Pilot RCT Local Gentamicin for Open Tibial Fractures in Tanzania

Open Tibia Fracture Clinical Trial

— pGO-Tibia  

Official title:

A Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin Versus Saline in Open Tibia Fractures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03559400
• Other study ID #: 17-23950
• Secondary ID: K23AR079044
• Status: Completed
• Phase: N/A
• Start date: November 19, 2019
• Est. completion date: September 15, 2021

Study information

• Verified date: December 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 15, 2021
• Est. primary completion date: September 15, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients age 18 or older

2. Diagnosis of an acute open tibial shaft fracture meeting the following criteria:

1. AO/OTA Type 42

2. Primarily closable wound

3. Type I, II, or IIIA Gustilo- Anderson (GA) Classification

Exclusion Criteria:

1. Time from injury to presentation > 48 hours

2. Time from injury to surgery >7 days

3. History of Aminoglycoside allergy

4. GA IIIB or IIIC open fractures

5. Bilateral open tibial fractures

6. Severe brain (GCS<12) or spinal cord injury

7. Severe vascular injury

8. Sustained severe burns (>10% total body surface area (TBSA) or >5% TBSA with full thickness or circumferential injury)

9. Pathologic fracture

10. History of active limb infection, ipsilaterally

Related Conditions & MeSH terms

• Fractures, Bone
• Open Tibia Fracture
• Tibial Fractures

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Tanzania	Muhimbili Orthopaedic Institute	Dar Es Salaam

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Muhimbili Orthopaedic Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Indirect Medical Costs	Indirect (time) costs, such as lost productivity, will be measured using the Work Productivity and Activity Impairment questionaire (WPAI)	1 year
Other	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
Other	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
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.	Baseline
Primary	Rate of Retention	The percentage of patients completing 1 year follow up relative to the total number of 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: fistula, sinus or wound breakdown; purulent drainage from the wound or presence of pus during surgery; phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; presence of microorganisms in deep tissue taken during an operative intervention, as seen on histopathological examination.; All primary events will be reviewed by a masked adjudication committee comprised of 3 non-treating fellowship-trained orthopaedic trauma surgeons.	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.	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).	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.	1 year
Secondary	Occurrence of Nonunion	Nonunion is a binary variable defined by the following criteria: any unplanned reoperation for promotion of bone healing; OR; mRUST<=10 AND either: FIX-IT score <=11 at 12-month follow-up OR recommendation by treating surgeon for nonunion repair surgery	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.	1 year