Clinical trial NCT03861624: Intramedullary Nailing Versus External Fixation in Open Tibia Fractures in Tanzania
Official title: Intramedullary Nailing Versus External Fixation in the Treatment of Open Tibia Fractures in Tanzania - Results of a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tibial Fractures
Open Fracture of Tibia
Trauma
Keywords: Tibia
Intramedullary nailing
External fixation
Trauma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Wyss Foundation, Inc
name: Doris Duke Charitable Foundation
First posted: 2019-03-04
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose to undertake a randomized, controlled trial which will generate Level 1 evidence concerning optimal fixation methods for the treatment of severe open tibia fractures in Dar es Salaam, Tanzania. The investigators hope to determine the optimal management of severe open tibial fractures in Sub-Saharan Africa in order to reduce long-term disability, limit the economic impact of injury, and avoid resource costs of reoperation. The investigators plan to compare the all-cause reoperation rate for AO/Orthopaedic Trauma Association (OTA) Type 42 open tibial shaft fractures treated with initial intramedullary nailing versus external fixation at Muhimbili Orthopaedic Institute in Dar es Salaam, Tanzania, to compare rates of secondary clinical endpoints including postoperative superficial and deep infection, clinical union, radiographic union, malunion, and health-related quality of life with minimum one year follow-up, and identify prognostic factors related to the patient, injury, or management protocol that impact the reoperation rate, return to work, and health-related quality of life.

Detailed description: The investigators conducted a prospective randomised controlled trial at a tertiary referral hospital in Dar es Salaam, Tanzania from December 17th, 2015 to March 25th, 2017. All open tibia fractures arriving at the hospital emergency room during the enrollment period were screened for inclusion in the study. Inclusion and exclusion criteria are noted later in this submission.All patients who were eligible after clinical screening were offered enrollment in the study and subsequently completed written informed consent in either English or Swahili depending on the patient's preference. The investigation was approved by ethical review boards at the University of California San Francisco (UCSF) and the Tanzanian National Institute for Medical Research (NIMR).

All enrolled participants were taken to the operating room for initial irrigation and debridement using a standardized protocol aiming for debridement within 24 hours of hospital admission. Preoperative ceftriaxone was given as soon as possible after presentation to the emergency department. Following debridement, the primary surgeon determined if the wound was amenable to immediate or delayed primary closure. If amenable to primary closure, the patient was randomized by a site research coordinator to one of two treatments (Intramedullary nailing (IMN) or external fixation (EF))using a centralized web-based electronic randomization tool, Research Electronic Data Capture (REDCap). The study computer analyst developed the REDCap randomization module with input from senior authors. The REDCap randomization module incorporated block randomization to maintain equal patient distribution between each treatment group and to ensure allocation concealment.

Data from a pilot study at the site of our investigation informed sample size calculations, which showed reoperation rates of external fixation and intramedullary nailing of 38% versus 3.8%. However, with longer follow-up and more stringent criteria for a primary event, The investigators used a more conservative effect size of 20% compared to 5%. Using a power of 80% and alpha of 0.05, The investigators calculated the study would require 88 patients in each treatment group (176 total). Accounting for 20% loss to follow up, The investigators estimated a total sample size requirement of 240 patients (120 per group).

Data monitoring was completed by the adjudication committee at 6 month intervals throughout the study duration and prior to final analysis in December, 2018.

Eligibility criteria: Inclusion Criteria:

1. Skeletal maturity
2. AO/OTA 42 open tibia fractures
3. Wound primarily closeable (no flap or delay in closure due to contamination needed)
4. Palpable pedal pulses (no vascular injury sustained)
5. Presentation within 24 hours from injury

Exclusion Criteria:

1. Current injury is a pathologic fracture
2. Sustained bilateral tibia fracture
3. Sustained comminuted femur fracture
4. Sustained severe Traumatic Brain Injury (GCS\<12) \*\*\*
5. Sustained severe spinal cord injury (lower extremity paresis/paralysis)
6. Sustained severe burns (\>10% total body surface area (TBSA) or \>5% TBSA with full thickness or circumferential injury)
7. Prior ipsilateral leg injury requiring surgery
8. Prior or current lower limb deformity or abnormality
9. Unable to complete follow-up visits

Primary outcomes:
measure: Rate of composite, all-cause reoperation
timeFrame: One year of definitive skeletal stabilization
Secondary outcomes:
measure: Rate of superficial infection
timeFrame: Assessed at clinical follow-up appointments at 2, 6, 12, 26, and 52 weeks
measure: Rate of deep infection
timeFrame: Assessed at clinical follow-up appointments at 2, 6, 12, 26, and 52 weeks
measure: Number of participants with clinical nonunion
timeFrame: Assessed at clinical follow-up appointments at 6, 12, 26, and 52 weeks
measure: Number of participants with radiographic nonunion
timeFrame: Assessed at clinical follow-up appointments at 6, 12, 26, and 52 weeks
measure: Number of participants with malunion
timeFrame: Assessed at clinical follow-up appointments at 6, 12, 26, and 52 weeks
measure: Number of participants with implant failure
timeFrame: Assessed at clinical follow-up appointments at 2, 6, 12, 26, and 52 weeks
measure: Health-related quality of life
timeFrame: Assessed at 2, 6, 12, 26, and 52 week time point.
measure: Visual analogue pain score
timeFrame: Assessed at 2, 6, 12, 26, and 52 week time point.
measure: Participant knee range of motion
timeFrame: Assessed at 6, 12, 26, and 52 week time point.
measure: Participant ankle range of motion
timeFrame: Assessed at 6, 12, 26, and 52 week time point.
measure: Participant ability to perform Squat and Smile test
timeFrame: Assessed at 6, 12, 26, and 52 week time point.
measure: Patient speed in completing walking speed test according to NIH 4 meter walking test
timeFrame: Assessed at 6, 12, 26, and 52 week time point.
Other outcomes:
Locations:
Study officials:
affiliation: University of California, San Francisco
name: Saam Morshed, MD, MPH
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: David Shearer, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Muhimbili Orthopaedic Institute
name: Billy Haonga, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Muhimbili Orthopaedic Institute
name: Edmund Eliezer, MD
role: PRINCIPAL_INVESTIGATOR
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