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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| External Beam Radiation (XRT) with Debridement | Experimental | Patients 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. |
|
| Debridement Alone (Control) | Active Comparator | The control treatment arm will only include gluteus minimus debridement in the OR and will not receive XRT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| External Beam Radiation (XRT) | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Severe HO Formation | Severe HO formation classified as Brooker class III-IV. | 3 months post-op |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Any HO Formation | Any HO formation classified as Brooker class I-IV. | 3 months post-op |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland, Shock Trauma Center | Baltimore | Maryland | 21201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24625922 | Background | 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. | |
| 9393912 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | External Beam Radiation (XRT) With Debridement | Patients 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. 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 |
| FG001 | Debridement Alone (Control) | The control treatment arm will only include gluteus minimus debridement in the OR and will not receive XRT. Debridement: Gluteus minimus debridement in the OR |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | External Beam Radiation (XRT) With Debridement | Patients 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. 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Severe HO Formation | Severe HO formation classified as Brooker class III-IV. | Posted | Count of Participants | Participants | 3 months post-op |
|
Adverse event data was collected over a period of 3 months post-op for each patient.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | External Beam Radiation (XRT) With Debridement | Patients 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. 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Superficial SSI | Infections and infestations | Non-systematic Assessment | Surgical Site Infection (SSI) categorized as superficial. |
A limitation of the current study is the fourteen-patient crossover from the XRT treatment arm to no XRT. These 14 patients were randomized to the XRT group, but did not receive XRT at all, thus crossing over to the no XRT group. Additionally, although the sample size was adequately powered, there were a relatively few number of study events. Lastly, although the study is multicenter, it is only 2 centers.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Adam Boissonneault | Emory University | (404) 616-1000 | adam.boissonneault@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 22, 2021 | Aug 2, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009999 | Ossification, Heterotopic |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003646 | Debridement |
| ID | Term |
|---|---|
| D013514 | Surgical Procedures, Operative |
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| Debridement | Procedure | Gluteus minimus debridement in the OR |
|
| 17159174 | Background | 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. |
| 9546456 | Background | 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. |
| 11741055 | Background | 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. |
| BG001 | Debridement Alone (Control) | The control treatment arm will only include gluteus minimus debridement in the OR and will not receive XRT. Debridement: Gluteus minimus debridement in the OR |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Head Injury | Count of Participants | Participants |
|
| Acetabular fracture dislocation | Count of Participants | Participants |
|
| Associated fracture pattern | Associated fracture patterns include the following: anterior with posterior hemitransverse, posterior-column with posterior-wall, and transverse with posterior-wall. | Count of Participants | Participants |
|
| Surgical Approach: Kocher-Langenbeck | The Kocher-Langenbeck approach is the method for the reduction and fixation of hip fractures that require fixation via a posterior approach. | Count of Participants | Participants |
|
| Surgical Approach: Combined anterior and posterior | A combined anterior and posterior surgical approach to the hip joint is a procedure that allows access to both the front and back of the hip joint. This approach is used for complex arthroplasty and reconstruction, and can be performed with minimal muscle release. | Count of Participants | Participants |
|
| Trochanteric osteotomy | Count of Participants | Participants |
|
| Gluteus minimus muscle debridement | Count of Participants | Participants |
|
| NSAIDS for pain management | Count of Participants | Participants |
|
| Closed suction drain at wound closure | Count of Participants | Participants |
|
| Tranexamic acid used | Count of Participants | Participants |
|
| Mechanical ventilation | Count of Participants | Participants |
|
| OG001 | Debridement Alone (Control) | The control treatment arm will only include gluteus minimus debridement in the OR and will not receive XRT. Debridement: Gluteus minimus debridement in the OR |
|
|
| Secondary | Number of Participants With Any HO Formation | Any HO formation classified as Brooker class I-IV. | Posted | Count of Participants | Participants | 3 months post-op |
|
|
|
| 0 |
| 54 |
| 0 |
| 54 |
| 2 |
| 54 |
| EG001 | Debridement Alone (Control) | The control treatment arm will only include gluteus minimus debridement in the OR and will not receive XRT. Debridement: Gluteus minimus debridement in the OR | 0 | 50 | 0 | 50 | 3 | 50 |
|
| Deep SSI | Infections and infestations | Non-systematic Assessment | Surgical Site Infection (SSI) categorized as deep. |
|
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