Heterotopic Ossification Prophylaxis

Acetabular Fracture Clinical Trial

Official title:

External Beam Radiotherapy as Prophylaxis for Heterotopic Ossification After Surgical Fixation of Acetabular Fractures: a Prospective, Randomized Feasibility Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04867278
• Other study ID #: HP-00093659
• Status: Enrolling by invitation
• Phase: N/A
• Start date: May 9, 2021
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

One complication that can occur after surgery on the acetabulum is the development of bone in abnormal places such as muscle and soft tissues. There is some evidence that a single dose of radiation to the surgical site within 3 days of surgery will prevent this abnormal bone from forming. However, there are no high quality studies proving that radiation works any better than doing nothing at all. The purpose of our study is to determine whether there is a difference in abnormal bone formation after acetabular surgery when patients are treated with external beam irradiation versus no treatment.

Description:

Heterotopic ossification (HO) is a common complication after surgical fixation of acetabular fractures, with incidence rates reported as high as 90%. HO can be a debilitating complication and surgical excision for more severe cases carries a high complication rate. Numerous strategies have been employed to prevent HO formation but results are mixed and the optimal treatment strategy remains controversial. The most common modalities used to prevent HO formation are oral administration of indomethacin or single-dose external beam irradiation therapy (XRT). Despite the common use of indomethacin and observational data to support its use, more recent randomized controlled trials (RCTs) have failed to demonstrate any significant reduction in the incidence of severe HO when patients were administered 6 weeks of indomethacin versus placebo. Similarly, XRT has been shown to be effective against HO formation in smaller observational studies, but there are no adequately powered RCTs to support its use compared to placebo. Given the high incidence, impact on outcomes, and controversy regarding treatment, there remains a need for continued research to determine optimal treatment strategies for HO prophylaxis. While XRT remains standard of care for prophylaxis at many centers, including our own, there are no RCTs to support its use. Given the associated cost and resources, and potential risk even if minor, our study will help determine the feasibility of a larger RCT to help determine if the use of XRT is justified. For this feasibility study, eligible patients will be randomized to XRT versus control. Both arms will receive gluteus minimus debridement in the OR, which is the standard of care at Shock Trauma. If randomized to the treatment group, patients that undergo surgical fixation of an acetabular fracture via a posterior or combined anterior and posterior approach will undergo a single fraction of external beam radiotherapy to the surgical site within 72 hours of surgery. This treatment is currently the standard procedure performed for all patients who undergo a posterior or combined approach at our institution. The control treatment arm will only include gluteus minimus debridement in the OR and will not receive XRT. We will have 30 patients randomized to each group. We will look at consent rate, power, and HO formation on 3 month post-op radiographs.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 60
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult aged 18+ with an acute acetabular fracture
• Indicated for surgical fixation via a posterior or combined anterior and posterior approach

Exclusion Criteria:

• Contraindication to radiotherapy such as history of cancer/RT
• Patients that are getting an acute total hip arthroplasty at the time of fixation of the acetabular fracture
• Not English speaking
• Not a Maryland resident or likely to have difficulty returning for post-op follow up(s) (i.e. homeless, incarceration)

Related Conditions & MeSH terms

• Acetabular Fracture
• Heterotopic Ossification
• Ossification, Heterotopic

Intervention

Procedure:
• External Beam Radiation (XRT)
Patients that undergo surgical fixation of an acetabular fracture will receive debridement and a single fraction of external beam radiotherapy to the surgical site within 72 hours of surgery.
• Debridement
Gluteus minimus debridement in the OR

Locations

Country	Name	City	State
United States	University of Maryland, Shock Trauma Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (5)

Burd TA, Lowry KJ, Anglen JO. Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures. J Bone Joint Surg Am. 2001 Dec;83(12):1783-8. doi: 10.2106/00004623-200112000-00003. Erratum In: J Bone Joint Surg Am 2002 Jan;84-A(1):100. — View Citation

Karunakar MA, Sen A, Bosse MJ, Sims SH, Goulet JA, Kellam JF. Indometacin as prophylaxis for heterotopic ossification after the operative treatment of fractures of the acetabulum. J Bone Joint Surg Br. 2006 Dec;88(12):1613-7. doi: 10.1302/0301-620X.88B12.18151. — View Citation

Matta JM, Siebenrock KA. Does indomethacin reduce heterotopic bone formation after operations for acetabular fractures? A prospective randomised study. J Bone Joint Surg Br. 1997 Nov;79(6):959-63. doi: 10.1302/0301-620x.79b6.6889. — View Citation

Moore KD, Goss K, Anglen JO. Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fractures: a randomised, prospective study. J Bone Joint Surg Br. 1998 Mar;80(2):259-63. doi: 10.1302/0301-620x.80b2.8157. — View Citation

Sagi HC, Jordan CJ, Barei DP, Serrano-Riera R, Steverson B. Indomethacin prophylaxis for heterotopic ossification after acetabular fracture surgery increases the risk for nonunion of the posterior wall. J Orthop Trauma. 2014 Jul;28(7):377-83. doi: 10.1097/BOT.0000000000000049. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Consent rate	Percentage of participants consented to participate in the study out of all eligible participants approached for consent.	Within 24 hours of surgery
Secondary	Comparison of HO formation by HO prophylaxis type (XRT vs no treatment)	Compare post-operative HO formation, defined as a Brooker class I through IV, between patients that received XRT versus no prophylaxis	12 weeks after surgery
Secondary	Comparison of severe HO formation by HO prophylaxis type (XRT vs no treatment)	Compare post-operative severe HO formation, defined as a Brooker class III or IV, between patients that received XRT versus no prophylaxis	12 weeks after surgery