Freeze-dried Bovine Hydroxyapatite/Secretome Composite for Bone Defects

Bone Loss Clinical Trial

Official title:

Clinical Trial of Freeze-dried Bovine Hydroxyapatite/Secretome Composite Application for the Management of Long Bone Defects in the Lower Extremities

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04980261
• Other study ID #: 0045/KEPK/VIII/2020
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: April 2021
• Source: Dr. Soetomo General Hospital
• Contact: Ferdiansyah Mahyudin, MD, Ph.D
• Phone: +62811320635
• Email: ferdyortho[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial aims to investigate the efficacy of freeze-dried bovine hydroxyapatite/secretome composite application for the management of long bone defects and other bone healing disorders in the lower extremities.

Description:

The gold standard for treating bone defect conditions is autologous bone graft (autograft). Autograft promotes bone healing due to its osteoconductive (serving as a foundation that facilitates bone growth), osteoinductive (stimulates progenitor cells), and osteogenesis (acting as a precursor of osteoblasts and osteoclasts) properties. However, donor site morbidity and persisting pain following harvest remains a major problem. Hence, we attempt to investigate the efficacy of other bone substitutes, i.e., bovine hydroxyapatite/secretome composite, to treat long bone defects and other bone healing disorders in the lower extremities.

Bovine hydroxyapatite (BHA) is a xenograft (animal-derived graft) with osteoconductive properties. Simultaneously, the secretome of the mesenchymal stem cells contains cytokines, chemokines, and growth factors, which possess osteoinductive properties. Thus, we hypothesize that the combination (composite) of BHA/secretome (in the form of freeze-dried (FD) BHA/secretome composite) will promote bone healing ability that is equal to autografts while eliminating donor-site morbidity in the patient.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: December 31, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Patients presenting with bone defects (less than 5 cm) in the diaphysis of the long bones of the lower extremities due to trauma and other bone healing disorders

• No history of comorbid diseases

• Willing to be involved in the clinical trial

Exclusion Criteria:

• Patients with bone defects or impaired bone healing caused by tumors, infections, and metabolic diseases

• Suffered from multiple fractures and multitrauma patients

• Loss to follow-up

Related Conditions & MeSH terms

• Bone Loss

Intervention

Procedure:
• ORIF + autograft
Patients will undergo a standard open reduction internal fixation (ORIF) procedure with autograft implantation (from the iliac crest).
• ORIF + FD BHA/Secretome
Patients will undergo an ORIF procedure and subsequently receive freeze-dried bovine hydroxyapatite/secretome composite implantation.

Locations

Country	Name	City	State
Indonesia	Dr. Soetomo General Hospital	Surabaya	East Java

Sponsors (5)

Lead Sponsor	Collaborator
Dr. Soetomo General Hospital	Airlangga University Hospital, Cell & Tissue Bank, Dr. Soetomo General Hospital, Dr. Ramelan Naval Hospital, Sidoarjo General Hospital

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	X-ray evaluation immediately following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	Day-0
Primary	X-ray evaluation at 4 weeks following surgery	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	4 weeks
Primary	X-ray evaluation at 8 weeks following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	8 weeks
Primary	X-ray evaluation at 12 weeks following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	12 weeks
Primary	X-ray evaluation at 16 weeks following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	16 weeks
Primary	Ultrasonography evaluation at 2 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	2 weeks
Primary	Ultrasonography evaluation at 4 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	4 weeks
Primary	Ultrasonography evaluation at 8 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	8 weeks
Primary	Ultrasonography evaluation at 12 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	12 weeks
Primary	Ultrasonography evaluation at 16 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	16 weeks
Secondary	Functional evaluation at 8 weeks following surgery.	The functional evaluation will be assessed by using a scoring system named LEFS (Lower Extremity Functional Scale). LEFS is a widely known and validated patient-reported outcome measures (PROM) comprising 20 questions that is used to assess lower extremity functions. The patients will be asked to rate the activity listed from 0 to 4 (0 refers to an extreme difficulty/unable to perform activity, while 4 refers to having no difficulty at all). A higher score (maximum 80 points) indicates a very high function (i.e., a more favorable outcome).	8 weeks
Secondary	Functional evaluation at 12 weeks following surgery.	The functional evaluation will be assessed by using a scoring system named LEFS (Lower Extremity Functional Scale). LEFS is a widely known and validated patient-reported outcome measures (PROM) comprising 20 questions that is used to assess lower extremity functions. The patients will be asked to rate the activity listed from 0 to 4 (0 refers to an extreme difficulty/unable to perform activity, while 4 refers to having no difficulty at all). A higher score (maximum 80 points) indicates a very high function (i.e., a more favorable outcome).	12 weeks
Secondary	Functional evaluation at 16 weeks following surgery.	The functional evaluation will be assessed by using a scoring system named LEFS (Lower Extremity Functional Scale). LEFS is a widely known and validated patient-reported outcome measures (PROM) comprising 20 questions that is used to assess lower extremity functions. The patients will be asked to rate the activity listed from 0 to 4 (0 refers to an extreme difficulty/unable to perform activity, while 4 refers to having no difficulty at all). A higher score (maximum 80 points) indicates a very high function (i.e., a more favorable outcome).	16 weeks