Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trialBMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i5351 (Published 25 October 2016) Cite this as: BMJ 2016;355:i5351
- TRUST Investigators writing group,
- Jason W Busse, associate professor1 2 3,
- Mohit Bhandari, professor1 4,
- Thomas A Einhorn, professor5,
- Emil Schemitsch, professor6,
- James D Heckman, clinical professor7,
- Paul Tornetta III, professor5,
- Kwok-Sui Leung, professor8,
- Diane Heels-Ansdell, clinical epidemiologist1,
- Sun Makosso-Kallyth, clinical epidemiologist2,
- Gregory J Della Rocca, associate professor9,
- Clifford B Jones, clinical professor10,
- Gordon H Guyatt, distinguished professor1 11
- 1Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, L8S 4K1, Canada
- 2Department of Anesthesia, McMaster University, Hamilton, ON L8S 4K1, Canada
- 3Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON L8S 4K1, Canada
- 4Department of Surgery, McMaster University, Hamilton, ON L8S 4L8, Canada
- 5Department of Orthopedic Surgery, NYU Langone Medical Center, New York, NY 10016, USA
- 6Department of Surgery, University of Western Ontario, London, ON N6A 4V2, Canada
- 7Department of Orthopedic Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03766, USA
- 8Department of Orthopedics and Traumatology, Chinese University of Hong Kong, Shatin, Hong Kong, China
- 9Department of Orthopedic Surgery, University of Missouri, Columbia, MO 65212, USA
- 10Center for Orthopedic Research and Education, CORE, Banner University, Phoenix, AZ, 85023, USA
- 11Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
- Correspondence to: J W Busse, 1200 Main Street West, HSC-2U1, Department of Anesthesia, McMaster University, Hamilton, ON, L8S 4K1, Canada
Objective To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures.
Design A concealed, randomized, blinded, sham controlled clinical trial with a parallel group design of 501 patients, enrolled between October 2008 and September 2012, and followed for one year.
Setting 43 North American academic trauma centers.
Participants Skeletally mature men or women with an open or closed tibial fracture amenable to intramedullary nail fixation. Exclusions comprised pilon fractures, tibial shaft fractures that extended into the joint and required reduction, pathological fractures, bilateral tibial fractures, segmental fractures, spiral fractures >7.5 cm in length, concomitant injuries that were likely to impair function for at least as long as the patient’s tibial fracture, and tibial fractures that showed <25% cortical contact and >1 cm gap after surgical fixation. 3105 consecutive patients who underwent intramedullary nailing for tibial fracture were assessed, 599 were eligible and 501 provided informed consent and were enrolled.
Interventions Patients were allocated centrally to self administer daily LIPUS (n=250) or use a sham device (n=251) until their tibial fracture showed radiographic healing or until one year after intramedullary fixation.
Main outcome measures Primary registry specified outcome was time to radiographic healing within one year of fixation; secondary outcome was rate of non-union. Additional protocol specified outcomes included short form-36 (SF-36) physical component summary (PCS) scores, return to work, return to household activities, return to ≥80% of function before injury, return to leisure activities, time to full weight bearing, scores on the health utilities index (mark 3), and adverse events related to the device.
Results SF-36 PCS data were acquired from 481/501 (96%) patients, for whom we had 2303/2886 (80%) observations, and radiographic healing data were acquired from 482/501 (96%) patients, of whom 82 were censored. Results showed no impact on SF-36 PCS scores between LIPUS and control groups (mean difference 0.55, 95% confidence interval −0.75 to 1.84; P=0.41) or for the interaction between time and treatment (P=0.30); minimal important difference is 3-5 points) or in other functional measures. There was also no difference in time to radiographic healing (hazard ratio 1.07, 95% confidence interval 0.86 to 1.34; P=0.55). There were no differences in safety outcomes between treatment groups. Patient compliance was moderate; 73% of patients administered ≥50% of all recommended treatments.
Conclusions Postoperative use of LIPUS after tibial fracture fixation does not accelerate radiographic healing and fails to improve functional recovery.
Study registration ClinicalTrialGov Identifier: NCT00667849
Contributors: JWB (chair of writing group), MB (associate chair), TAE, ES, JDH, PT III, K-SL, and GHG conceived and designed the study. JWB, MB, and GHG acquired the funding. Data collection was monitored by Alquest (contract research organization). JWB, DH-A, SM-K, and GHG developed the statistical analysis plan, conducted the analysis and interpreted the data. JWB, DH-A, and SM-K had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. JWB drafted the manuscript, which was revised by the other authors (MB, TAE, ES, JDH, PT III, K-SL, GHG, GJDR and CBJ). All authors read and approved the final manuscript. JWB is guarantor.
Funding: This study was an investigator-initiated trial, supported by grants from the Canadian Institutes of Health Research (CIHR) (MCT 67815, Co-PIs: GH Guyatt, M Bhandari), and an industry grant from Smith & Nephew. The CIHR had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Smith & Nephew personnel reviewed initial drafts of the trial protocol and raised many issues about alternative approaches to study design. Issues regarding the protocol were resolved through negotiation between Smith & Nephew and the trial steering committee. Final decisions regarding the protocol and issues that arose during the conduct of the trial were the purview of the trial steering committee. The investigators had full access to all trial data. Smith & Nephew had no role the initial preparation of the current study manuscript but had the right to review the manuscript and make non-binding comments and suggestions.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: TAE, ES, and MB have received consulting fees from Smith & Nephew, the manufacturer of the study device. PT receives royalties from Smith & Nephew. GJDR is a paid consultant for Bioventus LLC, which is 51% owned by Essex Woodlands and 49% by Smith & Nephew. MB is supported, in part, by a Canada research chair, McMaster University.
Ethical approval: The study protocol was approved by McMaster University research ethics board (REB#08-171) and local boards at each participating site.
Data sharing: Full dataset and statistical code is available from the corresponding author. Patient consent was not obtained for data sharing, but the data are anonymized and risk of identification is low.
Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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