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| ID | Type | Description | Link |
|---|---|---|---|
| K23AR079044 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Muhimbili Orthopaedic Institute | OTHER |
| National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | NIH |
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Local application of antibiotics directly to the traumatic wound is a promising strategy for the prevention of infection after open tibia fractures, which are a significant source of disease burden globally, particularly in low-income countries. This pilot study aims to assess feasibility of a randomized controlled trial to measure the effect of locally applied gentamicin on risk of infection for open tibial fractures in Tanzania. If proven effective, local gentamicin would be a highly cost-effective strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries.
This pilot study is being conducted in Dar es Salaam, Tanzania to assess the feasibility of a masked, placebo-controlled, randomized trial to compare local gentamicin injection to saline injection in open tibial shaft fractures. The study will enroll patients within 1 week of injury. The active or placebo agent will be administered during the initial surgical debridement based on a web-based randomization tool. Patients will be followed for 1 year after surgery to assess for the occurrence of fracture-related infection (FRI), a consensus definition of infection after open fracture or insertion of internal fixation to treat fracture. Additional clinical and economic endpoints will also be measured.
Depending on the outcome of the feasibility study, we may undertake a definitive trial to test the effectiveness of local gentamicin to prevent FRI. If proven effective, local gentamicin would impact the clinical care of open fracture patients both in Tanzania and likely in high-income settings as well. These data will also deepen the understanding of the clinical and economic impact of FRI in open fracture populations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| gentamicin injection at fracture site | Experimental | Subjects with an open tibia fracture who receive gentamicin in saline solution administered after closure at the time of initial debridement. |
|
| placebo saline injection at fracture site | Placebo Comparator | Subjects with an open tibia fracture who receive placebo saline solution administered after closure at the time of initial debridement. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| local gentamicin injection | Drug | Treatment includes debridement and administration of the local antibiotic which will consist of 80mg of liquid gentamicin diluted in 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Enrollment | The number of participants enrolled in the clinical trial per month will be measured to assess feasibility of the definitive clinical trial. | Baseline |
| Rate of Retention | The percentage of patients completing 1 year follow up relative to the total number of participants | 1 year |
| Occurrence of Fracture-related Infection (FRI) | The primary outcome for the definitive trial is occurrence of fracture-related infection (FRI), a binary variable. Any of the four following diagnostic criteria are confirmatory for FRI:
All primary events will be reviewed by a masked adjudication committee comprised of 3 non-treating fellowship-trained orthopaedic trauma surgeons. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Euro-Qol 5 Dimensions (EQ-5D) | EuroQol-5 Dimensions (EQ-5D) measures general health status in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The raw score will be translated to a utility score ranging from 0 (death or no health) to 1 (perfect health) on a continuous scale using health-state valuations from Zimbabwe. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Direct Medical Costs | Direct medical costs of treatment (continuous), including medications, personnel, and supplies will be measured for both the intervention and control groups. | 1 year |
| Indirect Medical Costs |
Inclusion Criteria:
Male or female patients age 18 or older
Diagnosis of an acute open tibial shaft fracture meeting the following criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Shearer, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Muhimbili Orthopaedic Institute | Dar es Salaam | Tanzania |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33568230 | Derived | von Kaeppler EP, Donnelley C, Ali SH, Roberts HJ, Ibrahim JM, Wu HH, Eliezer EN, Porco TC, Haonga BT, Morshed S, Shearer DW. A study protocol for a Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin versus Saline in Open Tibia Fractures (pGO-Tibia) in Dar es Salaam, Tanzania. Pilot Feasibility Stud. 2021 Feb 10;7(1):47. doi: 10.1186/s40814-021-00766-7. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Gentamicin Injection at Fracture Site | Subjects with an open tibia fracture who receive gentamicin in saline solution administered after closure at the time of initial debridement. local gentamicin injection: Treatment includes debridement and administration of the local antibiotic which will consist of 80mg of liquid gentamicin diluted in 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
| FG001 | Placebo Saline Injection at Fracture Site | Subjects with an open tibia fracture who receive placebo saline solution administered after closure at the time of initial debridement. placebo saline injection: Treatment includes debridement and administration of the local antibiotic which will consist of 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Gentamicin Injection at Fracture Site | Subjects with an open tibia fracture who receive gentamicin in saline solution administered after closure at the time of initial debridement. local gentamicin injection: Treatment includes debridement and administration of the local antibiotic which will consist of 80mg of liquid gentamicin diluted in 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Rate of Enrollment | The number of participants enrolled in the clinical trial per month will be measured to assess feasibility of the definitive clinical trial. | For pilot trial feasibility aims, the outcomes are presented for all trial participants rather than by arm to match the a priori feasibility targets for the definitive trial. | Posted | Mean | Full Range | Participants enrolled per month | Baseline |
|
|
1 Year
Definitions consistent with clinicaltrials.gov.
All participants were screened for kidney injury using pre and post-operative creatinine levels. Hearing loss and urinary problems were assessed using a standard questionnaire at each follow up.
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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 | Gentamicin Injection at Fracture Site | Subjects with an open tibia fracture who receive gentamicin in saline solution administered after closure at the time of initial debridement. local gentamicin injection: Treatment includes debridement and administration of the local antibiotic which will consist of 80mg of liquid gentamicin diluted in 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment | Mild to moderate acute kidney injury, defined as a 0.3-1.0 above baseline creatinine |
This feasibility study was predictably underpowered to detect differences in fracture-related infection and other clinically important secondary outcomes.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Shearer, MD, MPH, Associate Professor | University of California, San Francisco | 628-206-8812 | david.shearer@ucsf.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 | May 18, 2020 | Dec 20, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 27, 2021 | Jan 6, 2023 | ICF_001.pdf |
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Patients will receive gentamicin in saline solution or placebo saline injection while under anesthesia during the index surgery. Only the local research pharmacist, the UCSF clinical trial manager, and the DSMC will be unmasked.
|
| placebo saline injection | Drug | Treatment includes debridement and administration of the local antibiotic which will consist of 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
|
| Modified Radiographic Union Scale for Tibial Fractures (mRUST) Score | Radiographic healing as measured by the modified Radiographic Union Scale for Tibial fractures (mRUST). mRUST scores each cortex on an AP and lateral radiograph from a score of 1 (no callus) to 4 (remodeled, fracture not visible). Thus, mRUST ranges from 4 (worst healing score) to 16 (best healing score). | 1 year |
| Function Index for Trauma (FIX-IT) Score | Clinical healing of the fracture will be assessed using the Function index for trauma (FIX-IT) score, which evaluates weight bearing and pain in patients with lower extremity fractures. The FIX-IT score is a clinical outcomes assessment measure ranging from 0 to 12 points in two domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points). The maximum score of 12 indicates the highest level of function. | 1 year |
| Occurrence of Nonunion | Nonunion is a binary variable defined by the following criteria:
| 1 year |
| Occurrence of Fracture-related Reoperation | This binary variable includes reoperation for infection, wound healing, or fracture union, and excludes the removal of implants for prominence/irritation. | 1 year |
Indirect (time) costs, such as lost productivity, will be measured using the Work Productivity and Activity Impairment questionaire (WPAI)
| 1 year |
| C-Reactive Protein Level | C-Reactive protein (CRP) is a known inflammatory marker which may show signs of early infection. The value will be measured in all patients and reported at 6 weeks post-surgery. | 6 weeks |
| Microbiology of FRI | For cases undergoing reoperation for which deep tissue cultures are taken, the frequency of each bacterial species will be reported as a percentage of total FRI for both treatment groups. | 1 year |
| BG001 | Placebo Saline Injection at Fracture Site | Subjects with an open tibia fracture who receive placebo saline solution administered after closure at the time of initial debridement. placebo saline injection: Treatment includes debridement and administration of the local antibiotic which will consist of 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. |
| BG002 | Total | Total of all reporting groups |
| 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 | Number | participants |
|
| Mechanism of Injury | Count of Participants | Participants |
|
|
|
| Primary | Rate of Retention | The percentage of patients completing 1 year follow up relative to the total number of participants | For pilot trial feasibility aims, the outcomes are presented for all trial participants rather than by arm to match the a priori feasibility targets for the definitive trial. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Primary | Occurrence of Fracture-related Infection (FRI) | The primary outcome for the definitive trial is occurrence of fracture-related infection (FRI), a binary variable. Any of the four following diagnostic criteria are confirmatory for FRI:
All primary events will be reviewed by a masked adjudication committee comprised of 3 non-treating fellowship-trained orthopaedic trauma surgeons. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Secondary | Euro-Qol 5 Dimensions (EQ-5D) | EuroQol-5 Dimensions (EQ-5D) measures general health status in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The raw score will be translated to a utility score ranging from 0 (death or no health) to 1 (perfect health) on a continuous scale using health-state valuations from Zimbabwe. | Posted | Mean | Standard Deviation | units on a scale from 0 to 1 | 1 year |
|
|
|
| Secondary | Modified Radiographic Union Scale for Tibial Fractures (mRUST) Score | Radiographic healing as measured by the modified Radiographic Union Scale for Tibial fractures (mRUST). mRUST scores each cortex on an AP and lateral radiograph from a score of 1 (no callus) to 4 (remodeled, fracture not visible). Thus, mRUST ranges from 4 (worst healing score) to 16 (best healing score). | Posted | Mean | Standard Deviation | score on a scale from 4-16 | 1 year |
|
|
|
| Secondary | Function Index for Trauma (FIX-IT) Score | Clinical healing of the fracture will be assessed using the Function index for trauma (FIX-IT) score, which evaluates weight bearing and pain in patients with lower extremity fractures. The FIX-IT score is a clinical outcomes assessment measure ranging from 0 to 12 points in two domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points). The maximum score of 12 indicates the highest level of function. | Posted | Mean | Standard Deviation | score on a scale | 1 year |
|
|
|
| Secondary | Occurrence of Nonunion | Nonunion is a binary variable defined by the following criteria:
| Posted | Count of Participants | Participants | 1 year |
|
|
|
| Secondary | Occurrence of Fracture-related Reoperation | This binary variable includes reoperation for infection, wound healing, or fracture union, and excludes the removal of implants for prominence/irritation. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Other Pre-specified | Direct Medical Costs | Direct medical costs of treatment (continuous), including medications, personnel, and supplies will be measured for both the intervention and control groups. | Not Posted | 1 year | Participants |
| Other Pre-specified | Indirect Medical Costs | Indirect (time) costs, such as lost productivity, will be measured using the Work Productivity and Activity Impairment questionaire (WPAI) | Not Posted | 1 year | Participants |
| Other Pre-specified | C-Reactive Protein Level | C-Reactive protein (CRP) is a known inflammatory marker which may show signs of early infection. The value will be measured in all patients and reported at 6 weeks post-surgery. | Not Posted | 6 weeks | Participants |
| Other Pre-specified | Microbiology of FRI | For cases undergoing reoperation for which deep tissue cultures are taken, the frequency of each bacterial species will be reported as a percentage of total FRI for both treatment groups. | Not Posted | 1 year | Participants |
| 0 |
| 45 |
| 0 |
| 45 |
| 5 |
| 45 |
| EG001 | Placebo Saline Injection at Fracture Site | Subjects with an open tibia fracture who receive placebo saline solution administered after closure at the time of initial debridement. placebo saline injection: Treatment includes debridement and administration of the local antibiotic which will consist of 40mL normal saline injected after inserting a 22 gauge needle down to bone after wound closure. The injection will continue until either all 40cc are injected or there is fluid extravasation from the wound. | 2 | 55 | 0 | 55 | 5 | 55 |
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| Hearing impairment | Ear and labyrinth disorders | Systematic Assessment | Hearing impairment reported on screening questionairre |
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| Crush Injury |
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| Gunshot |
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| Other |
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