1.5
  • The patient has taken NSAIDs within 48 hours of surgery or in the perioperative period
  • The patient has a history of heterotopic ossification following surgery
  • The patient has a hypersensitivity reaction to Naproxen
  • The patient is undergoing a concomitant procedure in addition to treatment of FAI
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01539447

Locations
United States, Utah
University of Utah Orthopedics Center
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Stephen Aoki, M.D. University of Utah Orthopedics Center
  More Information

No publications provided

Responsible Party: Stephen Aoki, M.D., University of Utah
ClinicalTrials.gov Identifier: NCT01539447     History of Changes
Other Study ID Numbers: 48961
Study First Received: January 12, 2012
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
Hip arthroscopy
Femoroacetabular impingement
Heterotopic ossification
Heterotopic bone formation

Additional relevant MeSH terms:
Ossification, Heterotopic
Pathologic Processes
Naproxen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 01, 2014