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Low accrual
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The purpose of this study is to examine the effect of early, percutaneous, intra-articular saline lavage on the undiluted synovial fluid microenvironment during the acute phase following intra-articular fracture of the human ankle. We hypothesize that early intervention with percutaneous joint lavage in the first 0-48 hours after injury will attenuate the production of pro-inflammatory cytokines, MMP's and cartilage breakdown products compared to non-lavaged control subjects at the time of surgical fixation.
Saline joint lavage represents a potentially simple, low-risk and minimal-cost intervention which has not been previously studied for the purpose of reducing the post-fracture inflammatory burden in human subjects. Open joint lavage at the time of definitive surgical fixation is within the standard of care, but typically occurs greater than 10 days after injury by which time cartilage degradation has already begun. Early, saline lavage during initial presentation to the emergency department may theoretically alter the progression of the intra-articular inflammatory response by evacuating the bulk of the developing synovial-fluid fracture hematoma.
The vast majority of ankle fractures present to the ER or urgent care within a day of fracture. Moreover, a large subset of these fractures require reduction (fracture setting) that is painful. It is our standard of care to perform an intra-articular lidocaine injection before reduction. We will take advantage of this standard of care needle insertion to the fractured ankle to perform saline joint lavage to diminish this early inflammatory burden. Adult patients presenting to the Duke University Hospital Emergency Department with an intra-articular fracture of the ankle joint between 0-48 hours from the time of injury will be eligible for inclusion. Patients will be randomized into one of two groups: 1) intra-articular saline lavage, vs 2) no intra-articular saline lavage. Intra-articular aspiration of synovial fluid from the injured ankle will occur both at the time of presentation to the emergency department and at the time of surgery. These synovial fluid samples will be analyzed for differences in key pro-inflammatory cytokines, matrix metalloproteinases and cartilage breakdown products to determine if early saline lavage effects the composition of the synovial fluid micro-environment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intra-articular saline lavage | Experimental | Subjects in Group 1 will then undergo saline joint lavage as follows: Subjects will undergo aspiration of the injured ankle joint via the standard anteromedial arthroscopy portal approach. This will be performed with sterile technique using a 16-gauge needle attached to a 10cc syringe. After synovial fluid aspiration, three 10cc syringes will be filled with 10cc of sterile 0.9% normal saline. Normal saline will be injected into the ankle joint and withdrawn from the joint via the existing anteromedial 16 gauge needle. After three rounds of lavage, 10cc of 1% lidocaine without epinephrine will be injected into the joint via the existing anteromedial 16-gauge needle. Subjects will undergo a period of soft tissue rest to allow for the resolution of soft tissue swelling. At the time of surgical fixation subjects will again undergo intra-articular aspiration of the injured ankle joint. |
|
| No intra-articular saline lavage | Active Comparator | Subjects in group 2 will not undergo normal saline lavage. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saline Lavage | Device | Three rounds of 10cc of sterile 0.9% normal saline will be injected into the injured ankle joint and withdrawn from the joint using an anteromedial 16-gauge needle attached to a 10cc syringe. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cytokine Levels at Specific Time Points After Injury | Reported as the total change between baseline and 1 to 2 weeks post-injury. | Baseline (within 24 hours of injury), 1 to 2 weeks post-injury |
| Change in CTX-II (C-telopeptide of Type II Collagen) Level at Specific Time Points After Injury | Reported as the total change between baseline and 1 to 2 weeks post-injury. | Baseline (within 24 hours of injury), 1 to 2 weeks post-injury |
| Change in MMP (Matrix Metalloproteinase) Levels at Specific Time Points After Injury | Reported as the total change between baseline and 1 to 2 weeks post-injury. | Baseline (within 24 hours of injury), 1 to 2 weeks post-injury |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Samuel Adams, MD | Duke Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9062947 | Background | Huch K, Kuettner KE, Dieppe P. Osteoarthritis in ankle and knee joints. Semin Arthritis Rheum. 1997 Feb;26(4):667-74. doi: 10.1016/s0049-0172(97)80002-9. | |
| 17106388 | Background | Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006 Nov-Dec;20(10):739-44. doi: 10.1097/01.bot.0000246468.80635.ef. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Intra-articular Saline Lavage | Subjects in Group 1 will then undergo saline joint lavage as follows: Subjects will undergo aspiration of the injured ankle joint via the standard anteromedial arthroscopy portal approach. This will be performed with sterile technique using a 16-gauge needle attached to a 10cc syringe. After synovial fluid aspiration, three 10cc syringes will be filled with 10cc of sterile 0.9% normal saline. Normal saline will be injected into the ankle joint and withdrawn from the joint via the existing anteromedial 16 gauge needle. After three rounds of lavage, 10cc of 1% lidocaine without epinephrine will be injected into the joint via the existing anteromedial 16-gauge needle. Subjects will undergo a period of soft tissue rest to allow for the resolution of soft tissue swelling. At the time of surgical fixation subjects will again undergo intra-articular aspiration of the injured ankle joint. Saline Lavage: Three rounds of 10cc of sterile 0.9% normal saline will be injected into the injured ankle joint and withdrawn from the joint using an anteromedial 16-gauge needle attached to a 10cc syringe. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Dec 12, 2024 |
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Patients will be randomized into one of two groups: 1) intra-articular saline lavage, vs 2) no intra-articular saline lavage. Intra-articular aspiration of synovial fluid from the injured ankle will occur both at the time of presentation to the emergency department and at the time of surgery.
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Randomization will occur by the opening of pre-prepared envelopes which will be stored in the orthopaedic resident office. Envelopes will be labeled #1-#60. Thirty envelopes will contain a note card labeled "Group 1" and Thirty envelopes will contain a note card labeled "Group 2". Envelopes will be pre-prepared by key study personnel not involved in the consent or randomization process.
| No intra-articular saline lavage | Other | Subjects in group 2 will not undergo normal saline lavage. |
|
| Lidocaine - intra-articular injection | Drug | Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. |
|
| Synovial Fluid Aspiration | Other | Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
|
| 27764893 | Background | Delco ML, Kennedy JG, Bonassar LJ, Fortier LA. Post-traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches. J Orthop Res. 2017 Mar;35(3):440-453. doi: 10.1002/jor.23462. Epub 2016 Nov 8. |
| 15232420 | Background | Buckwalter JA, Brown TD. Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis. Clin Orthop Relat Res. 2004 Jun;(423):7-16. |
| 18511308 | Background | McKinley TO, Tochigi Y, Rudert MJ, Brown TD. The effect of incongruity and instability on contact stress directional gradients in human cadaveric ankles. Osteoarthritis Cartilage. 2008 Nov;16(11):1363-9. doi: 10.1016/j.joca.2008.04.005. Epub 2008 Jun 3. |
| 15615507 | Background | Dirschl DR, Marsh JL, Buckwalter JA, Gelberman R, Olson SA, Brown TD, Llinias A. Articular fractures. J Am Acad Orthop Surg. 2004 Nov-Dec;12(6):416-23. doi: 10.5435/00124635-200411000-00006. |
| 20728882 | Background | Giannoudis PV, Tzioupis C, Papathanassopoulos A, Obakponovwe O, Roberts C. Articular step-off and risk of post-traumatic osteoarthritis. Evidence today. Injury. 2010 Oct;41(10):986-95. doi: 10.1016/j.injury.2010.08.003. |
| 34617803 | Background | Allen NB, Abar B, Danilkowicz RM, Kraus VB, Olson SA, Adams SB. Intra-Articular Synovial Fluid With Hematoma After Ankle Fracture Promotes Cartilage Damage In Vitro Partially Attenuated by Anti-Inflammatory Agents. Foot Ankle Int. 2022 Mar;43(3):426-438. doi: 10.1177/10711007211046952. Epub 2021 Oct 7. |
| 17957084 | Background | Hembree WC, Ward BD, Furman BD, Zura RD, Nichols LA, Guilak F, Olson SA. Viability and apoptosis of human chondrocytes in osteochondral fragments following joint trauma. J Bone Joint Surg Br. 2007 Oct;89(10):1388-95. doi: 10.1302/0301-620X.89B10.18907. |
| 26449389 | Background | Adams SB, Setton LA, Bell RD, Easley ME, Huebner JL, Stabler T, Kraus VB, Leimer EM, Olson SA, Nettles DL. Inflammatory Cytokines and Matrix Metalloproteinases in the Synovial Fluid After Intra-articular Ankle Fracture. Foot Ankle Int. 2015 Nov;36(11):1264-71. doi: 10.1177/1071100715611176. Epub 2015 Oct 8. |
| 28891711 | Background | Adams SB, Reilly RM, Huebner JL, Kraus VB, Nettles DL. Time-Dependent Effects on Synovial Fluid Composition During the Acute Phase of Human Intra-articular Ankle Fracture. Foot Ankle Int. 2017 Oct;38(10):1055-1063. doi: 10.1177/1071100717728234. Epub 2017 Sep 11. |
| 25636786 | Background | Kimmerling KA, Furman BD, Mangiapani DS, Moverman MA, Sinclair SM, Huebner JL, Chilkoti A, Kraus VB, Setton LA, Guilak F, Olson SA. Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. Eur Cell Mater. 2015 Jan 31;29:124-39; discussion 139-40. doi: 10.22203/ecm.v029a10. |
| 24964765 | Background | Furman BD, Mangiapani DS, Zeitler E, Bailey KN, Horne PH, Huebner JL, Kraus VB, Guilak F, Olson SA. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis. Arthritis Res Ther. 2014 Jun 25;16(3):R134. doi: 10.1186/ar4591. |
| FG001 | No Intra-articular Saline Lavage | Subjects in group 2 will not undergo normal saline lavage. No intra-articular saline lavage: Subjects in group 2 will not undergo normal saline lavage. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Intra-articular Saline Lavage | Subjects in Group 1 will then undergo saline joint lavage as follows: Subjects will undergo aspiration of the injured ankle joint via the standard anteromedial arthroscopy portal approach. This will be performed with sterile technique using a 16-gauge needle attached to a 10cc syringe. After synovial fluid aspiration, three 10cc syringes will be filled with 10cc of sterile 0.9% normal saline. Normal saline will be injected into the ankle joint and withdrawn from the joint via the existing anteromedial 16 gauge needle. After three rounds of lavage, 10cc of 1% lidocaine without epinephrine will be injected into the joint via the existing anteromedial 16-gauge needle. Subjects will undergo a period of soft tissue rest to allow for the resolution of soft tissue swelling. At the time of surgical fixation subjects will again undergo intra-articular aspiration of the injured ankle joint. Saline Lavage: Three rounds of 10cc of sterile 0.9% normal saline will be injected into the injured ankle joint and withdrawn from the joint using an anteromedial 16-gauge needle attached to a 10cc syringe. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
| BG001 | No Intra-articular Saline Lavage | Subjects in group 2 will not undergo normal saline lavage. No intra-articular saline lavage: Subjects in group 2 will not undergo normal saline lavage. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Number of fracture lines | Count of Participants | Participants |
| ||||||||||||||||
| Days from injury aspirate to surgical aspirate | Mean | Full Range | days |
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| 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 | Change in Cytokine Levels at Specific Time Points After Injury | Reported as the total change between baseline and 1 to 2 weeks post-injury. | Data for IL-4, IL-8, and IL-10 was only collected on the first 18 participants due to observed effect sizes, concentration distributions, biological relevance to post-traumatic inflammation, and predefined resource constraints. | Posted | Mean | Standard Deviation | pg/mL | Baseline (within 24 hours of injury), 1 to 2 weeks post-injury |
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| Primary | Change in CTX-II (C-telopeptide of Type II Collagen) Level at Specific Time Points After Injury | Reported as the total change between baseline and 1 to 2 weeks post-injury. | Posted | Mean | Standard Deviation | ng/mL | Baseline (within 24 hours of injury), 1 to 2 weeks post-injury |
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| Primary | Change in MMP (Matrix Metalloproteinase) Levels at Specific Time Points After Injury | Reported as the total change between baseline and 1 to 2 weeks post-injury. | Data for MMP-1, MMP-2, MMP-3, MMP-10, and MMP-13 was only collected on the first 18 participants due to observed effect sizes, concentration distributions, biological relevance to post-traumatic inflammation, and predefined resource constraints. | Posted | Mean | Standard Deviation | pg/mL | Baseline (within 24 hours of injury), 1 to 2 weeks post-injury |
|
Up to 2 weeks post-surgery
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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 | Intra-articular Saline Lavage | Subjects in Group 1 will then undergo saline joint lavage as follows: Subjects will undergo aspiration of the injured ankle joint via the standard anteromedial arthroscopy portal approach. This will be performed with sterile technique using a 16-gauge needle attached to a 10cc syringe. After synovial fluid aspiration, three 10cc syringes will be filled with 10cc of sterile 0.9% normal saline. Normal saline will be injected into the ankle joint and withdrawn from the joint via the existing anteromedial 16 gauge needle. After three rounds of lavage, 10cc of 1% lidocaine without epinephrine will be injected into the joint via the existing anteromedial 16-gauge needle. Subjects will undergo a period of soft tissue rest to allow for the resolution of soft tissue swelling. At the time of surgical fixation subjects will again undergo intra-articular aspiration of the injured ankle joint. Saline Lavage: Three rounds of 10cc of sterile 0.9% normal saline will be injected into the injured ankle joint and withdrawn from the joint using an anteromedial 16-gauge needle attached to a 10cc syringe. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG001 | No Intra-articular Saline Lavage | Subjects in group 2 will not undergo normal saline lavage. No intra-articular saline lavage: Subjects in group 2 will not undergo normal saline lavage. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. | 0 | 10 | 0 | 10 | 0 | 10 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Samuel G. Lorentz, MD | Duke University | (919) 684-8111 | samuel.lorentz@duke.edu |
| Feb 11, 2026 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D057072 | Intra-Articular Fractures |
| ID | Term |
|---|---|
| D050723 | Fractures, Bone |
| D014947 | Wounds and Injuries |
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| IL-6 (Interleukin-6) |
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| IL-4 (Interleukin-4) |
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| IL-8 (Interleukin-8) |
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| IL-10 (Interleukin-10) |
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| 0.624 |
Significance set to p < 0.0125 |
| Other |
| IL-6 | t-test, 2 sided | 0.415 | Significance set to p < 0.05 | Other |
| IL-8 | t-test, 2 sided | 0.887 | Significance set to p < 0.0125 | Other |
| IL-10 | t-test, 2 sided | 0.624 | Significance set to p < 0.0125 | Other |
| OG001 | No Intra-articular Saline Lavage | Subjects in group 2 will not undergo normal saline lavage. No intra-articular saline lavage: Subjects in group 2 will not undergo normal saline lavage. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
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| OG001 | No Intra-articular Saline Lavage | Subjects in group 2 will not undergo normal saline lavage. No intra-articular saline lavage: Subjects in group 2 will not undergo normal saline lavage. Lidocaine - intra-articular injection: Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle. Synovial Fluid Aspiration: Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe. |
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