Intramedullary Nailing Versus External Fixation in Open Tibia Fractures in Tanzania

Not Applicable

Completed

• Conditions: Open Fracture of Tibia; Tibial Fractures; Trauma
• Interventions: Procedure: Intramedullary nailing with standard SIGN nail; Procedure: External Fixation with uniplanar Dispofix external fixator

• Registration Number: NCT03861624
• Lead Sponsor: University of California, San Francisco

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.

Study Timeline

• Study Start: 2015-12-17
• Primary Completion: 2017-03-25
• Study Completion: 2017-03-25
• Study First Submitted: 2019-02-25
• Study First Submitted QC: 2019-02-27
• Study First Posted: 2019-03-04
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-26
• Last Update Posted: 2022-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 240

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intramedullary nailing	Intramedullary nailing with standard SIGN nail	Patients receive definitive fixation of AO/OTA-42 open tibia diaphyseal fractures via Intramedullary nailing with standard SIGN nail.
External Fixation	External Fixation with uniplanar Dispofix external fixator	Patients receive definitive fixation of AO/OTA-42 open tibia diaphyseal fractures External Fixation with uniplanar Dispofix external fixator.

Primary Outcome Measures

Name	Time	Method
Rate of composite, all-cause reoperation	One year of definitive skeletal stabilization	The use of composite outcomes has been validated in a wide range of clinical trials. Primary events included in the composite outcome include: infection or hematoma, bone grafting, implant conversion or exchange \>6 weeks after index procedure, implant removal, dynamization of intramedullary nail, osteotomy, amputation.

Secondary Outcome Measures

Name	Time	Method
Rate of superficial infection	Assessed at clinical follow-up appointments at 2, 6, 12, 26, and 52 weeks	As defined by center for disease control (CDC) surveillance definitions, to include pin tract infections and cellulitis which resolves with use of antibiotics and local wound care.
Rate of deep infection	Assessed at clinical follow-up appointments at 2, 6, 12, 26, and 52 weeks	As defined by CDC surveillance definitions, to include deep abscess or osteomyelitis.
Number of participants with clinical nonunion	Assessed at clinical follow-up appointments at 6, 12, 26, and 52 weeks	Union of fracture healing will be assessed by absence of movement at fracture site and time to painless weight bearing. Non-union will be defined as fracture failure to heal beyond six months from date of injury.
Number of participants with radiographic nonunion	Assessed at clinical follow-up appointments at 6, 12, 26, and 52 weeks	Radiographic union will be assessed using rate of callous formation and visibility of fracture line as measured by the Radiographic union score for tibia (RUST) score
Number of participants with malunion	Assessed at clinical follow-up appointments at 6, 12, 26, and 52 weeks	Post-operative malalignment will be defined as leg length discrepancy (\>1 cm shortening), angular malalignment (\> 5 degrees sagittal or coronal angulation referenced contralateral leg radiographs, if non-injured), or malrotation (\>10 degrees, determined by Foot-Thigh Angle).
Number of participants with implant failure	Assessed at clinical follow-up appointments at 2, 6, 12, 26, and 52 weeks	Implant failure will be defined as breakage or loosening of any implant component at bone-implant interface which necessitates re-operation.
Health-related quality of life	Assessed at 2, 6, 12, 26, and 52 week time point.	Health related quality of life measured by Euro Quality of Life-5 Dimension (EuroQoL-5D, EQ5D) Index.; Contains 5 domains: Mobility, Self-Care, Usual activities, Pain/discomfort, Anxiety/depression Each domain contains 3 levels of health state pertaining to that level. Index score is calculated via weighted scores across each domain. Measured from 0 to 1 where 0 is equivalent to death and 1 is equivalent to perfect state of health.
Visual analogue pain score	Assessed at 2, 6, 12, 26, and 52 week time point.	Visual analogue pain score represents a patient's current level of pain scored from 1-10 where 1 = no/minimal pain to 10 = worst possible pain.
Participant knee range of motion	Assessed at 6, 12, 26, and 52 week time point.	Includes: * Maximum knee extension/flexion as measured with a goniometer; * Values are recorded in degrees from neutral/hyperextension to ≥ 30 by intervals of 5 degrees for maximum knee extension; * Values are recorded in degrees from ≤30 degrees to ≥140 degrees by intervals of 10 degrees for maximum knee flexion
Participant ankle range of motion	Assessed at 6, 12, 26, and 52 week time point.	Includes: * Maximum ankle dorsiflexion/plantarflexion as measured with a goniometer; * Values are recorded in degrees from -15 degrees to \>25 degrees by intervals of 5 degrees for maximum ankle dorsiflexion; * Values are recorded in degrees from \<10 degrees to \>50 degrees by intervals of 10 degrees for maximum ankle plantarflexion
Participant ability to perform Squat and Smile test	Assessed at 6, 12, 26, and 52 week time point.	The Squat and Smile test (S\&S) is a functional assessment of squatting ability used by SIGN Fracture Care International to quickly assess fracture healing.; Squat depth is categorized by squat level: unable (1), above knee level (2), at knee level (3) or below knee level (4); -Values are scored from 1 to 4 where 1 is worst and 4 is best.; Support component is categorized by: requiring both hands for support with squatting (1), one hand for support with squatting (2), or no hands for support with squatting (3) -Values are scored from 1 to 3 where 1 is worst and 3 is best; Smile component is categorized into painful grimace (1), neutral expression (2), and smile (3) where painful grimace is worst and smile is best.; -Values are scored from 1 to 3 where 1 is worst and 3 is best; Each component is scored and evaluated individually as separate domains. There is no pooling of scores.
Patient speed in completing walking speed test according to NIH 4 meter walking test	Assessed at 6, 12, 26, and 52 week time point.	Measures locomotion; Participants walk 4 meters at their usual pace and complete one practice and two timed trials. Raw scores are recorded at the time in seconds required to walk four meters on each of the two trials with the better trial used as the final score.