Allograft vs. Autograft Nonunion

Allograft vs. Autograft to Improve Timely Return to Duty Following Nonunion

The purpose of this research study is to find out if patients treated for nonunion fracture with autograft or allograft return to activity faster.

Study Overview

• Status: Not yet recruiting
• Conditions: Nonunion Fracture
• Intervention / Treatment: Procedure: Autograft; Procedure: Allograft

Detailed Description

The goal of this multi-center prospective randomized controlled trial is to compare short and long-term outcomes of adult patients with long-bone nonunion treated with autograft versus allograft. The main question it aims to answer is: will patients who receive an allograft return to work faster than patients who receive an autograft to treat nonunion fracture.

Participants will be randomized to one of two treatment groups and will complete follow-up surveys during their recovery.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christine Churchill; Phone Number: 704-355-6947; Email: Christine.Churchill@advocatehealth.org

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Atrium Health Carolinas Medical Center
      • Sub-Investigator: Rachel B Seymour, PhD
      • Sub-Investigator: Madhav Karunakar, MD
      • Sub-Investigator: Kevin Phelps, MD
      • Sub-Investigator: Laurence Kempton, MD
      • Sub-Investigator: Meghan Wally, PhD
      • Sub-Investigator: Suman Medda, MD
      • Sub-Investigator: Sarah Pierrie, MD
      • Contact: Rachel B Seymour, PhD; Phone Number: 704-441-5365; Email: Rachel.Seymour@advocatehealth.org
      • Contact: Christine Churchill, MA; Email: Christine.Churchill@advocatehealth.org
      • Sub-Investigator: Sophia Traven, MD
      • Sub-Investigator: Garrett Bullock, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients 18 years or older
• Long bone (tibia, femur, and humerus) nonunion appropriate for either study treatment: to be treated with bone graft harvested from a remote site or using reamer harvester (RIA)
• Nonunion surgery to be performed at least five months after initial fracture fixation
• Prior operative fixation of fracture
• Radiographic apparent bone gap (RABG) of >5cm

Exclusion Criteria:

• Patient that speaks neither English nor Spanish
• Patients whose treatment plan includes local autograft only (available callus from the nonunion site or no planned bone graft)
• Known active infection (defined as any clinical signs or symptoms of active infection, such as fevers, wound redness, warmth, swelling, induration or drainage, and abnormal while blood cell count, erythrocyte sedimentation rate, or C-reactive protein) being treated with antibiotics
• Body mass index greater than 50
• Patients unlikely to follow-up due to homelessness, or planning follow-up at another institution
• Prisoner

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Autograft; Patients randomized to autograft	Procedure: Autograft; Surgeons will decide on the location and method of donor site based on the clinical situation. Most commonly, bone graft will be harvested from the anterior or posterior iliac crest or utilizing the Reamer Irrigator Aspirator in an appropriate long bone. Surgeons may choose to harvest autograft from proximal tibia or distal femur. Donor site location is at the discretion of treating surgeon for patients who randomize to autograft. This treatment arm will not include local autograft only. For large bone defects requiring expansion of autograft with allograft, this will be allowed and recorded. We will use intent-to-treat for statistical analysis of those with allograft expansion of autograft. This autograft will be applied to the nonunion site using the surgeon's typical technique. Internal fixation, revision of fixation, and/or augmentation of fixation will be performed at the discretion of the surgeon.
Active Comparator: Allograft; Patients randomized to allograft.	Procedure: Allograft; Allograft bone will consist of cancellous or corticocancellous sterile packaged human cadaveric bone. No bone morphogenetic protein, bone marrow aspirate, or other biologic augment will be added. Demineralized bone matrix may be added at the surgeon's discretion. This allograft will be applied to the nonunion site using the surgeon's typical technique. Internal fixation, revision of fixation, and/or augmentation of fixation will be performed at the discretion of the surgeon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic Equivalent for Tasks Score	Time to return to work/duty will be measured using the the International Physical Activity Questionnaire (IPAQ).The IPAQ is a validated, self-report measure that captures detailed information about participation in a wide range of physical activities, including the number of days and amount of time spent in the previous 7 days. Responses for each type of physical activity are then transformed into the number of Metabolic Equivalent for Tasks (METs), and a METs/week is calculated for each patient.	Week 6
Metabolic Equivalent for Tasks Score	Time to return to work/duty will be measured using the the International Physical Activity Questionnaire (IPAQ).The IPAQ is a validated, self-report measure that captures detailed information about participation in a wide range of physical activities, including the number of days and amount of time spent in the previous 7 days. Responses for each type of physical activity are then transformed into the number of Metabolic Equivalent for Tasks (METs), and a METs/week is calculated for each patient.	Month 3
Metabolic Equivalent for Tasks Score	Time to return to work/duty will be measured using the the International Physical Activity Questionnaire (IPAQ).The IPAQ is a validated, self-report measure that captures detailed information about participation in a wide range of physical activities, including the number of days and amount of time spent in the previous 7 days. Responses for each type of physical activity are then transformed into the number of Metabolic Equivalent for Tasks (METs), and a METs/week is calculated for each patient.	Month 6
Metabolic Equivalent for Tasks Score	Time to return to work/duty will be measured using the the International Physical Activity Questionnaire (IPAQ).The IPAQ is a validated, self-report measure that captures detailed information about participation in a wide range of physical activities, including the number of days and amount of time spent in the previous 7 days. Responses for each type of physical activity are then transformed into the number of Metabolic Equivalent for Tasks (METs), and a METs/week is calculated for each patient.	Month 12
Average Time to Return to Work/Duty	Average number of days it takes for participants to return to work/duty	Week 6
Average Time to Return to Work/Duty	Average number of days it takes for participants to return to work/duty	Month 3
Average Time to Return to Work/Duty	Average number of days it takes for participants to return to work/duty	Month 6
Average Time to Return to Work/Duty	Average number of days it takes for participants to return to work/duty	Month 12
Number of Participants Returned to Work	Determined by asking whether subjects have returned to work	Week 6
Number of Participants Returned to Work	Determined by asking whether subjects have returned to work	Month 3
Number of Participants Returned to Work	Determined by asking whether subjects have returned to work	Month 6
Number of Participants Returned to Work	Determined by asking whether subjects have returned to work	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Union	Percentage of union will be assessed via radiographs and determined by the treating surgeon.	Week 6, Month 3, Month 6, Month 12
Time to Union	Number of days to union	Week 6, Month 3, Month 6, Month 12
Radiographic Union Scale in Tibial fractures (RUST) score	The RUST score ranges from a minimum score of 4 (definitely not healed) to a maximum score of 12 (completely healed). The final x-ray obtained within a 12-month period following injury will be uploaded to REDCap for review by a blinded panel of investigators from participating sites.	Month 12
Number of Participants who Return to the Operating Room	Number of participants who return to the Operating Room after procedure	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Physical Function	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means higher physical function.	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Anxiety	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of anxiety.	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Depression	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of depression	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Fatigue	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of fatigue.	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Sleep Disturbance	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of sleep disturbance.	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Pain Interference	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of pain interference.	Week 6, Month 3, Month 6, Month 12
PROMIS-29 Subscale - Ability to Participate in Social Roles and Activities	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher ability to participate in social roles and activities.	Week 6, Month 3, Month 6, Month 12
Number of Resource Utilizations	Healthcare utilization, including new hospitalizations, emergency department visits, clinic visits, imaging, and physical therapy sessions will be documented at all follow-up visits	Week 6, Month 3, Month 6, Month 12
Pain Intensity Scores	Pain will be assessed using the Brief Pain Inventory (BPI). The BPI is a commonly used and validated 15-item measure of pain intensity and interference with daily life. Worst pain score 1-4 = mild pain, 5-6 = moderate pain, 7-10 = severe pain.	Week 6, Month 3, Month 6, Month 12
Veterans RAND 12 Item Health Survey (VR-12) Scores	The VR-12 is a measure of global health that correspond to seven domains: general health, physical functioning, role limitations, pain, fatigue, social functioning, and mental health. Together, these items are summarized into a Physical Component Score and a Mental Component Score. Scores range from 0-100 with higher scores indicating better physical and mental health functioning.	Week 6, Month 3, Month 6, Month 12
Work Productivity and Activity Impairment Questionnaire Scores	Participants who report return to work/duty will complete the Work Productivity and Activity Impairment Questionnaire, a validated instrument that measures work time missed and work and activity impairment due to health problems. Measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. The higher number of day equates to more health problems.	Week 6, Month 3, Month 6, Month 12
Number of Complications	Number of major complications, including infection, implant failure, unplanned or planned return to the operating room related to the nonunion procedure, deep venous thrombosis, or pulmonary embolism.	Week 6, Month 3, Month 6, Month 12

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Joseph R Hsu, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Allograft; Autograft; Nonunion
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Ununited; Surgical Procedures, Operative; Transplantation; Transplantation, Autologous; Transplantation, Homologous
• Other Study ID Numbers: IRB00140521; HT9425-25-1-0424 (Other Grant/Funding Number: Department of Defense)

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