Platelet-rich Plasma Combined With Conventional Surgery in the Treatment of Atrophic Nonunion of Femoral Shaft Fractures

Platelet-rich Plasma Combined With Conventional Surgery in the Treatment of Atrophic Nonunion of Femoral Shaft Fractures: a Prospective, Randomized, Controlled Clinical Trial

To objectively analyze the effectiveness of platelet-rich plasma (PRP) combined with conventional surgery in the treatment of atrophic nonunion of femoral shaft fractures.

Study Overview

• Status: Unknown
• Conditions: Nonunion of Fracture
• Intervention / Treatment: Procedure: conventional surgery; Procedure: autologous platelet-rich plasma

Detailed Description

History and current related studies:

Fracture healing is a continuous process, and if any phase is disturbed by unfavorable factors, the healing process will be blocked. Clinical studies have found that non-healing rate of long bone fracture was approximately 5%. A certain site and type of fracture, if not healed within a mean time (usually 3-6 months), is called delayed union by US Food and Drug Administration. Simultaneously, the fracture that has not healed after 9 months and has no tendency for further healing in the next 3 months is called nonunion. According to fracture end activity, nonunion is classified into hypertrophic nonunion and atrophic nonunion.7, 8 Hypertrophic nonunion is mostly caused by unstable fixation of fracture ends, and can be cured by strengthening the stability of fracture site using conventional surgery. Atrophic nonunion is difficult to be cured, because of the lack of adequate blood supply and bone formation at the fracture ends, so it is unable to form the periosteal callus. At present, atrophic nonunion is commonly treated by internal and external fixation combined with autologous bone graft, but this method has a long treatment cycle, and there is a situation that cannot be cured.

Platelet-rich plasma (PRP) is blood plasma that has been enriched with platelets by centrifuging autologous blood. Platelet after activation can secrete platelet derived growth factor, transforming growth factor beta, vascular endothelial growth factor and epidermal growth factor. These growth factors can promote cell proliferation and differentiation, matrix synthesis and vascular regeneration, and accelerate tissue healing and bone repair. PRP contains a large number of leukocytes, which can locally phagocytize bacteria, scavenge necrotic tissue, inhibit inflammatory reaction, and resist infection. PRP fibrin can locally build the three-dimensional structure required for tissue repair. Since Assoian et al. first isolated PRP and used PRP in the clinic in 1984, PRP has received increasing attention in areas such as oral and maxillofacial surgery, orthopedics, plastic surgery, and neurosurgery.

Data management:

Clinical researchers filled in the clinical trial observation form to ensure the data were accurate, complete and timely collected. After the trial, all data were input into the computer. After data collection, the main clinical investigators and inspectors monitored and checked the integrity and accuracy of the data. The data were locked by the main investigators. Data processing statisticians further verified and checked the completeness and accuracy of the data after data entry. Anonymized trial data will be published at www.figshare.com.

Statistical analysis:

1. Measurement data were expressed as the mean ± SD and analyzed using SPSS 17.0 software (SPSS, Chicago, IL, USA). Count data were expressed as a percentage.
2. A normality test and variance homogeneity test were conducted. Normally distributed data with homogeneity were compared using one-way analysis of variance. Non-normally distributed data were compared using Wilcoxon's two-sample rank sum test.
3. The incidence of adverse reactions between groups was compared using chi-square test. A P value of < 0.05 was considered statistically significant. Results followed the intention-to-treat principle.

Confidentiality:

Clinical trial observation forms and informed consents were password-protected. No person, other than an authorized researcher, might be in contact with it.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Femoral shaft fractures
• Fracture time is more than 9 months
• X-ray reveals gap and sclerosis at the fracture ends, medullary closure, osteoporosis, with the absence of trabecular bone formation among callus, and for more than 3 months
• Magnetic resonance imaging reveals widened gap and atrophic fracture ends, a small amount or even no callus formation
• Histological examination reveals that the gap at the fracture ends is filled with fibrous tissue without osteogenic activity
• Age of 18-70 years

Exclusion Criteria:

• The underlying disease that affects wound healing, such as diabetes, hematological system diseases, immune diseases, connective tissue diseases
• Pregnancy or lactation
• Heart, lung, liver, and kidney dysfunction
• Participate in other clinical trials

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
Experimental: control group; Patients with atrophic nonunion of femoral shaft fractures are equally and randomly assigned to control group, which received conventional surgery.	Procedure: conventional surgery; Patients with atrophic nonunion of femoral shaft fractures are equally and randomly assigned to control group, which received conventional surgery.; Other Names: control group
Experimental: experimental group; Patients with atrophic nonunion of femoral shaft fractures are equally and randomly assigned to experimental group, which are injected with autologous platelet-rich plasma on the basis of conventional surgery.	Procedure: autologous platelet-rich plasma; Patients with atrophic nonunion of femoral shaft fractures are equally and randomly assigned to experimental group, which are injected with autologous platelet-rich plasma on the basis of conventional surgery.; Other Names: experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fracture healing rate	To assess the condition of fracture healing. The disunion was identified if the fracture was not healed at postoperative 9 months. Fracture healing includes clinical healing and bone healing.	month 9 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analogue scale scores	Visual analogue scale is a method to assess pain intensity. Using a ruler with 10 scales, the ends are 0 and 10, respectively. 0 represents no pain; 10 represents the most unbearable severe pain.	changes of baseline and month 3, month 6, month 9, month 12 after surgery

Collaborators and Investigators

• Sponsor: Qinghai University
• Investigators: Principal Investigator: Zichun Zhao, bachelor, Affiliated Hospital of Qinghai University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Ununited
• Other Study ID Numbers: QinghaiUH_008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No