Trial Outcomes & Findings for Pilot RCT Local Gentamicin for Open Tibial Fractures in Tanzania (NCT NCT03559400)

Results Overview

The number of participants enrolled in the clinical trial per month will be measured to assess feasibility of the definitive clinical trial.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

100 participants

Primary outcome timeframe

Baseline

Results posted on

2023-12-22

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	45	55
Overall Study COMPLETED	36	46
Overall Study NOT COMPLETED	9	9

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Lost to Follow-up	9	7
Overall Study Death	0	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gentamicin Injection at Fracture Site n=45 Participants 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.	Placebo Saline Injection at Fracture Site n=55 Participants 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.	Total n=100 Participants Total of all reporting groups
Age, Continuous	34.9 years STANDARD_DEVIATION 14 • n=45 Participants	32.5 years STANDARD_DEVIATION 11 • n=55 Participants	33.6 years STANDARD_DEVIATION 12 • n=100 Participants
Sex: Female, Male Female	12 Participants n=45 Participants	8 Participants n=55 Participants	20 Participants n=100 Participants
Sex: Female, Male Male	33 Participants n=45 Participants	47 Participants n=55 Participants	80 Participants n=100 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Tanzania	45 participants n=45 Participants	55 participants n=55 Participants	100 participants n=100 Participants
Mechanism of Injury Road Traffic Injury	37 Participants n=45 Participants	47 Participants n=55 Participants	84 Participants n=100 Participants
Mechanism of Injury Fall	2 Participants n=45 Participants	3 Participants n=55 Participants	5 Participants n=100 Participants
Mechanism of Injury Crush Injury	2 Participants n=45 Participants	3 Participants n=55 Participants	5 Participants n=100 Participants
Mechanism of Injury Gunshot	2 Participants n=45 Participants	0 Participants n=55 Participants	2 Participants n=100 Participants
Mechanism of Injury Other	2 Participants n=45 Participants	2 Participants n=55 Participants	4 Participants n=100 Participants

PRIMARY outcome

Timeframe: Baseline

Population: 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.

The number of participants enrolled in the clinical trial per month will be measured to assess feasibility of the definitive clinical trial.

Outcome measures

Outcome measures
Measure	Overall Enrollment n=100 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	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.
Rate of Enrollment	12.5 Participants enrolled per month Interval 7.0 to 17.0	—

PRIMARY outcome

Timeframe: 1 year

Population: 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.

The percentage of patients completing 1 year follow up relative to the total number of participants

Outcome measures

Outcome measures
Measure	Overall Enrollment n=100 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	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.
Rate of Retention	84 Participants	—

PRIMARY outcome

Timeframe: 1 year

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.

Outcome measures

Outcome measures
Measure	Overall Enrollment n=37 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	Placebo Saline Injection at Fracture Site n=46 Participants 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.
Occurrence of Fracture-related Infection (FRI)	9 Participants	7 Participants

SECONDARY outcome

Timeframe: 1 year

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.

Outcome measures

Outcome measures
Measure	Overall Enrollment n=45 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	Placebo Saline Injection at Fracture Site n=55 Participants 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.
Euro-Qol 5 Dimensions (EQ-5D)	0.950 units on a scale from 0 to 1 Standard Deviation 0.101	0.938 units on a scale from 0 to 1 Standard Deviation 0.195

SECONDARY outcome

Timeframe: 1 year

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).

Outcome measures

Outcome measures
Measure	Overall Enrollment n=45 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	Placebo Saline Injection at Fracture Site n=55 Participants 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.
Modified Radiographic Union Scale for Tibial Fractures (mRUST) Score	11.9 score on a scale from 4-16 Standard Deviation 2.9	12.0 score on a scale from 4-16 Standard Deviation 3.1

SECONDARY outcome

Timeframe: 1 year

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.

Outcome measures

Outcome measures
Measure	Overall Enrollment n=45 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	Placebo Saline Injection at Fracture Site n=55 Participants 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.
Function Index for Trauma (FIX-IT) Score	10.9 score on a scale Standard Deviation 2.7	11.2 score on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: 1 year

Nonunion is a binary variable defined by the following criteria: 1. any unplanned reoperation for promotion of bone healing; OR 2. mRUST\<=10 AND either: FIX-IT score \<=11 at 12-month follow-up OR recommendation by treating surgeon for nonunion repair surgery

Outcome measures

Outcome measures
Measure	Overall Enrollment n=45 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	Placebo Saline Injection at Fracture Site n=55 Participants 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.
Occurrence of Nonunion	7 Participants	6 Participants

SECONDARY outcome

Timeframe: 1 year

This binary variable includes reoperation for infection, wound healing, or fracture union, and excludes the removal of implants for prominence/irritation.

Outcome measures

Outcome measures
Measure	Overall Enrollment n=45 Participants Subjects who were enrolled and randomized to either local gentamicin or placebo saline injection.	Placebo Saline Injection at Fracture Site n=55 Participants 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.
Occurrence of Fracture-related Reoperation	3 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Gentamicin Injection at Fracture Site n=45 participants at risk 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.	Placebo Saline Injection at Fracture Site n=55 participants at risk 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.
Renal and urinary disorders Acute Kidney Injury	11.1% 5/45 • Number of events 5 • 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.	7.3% 4/55 • Number of events 4 • 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.
Ear and labyrinth disorders Hearing impairment	0.00% 0/45 • 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.	1.8% 1/55 • Number of events 1 • 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.

Additional Information

David Shearer, MD, MPH, Associate Professor

University of California, San Francisco

Phone: 628-206-8812

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place