Trauma Injury
Conditions
Keywords
Immunofluorescence, Orthopaedic, Trauma
Brief summary
This will be a prospective observational trial to better understand the range and variation associated with bone/soft tissue perfusion in fracture patients and examine the relationship between perfusion, measured using quantitative Indocyanine green (ICG) fluorescence and complications such as surgical site infection (SSI), persistent SSI, and fracture nonunion.
Detailed description
This will be a prospective observational trial to better understand the range and variation associated with bone/soft tissue perfusion in fracture patients and examine the relationship between perfusion, measured using quantitative Indocyanine green (ICG) fluorescence and complications such as surgical site infection (SSI), persistent SSI, and fracture nonunion. Primary outcome measure is complication (either infection, recurrent infection or nonunion). Eligible consenting patients will receive standard of care treatment for their fracture or infection including irrigation and debridement of their operative site and/or fracture fixation. After exposure, 0.1 mg/Kg ICG will be injected intravenously and video rate ICG fluorescence images will be acquired 20 seconds before and 4 minutes after the injection, each before and after debridement. A subset of 38 post-fracture complication patients will undergo surgical treatment for their infection in Center of Innovation Surgery (CIS) and have either an intraoperative Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) after exposure but before the ICG injection or a preoperative DCE-MRI. Patients receiving surgery in the CIS will be required to sign an additional CIS-specific consent document. The need for repeat surgical procedure will be left up to the treating surgeon. If repeat procedure is needed, pre- and post-debridement quantitative ICG fluorescence images will be obtained at each procedure. Study participants will be followed at 2 weeks, 6 weeks, 3 months and 6 months from their index study surgery. Complication including index infection, recurrent infection or delaying union/nonunion will be identified at the time of diagnosis and/or during each participants assessment that occurs during routine outpatient clinic visit. Detailed information on the infection including date of diagnosis, participant signs and symptoms, culture test results, method of treatment(s), and date of resolution will be documented. 4/23/2020: Study recruitment temporarily halted due to COVID-19
Interventions
Patients will be administered FDA approved ICG through intravenous injection and imaged by a FDA approved surgical microscope (Pentero or Spy Elite) which is 0.5 meter away from the subject. Both ICG fluorescence and the two imaging systems have been used for routine clinical practice for many years. Figure (a) shows the Schematic sketch of the imaging systems. ICG fluorescence imaging utilizes intravenously injected ICG, which is a fluorescent dye that is FDA-approved for clinical use, illuminated with near-infrared light. The ICG dye is indirectly activated and the dynamic fluorescence due to bone perfusion can be captured by a video rate imaging system.
Sponsors
Dartmouth College
Dartmouth-Hitchcock Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Open Fracture Cohort (Cohort 1) 1. Patients 18 years of age or older. 2. Open extremity fracture. 3. Planned definitive fracture management with external fixation, internal fixation, or joint fusion. 4. Open fracture wound management that includes formal surgical debridement within 72 hours of their injury. 5. Will have all planned fracture care surgeries performed by a participating surgeon or delegate. 6. Provision of informed consent. Established SSI Fracture Cohort (Cohort 2) 1. Patients 18 years of age or older. 2. Extremity fracture. 3. Prior definitive fracture management with external fixation, internal fixation, or joint fusion. 4. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management. 5. Will have all fracture care surgeries performed by a participating surgeon or delegate. 6. Provision of informed consent. Closed Fracture Cohort (Cohort 3) 1. Patients 18 years of age or older. 2. Closed extremity fracture. 3. Planned definitive fracture management with external fixation, internal fixation, or joint fusion. 4. Will have all planned fracture care surgeries performed by a participating surgeon or delegate. 5. Provision of informed consent.
Exclusion criteria
Open Fracture Cohort (Cohort 1) 1. Fracture of the hand. 2. Iodine allergy. 3. Received previous surgical debridement or management of their fracture at a non-participating hospital or clinic. 4. Open fracture managed outside of the participating orthopaedic service. 5. Chronic or acute infection at or near the fracture site at the time of initial fracture surgery. 6. Burns at the fracture site. 7. Incarceration. 8. Expected survival of less than 90 days. 9. Problems, in the judgment of study personnel, with maintaining follow-up with the patient. Established SSI Fracture Cohort (Cohort 2) 1. Fracture of the hand. 2. Iodine allergy. 3. Received previous surgical debridement to manage the SSI. 4. Incarceration. 5. Problems, in the judgment of study personnel, with maintaining follow-up with the patient. Subset: DCE-MRI (Cohort 2-1) 6. the presence of an electronic implant, such as a pacemaker 7. the presence of a metal implant, such as an aneurysm clip 8. the presence of other contraindication(s), as determined by the MRI technologists and radiologists. 9. A history of allergy to iodides 10. A GFR \< 30 ml/min as determined by blood test on the day of NIR/MR imaging, or from lab results within 3 months of DCE-MRI for this study Closed Fracture Cohort (Cohort 3) 1. Fracture of the hand. 2. Iodine allergy. 3. Chronic or acute infection at or near the fracture site at the time of initial fracture surgery. 4. Burns at the fracture site. 5. Incarceration. 6. Expected survival of less than 90 days. 7. Problems, in the judgment of study personnel, with maintaining follow-up with the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients That Complete the Protocol | 1 year | As this is a pilot and feasibility study, the outcome measure is the percent of patients that successfully complete the protocol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Fracture Cohort Patients 18 years of age or older. Open extremity fracture. Planned definitive fracture management with external fixation, internal fixation, or joint fusion. Open fracture wound management that includes formal surgical debridement within 72 hours of their injury. Will have all planned fracture care surgeries performed by a participating surgeon or delegate. Provision of informed consent.
Immunofluorescence Imaging: Patients will be administered FDA approved ICG through intravenous injection and imaged by a FDA approved surgical microscope (Pentero or Spy Elite) which is 0.5 meter away from the subject. Both ICG fluorescence and the two imaging systems have been used for routine clinical practice for many years. Figure (a) shows the Schematic sketch of the imaging systems. ICG fluorescence imaging utilizes intravenously injected ICG, which is a fluorescent dye that is FDA-approved for clinical use, illuminated with near-infrared light. The ICG dye is indirectly activated and the dynamic fluorescence due to bone perfusion can be captured by a video rate imaging system. | 13 |
| Complication Cohort Patients 18 years of age or older. Extremity fracture. Prior definitive fracture management with external fixation, internal fixation, or joint fusion. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management. Will have all fracture care surgeries performed by a participating surgeon or delegate. Provision of informed consent
Immunofluorescence Imaging: Patients will be administered FDA approved ICG through intravenous injection and imaged by a FDA approved surgical microscope (Pentero or Spy Elite) which is 0.5 meter away from the subject. Both ICG fluorescence and the two imaging systems have been used for routine clinical practice for many years. Figure (a) shows the Schematic sketch of the imaging systems. ICG fluorescence imaging utilizes intravenously injected ICG, which is a fluorescent dye that is FDA-approved for clinical use, illuminated with near-infrared light. The ICG dye is indirectly activated and the dynamic fluorescence due to bone perfusion can be captured by a video rate imaging system. | 6 |
| Closed Fracture Cohort Patients 18 years of age or older Closed extremity fracture Planned definitive fracture management with external fixation, internal fixation, or joint fusion.
Provision of informed consent
Immunofluorescence Imaging: Patients will be administered FDA approved ICG through intravenous injection and imaged by a FDA approved surgical microscope (Pentero or Spy Elite) which is 0.5 meter away from the subject. Both ICG fluorescence and the two imaging systems have been used for routine clinical practice for many years. Figure (a) shows the Schematic sketch of the imaging systems. ICG fluorescence imaging utilizes intravenously injected ICG, which is a fluorescent dye that is FDA-approved for clinical use, illuminated with near-infrared light. The ICG dye is indirectly activated and the dynamic fluorescence due to bone perfusion can be captured by a video rate imaging system. | 1 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 1 | 1 |
Baseline characteristics
| Characteristic | Complication Cohort | Closed Fracture Cohort | Open Fracture Cohort | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 1 Participants | 12 Participants | 18 Participants |
| Age, Continuous | 56 years | 56 years | 42 years | 47 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 1 Participants | 12 Participants | 19 Participants |
| Region of Enrollment United States | 6 participants | 1 participants | 13 participants | 20 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 10 Participants | 15 Participants |
| Type of Extremity Fracture Closed Fracture | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Type of Extremity Fracture Fracture with Complication | 6 Participants | 0 Participants | 0 Participants | 6 Participants |
| Type of Extremity Fracture Open Fracture | 0 Participants | 0 Participants | 13 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 6 | 0 / 1 |
| other Total, other adverse events | 0 / 13 | 0 / 6 | 0 / 1 |
| serious Total, serious adverse events | 2 / 13 | 2 / 6 | 0 / 1 |
Outcome results
Primary
Percent of Patients That Complete the Protocol
As this is a pilot and feasibility study, the outcome measure is the percent of patients that successfully complete the protocol.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Fracture Cohort | Percent of Patients That Complete the Protocol | 61.5 percentage of completed patients |
| Complication Cohort | Percent of Patients That Complete the Protocol | 83.3 percentage of completed patients |
| Closed Fracture Cohort | Percent of Patients That Complete the Protocol | 0 percentage of completed patients |
Comparison: No other statistical analysis completed other than percentage of patients completed as reported in the data table section