A Study Protocol for a Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin Versus Saline in Open Tibia Fractures (pGO-Tibia) in Dar Es Salaam, Tanzania

Overview

Journal Pilot Feasibility Stud

Publisher Biomed Central

Date 2021 Feb 11

PMID 33568230

Citations 7

Authors

Ericka P von Kaeppler

Claire Donnelley

Syed H Ali

Heather J Roberts

John M Ibrahim

Hao-Hua Wu

Edmund N Eliezer

Travis C Porco

Billy T Haonga

Saam Morshed

David W Shearer

Affiliations

Soon will be listed here.

Abstract

Background: Open tibia fractures are a major source of disability in low- and middle-income countries (LMICs) due to the high incidence of complications, particularly infection and chronic osteomyelitis. One proposed adjunctive measure to reduce infection is prophylactic local antibiotic delivery, which can achieve much higher concentrations at the surgical site than can safely be achieved with systemic administration. Animal studies and retrospective clinical studies support the use of gentamicin for this purpose, but no high-quality clinical trials have been conducted to date in high- or low-income settings.

Methods: We describe a protocol for a pilot study conducted in Dar es Salaam, Tanzania, to assess the feasibility of a single-center masked randomized controlled trial to compare the efficacy of locally applied gentamicin to placebo for the prevention of fracture-related infection in open tibial shaft fractures.

Discussion: The results of this study will inform the design and feasibility of a definitive trial to address the use of local gentamicin in open tibial fractures. If proven effective, local gentamicin would be a low-cost strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries.

Trial Registration: ClinicalTrials.gov, Registration # NCT03559400 ; Registered June 18, 2018.

Citing Articles

Orthopaedic and trauma research in Tanzania: A scoping review.

Blackman B, Barnett S, Premkumar A, Sheth N PLoS One. 2024; 19(6):e0304218.

PMID: 38837974 PMC: 11152290. DOI: 10.1371/journal.pone.0304218.

Estimating the economic impact of complications after open tibial fracture: A secondary analysis of the pilot Gentamicin Open Tibia trial (pGO-Tibia).

Flores M, Brown K, Haonga B, Morshed S, Shearer D OTA Int. 2024; 7(1):e290.

PMID: 38249318 PMC: 10798688. DOI: 10.1097/OI9.0000000000000290.

Best Practices for Developing International Academic Partnerships in Orthopaedics.

Brown K, Flores M, Haonga B, Chokotho L, OMarr J, Rodarte P J Bone Joint Surg Am. 2023; 106(10):924-930.

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A pilot, masked, randomized controlled trial to evaluate local gentamicin versus saline in open tibial fractures (pGO-Tibia).

Haonga B, Ngunyale P, von Kaeppler E, Donnelley C, Won N, Eliezer E OTA Int. 2023; 6(2):e268.

PMID: 37719315 PMC: 10503693. DOI: 10.1097/OI9.0000000000000268.

GO-Tibia: a masked, randomized control trial evaluating gentamicin versus saline in open tibia fractures.

Haonga B, OMarr J, Ngunyale P, Ngahyoma J, Kessey J, Sasillo I Trials. 2023; 24(1):406.

PMID: 37322521 PMC: 10268448. DOI: 10.1186/s13063-023-07410-0.

References

Litrenta J, Tornetta 3rd P, Mehta S, Jones C, OToole R, Bhandari M . Determination of Radiographic Healing: An Assessment of Consistency Using RUST and Modified RUST in Metadiaphyseal Fractures. J Orthop Trauma. 2015; 29(11):516-20. DOI: 10.1097/BOT.0000000000000390. View

Barei D, Nork S, Mills W, Henley M, Benirschke S . Complications associated with internal fixation of high-energy bicondylar tibial plateau fractures utilizing a two-incision technique. J Orthop Trauma. 2004; 18(10):649-57. DOI: 10.1097/00005131-200411000-00001. View

Edson R, Terrell C . The aminoglycosides. Mayo Clin Proc. 1999; 74(5):519-28. DOI: 10.4065/74.5.519. View

Cavanaugh D, Berry J, Yarboro S, Dahners L . Better prophylaxis against surgical site infection with local as well as systemic antibiotics. An in vivo study. J Bone Joint Surg Am. 2009; 91(8):1907-12. PMC: 2714810. DOI: 10.2106/JBJS.G.01237. View

Selby N, Shaw S, Woodier N, Fluck R, Kolhe N . Gentamicin-associated acute kidney injury. QJM. 2009; 102(12):873-80. DOI: 10.1093/qjmed/hcp143. View

Peng J, Ren Y, He W, Li Z, Yang J, Liu Y . Epidemiological, Clinical and Microbiological Characteristics of Patients with Post-Traumatic Osteomyelitis of Limb Fractures in Southwest China: A Hospital-Based Study. J Bone Jt Infect. 2017; 2(3):149-153. PMC: 5441147. DOI: 10.7150/jbji.20002. View

. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392(10159):1789-1858. PMC: 6227754. DOI: 10.1016/S0140-6736(18)32279-7. View

Harris A, Althausen P, Kellam J, Bosse M, Castillo R . Complications following limb-threatening lower extremity trauma. J Orthop Trauma. 2008; 23(1):1-6. DOI: 10.1097/BOT.0b013e31818e43dd. View

OToole R, Joshi M, Carlini A, Murray C, Allen L, Scharfstein D . Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter, Randomized, Controlled Trial (VANCO Study). J Orthop Trauma. 2017; 31 Suppl 1:S18-S24. DOI: 10.1097/BOT.0000000000000801. View

10.

Reilly M, Zbrozek A, Dukes E . The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993; 4(5):353-65. DOI: 10.2165/00019053-199304050-00006. View

11.

Chan A, Tetzlaff J, Altman D, Laupacis A, Gotzsche P, Krleza-Jeric K . SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013; 158(3):200-7. PMC: 5114123. DOI: 10.7326/0003-4819-158-3-201302050-00583. View

12.

Teare M, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters S . Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014; 15:264. PMC: 4227298. DOI: 10.1186/1745-6215-15-264. View

13.

Harris P, Taylor R, Thielke R, Payne J, Gonzalez N, Conde J . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2008; 42(2):377-81. PMC: 2700030. DOI: 10.1016/j.jbi.2008.08.010. View

14.

Bhandari M, Guyatt G, Tornetta 3rd P, Schemitsch E, Swiontkowski M, Sanders D . Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg Am. 2008; 90(12):2567-78. PMC: 2663330. DOI: 10.2106/JBJS.G.01694. View

15.

Morgenstern M, Vallejo A, McNally M, Moriarty T, Ferguson J, Nijs S . The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. Bone Joint Res. 2018; 7(7):447-456. PMC: 6076360. DOI: 10.1302/2046-3758.77.BJR-2018-0043.R1. View

16.

Westgeest J, Weber D, Dulai S, Bergman J, Buckley R, Beaupre L . Factors Associated With Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects. J Orthop Trauma. 2015; 30(3):149-55. DOI: 10.1097/BOT.0000000000000488. View

17.

Fassbender M, Minkwitz S, Kronbach Z, Strobel C, Kadow-Romacker A, Schmidmaier G . Local gentamicin application does not interfere with bone healing in a rat model. Bone. 2013; 55(2):298-304. DOI: 10.1016/j.bone.2013.04.018. View

18.

Miclau T, Edin M, Lester G, Lindsey R, Dahners L . Bone toxicity of locally applied aminoglycosides. J Orthop Trauma. 1995; 9(5):401-6. DOI: 10.1097/00005131-199505000-00007. View

19.

Carver D, Kuehn S, Weinlein J . Role of Systemic and Local Antibiotics in the Treatment of Open Fractures. Orthop Clin North Am. 2017; 48(2):137-153. DOI: 10.1016/j.ocl.2016.12.005. View

20.

Henry S, Galloway K . Local antibacterial therapy for the management of orthopaedic infections. Pharmacokinetic considerations. Clin Pharmacokinet. 1995; 29(1):36-45. DOI: 10.2165/00003088-199529010-00005. View