Pilot RCT Local Gentamicin for Open Tibial Fractures in Tanzania

NCT03559400 | Completed Results DMC

• 2 other identifiers: 17-23950K23AR079044
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Open Tibia Fracture

Outcome Measures

Primary Outcomes (3)

• 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: 1. fistula, sinus or wound breakdown 2. purulent drainage from the wound or presence of pus during surgery 3. phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens 4. 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 Outcomes (5)

• Euro-Qol 5 Dimensions (EQ-5D)

  1 year

• Modified Radiographic Union Scale for Tibial Fractures (mRUST) Score

  1 year

• Function Index for Trauma (FIX-IT) Score

  1 year

• Occurrence of Nonunion

  1 year

• Occurrence of Fracture-related Reoperation

  1 year

Other Outcomes (4)

• Direct Medical Costs

  1 year

• Indirect Medical Costs

  1 year

• C-Reactive Protein Level

  6 weeks

Study Arms (2)

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.

Drug: local gentamicin injection

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.

Drug: placebo saline injection

Interventions

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.

gentamicin injection at fracture site

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.

placebo saline injection at fracture site

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients age 18 or older
• Diagnosis of an acute open tibial shaft fracture meeting the following criteria:
• AO/OTA Type 42
• Primarily closable wound
• Type I, II, or IIIA Gustilo- Anderson (GA) Classification

You may not qualify if:

• Time from injury to presentation \> 48 hours
• Time from injury to surgery \>7 days
• History of Aminoglycoside allergy
• GA IIIB or IIIC open fractures
• Bilateral open tibial fractures
• Severe brain (GCS\<12) or spinal cord injury
• Severe vascular injury
• Sustained severe burns (\>10% total body surface area (TBSA) or \>5% TBSA with full thickness or circumferential injury)
• Pathologic fracture
• History of active limb infection, ipsilaterally

Sponsors & Collaborators

• University of California, San Francisco: lead
• Muhimbili Orthopaedic Institute: collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Muhimbili Orthopaedic Institute

Dar es Salaam, Tanzania

Location

Related Publications (1)

• 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.

  PMID: 33568230 DERIVED

Limitations and Caveats

This feasibility study was predictably underpowered to detect differences in fracture-related infection and other clinically important secondary outcomes.

Results Point of Contact

• Title: David Shearer, MD, MPH, Associate Professor
• Organization: University of California, San Francisco

david.shearer@ucsf.edu

628-206-8812

Study Officials

• David Shearer, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: June 18, 2018
• Study Start: November 19, 2019
• Primary Completion: September 15, 2021
• Study Completion: September 15, 2021
• Last Updated: December 22, 2023
• Results First Posted: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

TA (1)