Intramedullary Bone Grafting for Open Tibial Shaft Fractures

Open Tibial Shaft Fractures: Can Packing the Exposed Cortex With Intramedullary Reamings Increase Union Rates

This study will examine if there is a difference between the time to full union between the control group and the study group. Each group will be composed of patients who have an open fracture in the mid tibia. Both groups will undergo primary fixation via reamed intramedulary nailing (IMN), a common treatment for tibia shaft fractures in adults. The study group will have a bone graft applied to the open cortex of the fracture. The bone graft will be composed of the intramedullary reamings, which are a byproduct produced when the intramedullary canal is reamed in preparation for insertion of the IMN.

Study Overview

• Status: Recruiting
• Conditions: Tibial Fractures; Nonunion of Fracture; Delayed Union of Fracture
• Intervention / Treatment: Procedure: Intramedullary Bone Graft

Detailed Description

Open fractures of the tibial diaphysis are known to have high rates of nonunion or delayed union, with widely varying nonunion rates reported to be between 15% and 60% even in lower Gustilo Anderson grade (types I, II, and IIIA) open fractures. Nonunions are costly as they require more healthcare services and result in increased patient pain and disability. A previous study has demonstrated that the use of bone morphogenic protein (BMP) at the time of definitive tibial shaft fracture fixation significantly reduced the risk of delayed union. However, BMP is costly and is rarely used for this purpose. Intramedullary bone graft (IMBG) collected by the reamer-irrigator-aspirator (RIA) technique has been shown to be effective for producing bone graft to stimulate healing and treat larger defects in long bones as well as in the treatment of nonunions. However, the RIA apparatus also introduces and extra expense to the operation and produces more bone graft than would be needed for packing of the open cortex in non-segmental fractures without bone loss. The investigator's study aims to determine if packing the exposed fracture cortex with a small volume of IMBG collected from the tip of a standard reamer during intramedullary nailing can effectively reduce rate of delayed union and nonunion in open tibia shaft fractures.

This will be a prospective interventional study with two randomized, parallel groups. Patients with an open diaphyseal tibial fracture will be considered for study inclusion. Patients who consent to participate in the study will be randomized to one of two groups. The first will be the control group. This group will receive the standard of care for their injury, which consists of irrigation and debridement of the open fracture, reamed intramedullary nailing and primary wound closure. The second group, the intervention group, will also undergo irrigation and debridement of the open fracture with reamed intramedullary nailing, but will also receive a bone graft on the exposed cortex of the tibial fracture before primarily closing the wound. The bone graft will be made up of the product of the intramedullary reaming prior to the insertion of the intramedullary nail. This bone graft will be collected by wiping the reamings from the reamer tip into a sterile, pre-weighed container after each pass of the reamer through the medullary canal. Prior to introducing the graft into the exposed cortex, the graft will be weighed so that a record may be kept of the amount of graft collected and subsequently used in the procedure.

Each group will then receive identical follow-up care with clinic visits at 2, 8, 16, and 24 weeks post operatively, and will receive X-rays at the 8, 16, and 24 week visits. Each radiograph will be evaluated and assigned a Radiographic Union Scale in Tibial fractures (RUST) score by an independent evaluator. Additionally, the Lower Extremity Functional Scale (LEFS) questionnaire will be administered at enrollment, 8, 16, and 24 week visit to objectively measure patient progress in functional outcomes. The primary outcome measurement will be the rate of union of the fracture in both groups at 3 and 6 month follow up. Radiographic union of the fracture will be defined as the presence of cortical bridging on at least 3 of the 4 cortices or RUST score >10. Delayed union will be defined as failure to achieve cortical bridging on 3 of 4 cortices or a RUST score >10 by 6 months. Nonunion will be defined as a fracture that in the opinion of the treating surgeon has no possibility of healing without further intervention.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rodolfo Zamora, MD; Phone Number: 502-629-5460; Email: razamo02@louisville.edu
• Study Contact Backup: Name: Salwa M Rashid, MD, MPH; Phone Number: 5028526964; Email: sfrash01@louisville.edu

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Hospital
      • Contact: Rodolfo Zamora, MD; Phone Number: 502-629-5460; Email: razamo02@louisville.edu
      • Contact: Lauren M Nelson, MD; Phone Number: 831-535-3397; Email: lmgerm01@louisville.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient age 18 or older
• Patient with a Gustillo I, II, or IIIa open tibia shaft fracture to be treated primarily with an intramedullary nail
• Primary closure of the open fracture wound during the initial operation
• Consent to participate in the study.
• Are able and willing to return to the hospital or clinic for follow-up for a period of 6-9 months or until radiographic union.

Exclusion Criteria:

• Patients under the age of 18.
• Patients who are pregnant
• Patients with segmental tibia fractures or those with loss of bone
• Patients with skin defects over the tibia that cannot be closed primarily
• Patients with a pathologic fracture of the tibia
• Patient has quadriplegia or paraplegia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Patients in this group will undergo standard treatment for their open tibia shaft fracture (irrigation and debridement of their open fracture and reamed intramedullary nailing)
Experimental: Intervention; Patients in this group will receive a bone graft in addition to the undergoing standard treatment for their open tibia shaft fracture (irrigation and debridement of their open fracture and reamed intramedullary nailing)	Procedure: Intramedullary Bone Graft; Patients in this group will undergo standard treatment for their open tibia shaft fracture (irrigation and debridement of their open fracture and reamed intramedullary nailing), but will also have the reamings from the medullary canal preparation collected and packed into the exposed fracture cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Union at 6 months	Percentage of patients with the presence of cortical bridging on at least 3 of the 4 fracture cortices at 6 months	6 months
Radiographic Union at 4 months	Percentage of patients with the presence of cortical bridging on at least 3 of the 4 fracture cortices at 4 months	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower Extremity Functional Scale Score at 6 months	The Lower Extremity Functional Scale Score is a patient reported outcome measure that can be used clinically to measure initial function, ongoing progress, and outcomes in patients with impairment of the lower extremities due to musculoskeletal conditions or disorders. The test assesses activities of daily living, balance, coordination, functional mobility, occupational performance, quality of life, range of motion, and strength, and is scored out of 80 points. The minimum possible score is 0 and the maximum possible score is 80, with a higher score associated with better outcomes. The minimum clinically important difference for this scale is 9 points.	6 months
Lower Extremity Functional Scale Score at 4 months	The Lower Extremity Functional Scale Score is a patient reported outcome measure that can be used clinically to measure initial function, ongoing progress, and outcomes in patients with impairment of the lower extremities due to musculoskeletal conditions or disorders. The test assesses activities of daily living, balance, coordination, functional mobility, occupational performance, quality of life, range of motion, and strength, and is scored out of 80 points. The minimum possible score is 0 and the maximum possible score is 80, with a higher score associated with better outcomes. The minimum clinically important difference for this scale is 9 points.	4 months
Lower Extremity Functional Scale Score at 2 months	The Lower Extremity Functional Scale Score is a patient reported outcome measure that can be used clinically to measure initial function, ongoing progress, and outcomes in patients with impairment of the lower extremities due to musculoskeletal conditions or disorders. The test assesses activities of daily living, balance, coordination, functional mobility, occupational performance, quality of life, range of motion, and strength, and is scored out of 80 points. The minimum possible score is 0 and the maximum possible score is 80, with a higher score associated with better outcomes. The minimum clinically important difference for this scale is 9 points.	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return to work status at 6 months post injury	Percentage of patients who had returned to work at 6 months post injury	6 months
Return to work status at 4 months post injury	Percentage of patients who had returned to work at 4 months post injury	4 months
Return to work status at 2 months post injury	Percentage of patients who had returned to work at 2 months post injury	2 months

Collaborators and Investigators

• Sponsor: University of Louisville
• Investigators: Principal Investigator: Rodolfo Zamora, MD, University of Louisville

Publications and helpful links

General Publications

• Antonova E, Le TK, Burge R, Mershon J. Tibia shaft fractures: costly burden of nonunions. BMC Musculoskelet Disord. 2013 Jan 26;14:42. doi: 10.1186/1471-2474-14-42.
• O'Halloran K, Coale M, Costales T, Zerhusen T Jr, Castillo RC, Nascone JW, O'Toole RV. Will My Tibial Fracture Heal? Predicting Nonunion at the Time of Definitive Fixation Based on Commonly Available Variables. Clin Orthop Relat Res. 2016 Jun;474(6):1385-95. doi: 10.1007/s11999-016-4821-4.
• Riemer BL, DiChristina DG, Cooper A, Sagiv S, Butterfield SL, Burke CJ 3rd, Lucke JF, Schlosser JD. Nonreamed nailing of tibial diaphyseal fractures in blunt polytrauma patients. J Orthop Trauma. 1995 Feb;9(1):66-75. doi: 10.1097/00005131-199502000-00011.
• Sanders R, Jersinovich I, Anglen J, DiPasquale T, Herscovici D Jr. The treatment of open tibial shaft fractures using an interlocked intramedullary nail without reaming. J Orthop Trauma. 1994 Dec;8(6):504-10.
• Caudle RJ, Stern PJ. Severe open fractures of the tibia. J Bone Joint Surg Am. 1987 Jul;69(6):801-7.
• Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P, Choong P, Cinats J, Courtenay B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P, Holt M, Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P, Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T; BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002 Dec;84(12):2123-34. doi: 10.2106/00004623-200212000-00001.
• Dawson J, Kiner D, Gardner W 2nd, Swafford R, Nowotarski PJ. The reamer-irrigator-aspirator as a device for harvesting bone graft compared with iliac crest bone graft: union rates and complications. J Orthop Trauma. 2014 Oct;28(10):584-90. doi: 10.1097/BOT.0000000000000086.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2020
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): December 14, 2021
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Nonunion; Tibial diaphyseal fracture; Delayed union
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Fractures, Bone; Tibial Fractures; Fractures, Ununited
• Other Study ID Numbers: IRB Number: 18.1329

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No