Effort helping to define standards for tibial fracture care
As a third-year orthopaedic surgical resident, Mohit Bhandari, MD, was asked what he would like to accomplish in the next decade. “I would like to contribute something meaningful to the orthopaedic community beyond my surgical practice,” he responded.
Although he had virtually no funding when the project began, Dr. Bhandari was able to recruit a distinguished steering committee whose members include Gordon Guyett, MD; Marc F. Swiontkowski, MD; Paul Tornetta III, MD; David Sanders, MD; Stephen Walter, PhD; and Emil H. Schemitsch, MD.
The collaborative study eventually involved more than 200 orthopaedic surgeons and 40 research coordinators in 29 centers and three countries. It was given the acronym SPRINT—Study to Prospectively Evaluate Reamed Intramedullary (IM) Nails in Tibial Fractures.
Seeking the best evidence
Dr. Bhandari and his co-investigators began by conducting a primary meta-analysis to identify the best evidence to manage open fractures of the tibial shaft.
“The findings were quite conclusive regarding the advantage of IM nailing in the management of open tibial fractures,” Dr. Bhandari stated. “The key question of the relative efficacy of reamed versus unreamed, however, remained largely inconclusive.”
A second meta-analysis to help answer the question on the relative efficacy of reamed and unreamed IM nailing in closed tibial shaft fractures was also inconclusive.
“Our meta-analyses provided a strong rationale for a large, definitive randomized trial comparing reamed and unreamed nail insertion in both closed and open fractures,” Dr. Bhandari said.
“To gauge global interest in such a trial and gain a precise estimate of the degree of discordance in clinical practice, large scale surveys of the global orthopaedic community were needed,” he continued.
Surveying the world
The researchers surveyed 577 surgeons in the United States, Canada, Europe, Africa, Asia, and South America, and received a 77 percent response rate.
Most surgeons preferred using IM nails to treat open tibial shaft fractures, closed low energy fractures, closed high energy fractures, and closed fractures with associated compartment syndrome (Table 1). Use of IM nails declined as the severity of the soft-tissue injury increased.
“Surgeons varied in their preference for unreamed or reamed nails for both closed and open fractures,” said Dr. Bhandari.
Re-operation as the primary outcome
Although infection and nonunion are commonly used as patient outcomes, Dr. Bhandari’s team chose re-operation as the primary outcome.
Both postsurgical infection and nonunion frequently led to second surgeries. “Because of the risks and costs to the patient, and the costs to the health system, re-operation represents an important outcome from both individual and societal points of view,” stated Dr. Bhandari.
After identifying factors that would predict re-operations, the researchers conducted a retrospective observational study to determine which predictive factors were associated with an increased risk of re-operation. They identified the following factors:
- presence of a transverse fracture
- presence of a fracture gap, defined as lack of cortical contact between fracture ends following fixation
- presence of any size open fracture wound
According to Dr. Bhandari, few reports considered fracture gap or the degree of cortical continuity as risk factors for re-operation. But they were critical for the protocol development for the SPRINT trial.
“Individuals responsible for assessing fracture healing in large-scale trials must have an accurate, cost-effective method for conducting the assessment,” he said.
Another study determined the practicality of using radiographs to assess fracture healing by measuring inter-observer (between orthopaedic surgeons) and intra-observer reliability. “To assess reliability we used scores on the degree of union, number of cortices bridged, extent of bony callus development, and the overall healing rating,” explained Dr. Bhandari.
Cortical continuity received the most consistent score for reliability of radiographic healing. “The use of cortical continuity to assess radiographic healing is particularly apt for IM fractures, because the nail allows only the cortical detail to be assessed accurately.
“This finding, along with the results of the predictive prognostic factors, indicated the importance of cortical continuity as a critical indicator of fracture healing to be used in assessing our composite primary outcome—re-operation,” he stated.
Setting the stage for a successful trial
A pilot trial helped researchers understand why patients dropped out of randomized controlled trials and enabled researchers to design strategies to increase patient retention. It also underscored the need for a 6-month proscription of re-operation to prevent possible bias, blinded adjudication for outcomes, and a concealed central randomization process. A central adjudication committee was established to review all radiographs and all other relevant data.
The SPRINT Trial included 29 centers in Canada, the United States, and the Netherlands and enrolled 1,319 adult patients with open (Gustilo Types I-IIIB) or closed fractures (Tscherne Types 0-3) of the tibial shaft. Patients agreed to surgical treatment with an IM nail and to randomization into either reamed or unreamed nail groups. The trial started in July 2000 and was completed in January 2007.
Of the 1,319 patients that enrolled in the trial, 1,206 participants (93 percent) completed the final follow-up visit at 1 year. Re-operation rates were dramatically lower than previous studies. Only 4.6 percent of patients required implant exchange or bone graft for nonunion compared to an average of 12.4 percent in five previous randomized trials.
The investigators reported the following three important findings:
- By allowing at least 6 months for fracture healing, surgeons may reduce the number of re-operations for nonunions.
- The increased number of dynamizations present with unreamed IM nails supports the use of reamed IM nailing in closed tibial shaft fractures.
- Unreamed nail insertion may reduce re-operation risk but this conclusion requires further confirmation and study.
“Reamed or unreamed nailing is important but simply waiting may be even more important in reducing overall re-operation rates. Most fractures will heal if left alone after treatment. We recommend waiting as long as you possibly can, with 6 months as a minimum. That single protocol difference resulted in a significantly lower re-operation rate,” Dr. Bhandari said.
“SPRINT proves that multinational trials can work, bringing surgeons from around the world together for a common goal,” he said. “It set new benchmarks for trial infrastructure, quality assurance, and outcomes assessment that have changed the paradigm for clinical trial design in orthopaedic surgery.”
Dr. Bhandari reports the following disclosures—Amgen Co., Pfizer, Baxter, King Pharmaceuticals, Wyeth, Smith & Nephew, Stryker, Canadian Institutes of Health Research (CIHR), Canadian Orthopedic Foundation, AO, DePuy, A Johnson & Johnson Company, National Institutes of Health (NIAMS & NICHD).
This study was funded by Research Grants from the Canadian Institutes of Health Research #MCT-38140 [PI: G. Guyatt], National Institutes of Health NIAMS-072; R01 AR48529 [PI: M.Swiontkowski], Orthopaedic Research and Education Foundation [American Academy of Orthopaedic Surgeons [PI: P. Tornetta III], Orthopaedic Trauma Association [PI: M. Bhandari]. Smaller site specific grants were also obtained from Hamilton Health Sciences Research Grant [PI: M. Bhandari] and Zimmer [PI: M. Bhandari]. Dr. Bhandari is funded, in part, by a Canada Research Chair in Musculoskeletal Trauma, McMaster University.
Dr. Bhandari will present his award-winning paper on Tuesday, March 9, in Auditorium A of the Morial Convention Center, as part of the Orthopaedic Research Society Annual Meeting; the OREF Clinical Research Award will be presented to the authors during the Opening Ceremonies of the AAOS Annual Meeting, on Wednesday, March 10, in the La Nouvelle Ballroom, Morial Convention Center.
Annie Hayashi is a contributing writer for AAOS Now. She can be reached at firstname.lastname@example.org
- Let the fracture heal for at least 6 months before considering re-operation.
- Most physicians prefer using reamed IM nailing in closed tibial shaft fractures.