Influence of Naproxen on Heterotropic Bone Formation Following Hip Arthroscopy
Information source: University of Utah
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heterotopic Ossification
Intervention: Naproxen (Drug); placebo (Drug)
Phase: N/A
Status: Active, not recruiting
Sponsored by: University of Utah Official(s) and/or principal investigator(s): Stephen Aoki, M.D., Principal Investigator, Affiliation: University of Utah Orthopedics Center
Summary
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.
Clinical Details
Official title: Influence of Naproxen on Heterotropic Bone Formation Following Hip Arthroscopy
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Number of participants with documented Heterotopic Ossification (HO) in the Naproxen group vs Placebo group
Secondary outcome: Number of participants with adverse events in the Naproxen group vs Placebo group.
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
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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
Locations and Contacts
University of Utah Orthopedics Center, Salt Lake City, Utah 84108, United States
Additional Information
Starting date: January 2012
Last updated: July 16, 2015
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