Clinical trial NCT03559400: Pilot RCT Local Gentamicin for Open Tibial Fractures in Tanzania
Official title: A Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin Versus Saline in Open Tibia Fractures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Open Tibia Fracture
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Muhimbili Orthopaedic Institute
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2018-06-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Enrollment
timeFrame: Baseline
measure: Rate of Retention
timeFrame: 1 year
measure: Occurrence of Fracture-related Infection (FRI)
timeFrame: 1 year
Secondary outcomes:
measure: Euro-Qol 5 Dimensions (EQ-5D)
timeFrame: 1 year
measure: Modified Radiographic Union Scale for Tibial Fractures (mRUST) Score
timeFrame: 1 year
measure: Function Index for Trauma (FIX-IT) Score
timeFrame: 1 year
measure: Occurrence of Nonunion
timeFrame: 1 year
measure: Occurrence of Fracture-related Reoperation
timeFrame: 1 year
Other outcomes:
measure: Direct Medical Costs
timeFrame: 1 year
measure: Indirect Medical Costs
timeFrame: 1 year
measure: C-Reactive Protein Level
timeFrame: 6 weeks
measure: Microbiology of FRI
timeFrame: 1 year
Locations:
city: Dar Es Salaam
country: Tanzania
facility: Muhimbili Orthopaedic Institute
Study officials:
affiliation: University of California, San Francisco
name: David Shearer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.