Intra-Articular FracturesNCT05465382
Effect of Early Saline Lavage on Synovial Fluid Composition Following Intra Articular Ankle Fractures
A study testing Saline Lavage, No intra-articular saline lavage and Lidocaine - intra-articular injection in people with Intra-Articular Fractures, run by Duke University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intra-Articular Fractures
- What is being tested?
- Saline Lavage, No intra-articular saline lavage and Lidocaine - intra-articular injection
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jul 2022to 7 May 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subjects (over 18 years of age)
- Must be treated at Duke University Hospital Emergency Department
- Intra-articular fracture of the ankle joint (any fracture of the fibula or tibia in which the fracture line(s) exit into the cartilage surface of the ankle joint)
- Subjects presenting between 0-48 hours from the time of injury
Who cannot join
- Age < 18 y.o.
- Open fracture
- Nonoperatively treated fractures
- Subjects presenting >48 hours from the time of injury
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: The Effect of Early Saline Lavage on Synovial Fluid Composition Following Human Intra-Articular Ankle Fracture
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.
Read the detailed description
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.
- Conditions
- Intra-Articular Fractures
- Being tested
- Saline Lavage, No intra-articular saline lavage, Lidocaine - intra-articular injection, Synovial Fluid Aspiration
- Medical subject headings
- Intra-Articular Fractures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saline LavageDevice
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.
No intra-articular saline lavageOther
Subjects in group 2 will not undergo normal saline lavage.
Lidocaine - intra-articular injectionDrug
Intra-articular injection of 10cc of 1% lidocaine without epinephrine via the existing anteromedial 16-gauge needle.
Synovial Fluid AspirationOther
Aspiration of ankle joint via standard anteromedial approach. Performed using sterile technique using 16-guage needle attached to 10cc syringe.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Saline Lavage; Drug: Lidocaine - intra-articular injection; Other: Synovial Fluid Aspiration |
| No intra-articular saline lavage | Active comparator | Subjects in group 2 will not undergo normal saline lavage. Receives: Other: No intra-articular saline lavage; Drug: Lidocaine - intra-articular injection; Other: Synovial Fluid Aspiration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cytokine Levels at Specific Time Points After Injury
Reported as the total change between baseline and 1 to 2 weeks post-injury.
Measured: 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.
Measured: 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.
Measured: Baseline (within 24 hours of injury), 1 to 2 weeks post-injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study start22 Jul 2022
- Primary completion7 May 2024
- Study completion7 May 2024
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Intra-Articular FracturesStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Adams, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05465382
- Sponsor's protocol ID
- Pro00110537
- Status last verified
- Mar 2026
- First submitted
- 15 Jul 2022
- Last updated
- 14 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 9062947Brown 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.
PubMed 17106388Delco 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.
PubMed 27764893Buckwalter JA, Brown TD. Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis. Clin Orthop Relat Res. 2004 Jun;(423):7-16.
PubMed 15232420McKinley 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.
PubMed 18511308Dirschl 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.
PubMed 15615507Giannoudis 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.
PubMed 20728882Allen 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.
PubMed 34617803Hembree 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.
PubMed 17957084Adams 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.
PubMed 26449389Adams 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.
PubMed 28891711Kimmerling 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.
PubMed 25636786Furman 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.
PubMed 24964765