FARE Augmentation of Proximal Femoral Fractures With CaS/HA and Systemic ZA

Sponsor

Aksaray University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06135298

Collaborator

Lund University Hospital (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to investigate the new bone formation around a metal device in the femoral head in patients with osteoporotic hip fractures undergoing surgical treatment with nails. These surgeries have a high risk of fixation failure in patients with osteoporosis due to low bone quality. The main question we aim to answer are whether promoting new bone formation around the implant is possible with a bone graft substitute (CERAMENT™ Bone Void Filler) and systemic osteoporosis drug (zoledronic acid) combination, which can strengthen the surgical fixation of the fracture. Participants will consist of patients suffering hip fracture and already scheduled for surgical treatment with a nail. One group will undergo conventional surgery. While the other group will also undergo the same surgery, they will receive CERAMENT™ Bone Void Filler around the implant as a short, extra step during surgery. This will allow the researchers to see whether new bone is formed during a 6-month follow-up.

Condition or Disease	Intervention/Treatment	Phase
Trochanteric Fracture of Femur Osteoporotic Fracture of Femur Hip Fractures Bone Density, Low	Procedure: OSTEOSYNTHESIS Drug: Zoledronic acid Device: CERAMENT BONE VOID FILLER (BVF)	Phase 4

Detailed Description

A total of 20 eligible patients with osteoporotic per trochanteric fractures, that are treated with proximal femoral nail (PFN), will be included in the study after informed and approved consent and will be randomized into two groups. Randomization will be performed by the principal investigator, by sealed envelopes, after determining if the patient fulfills the inclusion criteria.

Following randomization, all patients will be operated with PFN. The control group will receive a standard surgical procedure without augmentation of the helical blade. The study group will also receive 2-3 mL of CERAMENT™ BONE VOID FILLER (510(k) Number K201535) delivered using an introducer needle inserted through the helical blade of the PFN inserted in the femoral head, away from the fracture site, with an intent to increase bone-implant anchorage.

Routine procedure for anesthesia and infection prophylaxis according to written instructions will be followed in every patient. As an additional infection antibiotic prophylaxis all patients will receive a 2nd generation tetracycline i.e. Doxycycline 200 mg Oral dose 4 h before the start of surgery. The patient will be operated supine with the fractured leg positioned in traction table. In the standard protocol, fluoroscopy is used to get AP and lateral view during surgery. The hip region is scrubbed and dressed in sterile drapes. Using standard technique, a nail is inserted into the intramedullary canal after fracture reduction. To insert the helical blade in the femoral neck, 2.0 mm diameter guide wire is first placed in the femoral neck, checking the fluoroscopic AP and lateral views. The canal is opened using a 10 mm drill bit and the length of helical blade is measured.

After the pilot hole is created for the helical blade placement, the hollow helical blade will be inserted partially with gentle blows with a hammer, 2.5 cm from its final intended position. At this point, the injectable CaS/HA biomaterial will be mixed as per the manufacturer guidelines and the paste will be transferred into an injection syringe. At t = 2.5 min from the start of mixing, 2-3 mL of bone void filler (BVF) paste will be injected by a CE marked Introducer Needle connected to the injection syringe, through the hollow helical blade. Under fluoroscopic guidance, injection will start proximal and continue while the cannula is slowly retracted towards the tip of the helical blade until the drilled space in front of the lag screw and the surrounding cancellous bone is filled with 2-3 mL of the material. Finally, the helical blade will be inserted to its end position with gentle blows with a hammer. Remaining material approximately 2 mL still being moldable will be manually deposited in the trochanteric fracture void. A very similar injection technique for application in a dynamic hip screw (DHS) in trochanteric fractures is described in a recently published scientific article.

Patients with an osteoporotic trochanteric femoral fracture that have no contraindications should receive secondary fracture prevention with a bisphosphonate. In this study, all patients will receive systemic (Intravenous) Zoledronic acid (ZA) as routine. All patients included in the study without any contraindication for ZA, therefore will receive 5mg/100ml ZA intravenously day 5 after surgery, during hospitalization. ZA has been shown to significantly reduce the risk of hip fracture in post-menopausal women.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A total of 20 eligible patients with osteoporotic per trochanteric fractures, that are scheduled to be treated with proximal femoral nail (PFN), will be included in the study after informed and approved consent and will be randomized into two groups. Randomization will be performed by the principal investigator, by sealed envelopes, after determining if the patient fulfills the inclusion criteria.A total of 20 eligible patients with osteoporotic per trochanteric fractures, that are scheduled to be treated with proximal femoral nail (PFN), will be included in the study after informed and approved consent and will be randomized into two groups. Randomization will be performed by the principal investigator, by sealed envelopes, after determining if the patient fulfills the inclusion criteria.

Masking:

Double (Participant, Investigator)

Masking Description:

Patients in the study group and the control group will be blind to the group they are assigned to until the end of the trial. As intervention is performed during the surgery, blinding will not be possible for the surgical team. Investigators will be blinded during all evaluations, however due to radio-opaque nature of CERAMENT™ BVF, detection of intervention group is possible in CT, DEXA and X-ray evaluations.

Primary Purpose:

Treatment

Official Title:

Augmentation of Pertrochanteric Fracture Proximal Femoral Nail Osteosynthesis Using Calcium Sulphate/Hydroxyapatite Combined With Systemic Bisphosphonate - A Pilot Study of the FARE (Fracture Anchorage and Bone REgeneration) Method

Anticipated Study Start Date :

Nov 15, 2023

Anticipated Primary Completion Date :

Nov 15, 2024

Anticipated Study Completion Date :

May 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: OSTEOSYNTHESIS + SYSTEMIC ZOLEDRONIC ACID After osteosynthesis, systemic Zoledronic acid 5mg will be given intravenously at day 5 after surgery, during hospitalization.	Procedure: OSTEOSYNTHESIS Routine procedure for anesthesia and infection prophylaxis according to written instructions will be followed in every patient. The patient will be operated supine with the fractured leg positioned in traction table. The hip region is scrubbed and dressed in sterile drapes. Using standard technique, a nail is inserted into the intramedullary canal after fracture reduction. To insert the helical blade in the femoral neck, 2.0 mm diameter guide wire is first placed in the femoral neck, checking the fluoroscopic AP and lateral views. The canal is opened using a 10 mm drill bit and the length of helical blade is measured. After the pilot hole is created for the helical blade placement, the hollow helical blade will be inserted to its end position with gentle blows with a hammer. Other Names: Proximal femoral nail with helical blade Drug: Zoledronic acid Zoledronic acid (ZA), is a bisphosphonate, and has been shown to reduce the risk of hip fracture by 41% in post-menopausal women. For systemic injection, 5 mg (as per clinical protocol) will be injected intravenously 5 days after surgery, during hospitalization. Other Names: Ronidro 5mg/Bag 100 mL Inj
Experimental: OSTEOSYNTHESIS + LOCAL CERAMENT BONE VOID FILLER (BVF) + SYSTEMIC ZOLEDRONIC ACID During osteosynthesis, cerament BVF will be used for the augmentation of the helical blade. Then, systemic Zoledronic acid 5mg will be given intravenously at day 5 after surgery, during hospitalization.	Procedure: OSTEOSYNTHESIS Routine procedure for anesthesia and infection prophylaxis according to written instructions will be followed in every patient. The patient will be operated supine with the fractured leg positioned in traction table. The hip region is scrubbed and dressed in sterile drapes. Using standard technique, a nail is inserted into the intramedullary canal after fracture reduction. To insert the helical blade in the femoral neck, 2.0 mm diameter guide wire is first placed in the femoral neck, checking the fluoroscopic AP and lateral views. The canal is opened using a 10 mm drill bit and the length of helical blade is measured. After the pilot hole is created for the helical blade placement, the hollow helical blade will be inserted to its end position with gentle blows with a hammer. Other Names: Proximal femoral nail with helical blade Drug: Zoledronic acid Zoledronic acid (ZA), is a bisphosphonate, and has been shown to reduce the risk of hip fracture by 41% in post-menopausal women. For systemic injection, 5 mg (as per clinical protocol) will be injected intravenously 5 days after surgery, during hospitalization. Other Names: Ronidro 5mg/Bag 100 mL Inj Device: CERAMENT BONE VOID FILLER (BVF) In addition to the standard surgical procedure, in the study group, after creating the canal with 10 mm drill bit and partly insertion of the helical blade, the synthetic bone void filler CaS/HA will be injected. The helical blade will be inserted partially with gentle blows with a hammer, 2.5 cm from its final intended position. The injectable CaS/HA biomaterial will be mixed as per the manufacturer guidelines and the paste will be transferred into an injection syringe. At t = 2.5 min from the start of mixing, 2-3 mL of BVF paste will be injected by a CE marked Introducer Needle connected to the injection syringe, through the hollow helical blade. Finally, the helical blade will be inserted to its end position with gentle blows with a hammer. Remaining material approximately 2 mL still being moldable will be manually deposited in the trochanteric fracture void. Other Names: CaS/HA

Arm

Intervention/Treatment

Active Comparator: OSTEOSYNTHESIS + SYSTEMIC ZOLEDRONIC ACID

After osteosynthesis, systemic Zoledronic acid 5mg will be given intravenously at day 5 after surgery, during hospitalization.

Procedure: OSTEOSYNTHESIS

Routine procedure for anesthesia and infection prophylaxis according to written instructions will be followed in every patient. The patient will be operated supine with the fractured leg positioned in traction table. The hip region is scrubbed and dressed in sterile drapes. Using standard technique, a nail is inserted into the intramedullary canal after fracture reduction. To insert the helical blade in the femoral neck, 2.0 mm diameter guide wire is first placed in the femoral neck, checking the fluoroscopic AP and lateral views. The canal is opened using a 10 mm drill bit and the length of helical blade is measured. After the pilot hole is created for the helical blade placement, the hollow helical blade will be inserted to its end position with gentle blows with a hammer.

Other Names:

Proximal femoral nail with helical blade

Drug: Zoledronic acid

Zoledronic acid (ZA), is a bisphosphonate, and has been shown to reduce the risk of hip fracture by 41% in post-menopausal women. For systemic injection, 5 mg (as per clinical protocol) will be injected intravenously 5 days after surgery, during hospitalization.

Other Names:

Ronidro 5mg/Bag 100 mL Inj

Experimental: OSTEOSYNTHESIS + LOCAL CERAMENT BONE VOID FILLER (BVF) + SYSTEMIC ZOLEDRONIC ACID

During osteosynthesis, cerament BVF will be used for the augmentation of the helical blade. Then, systemic Zoledronic acid 5mg will be given intravenously at day 5 after surgery, during hospitalization.

Procedure: OSTEOSYNTHESIS

Other Names:

Proximal femoral nail with helical blade

Drug: Zoledronic acid

Other Names:

Ronidro 5mg/Bag 100 mL Inj

Device: CERAMENT BONE VOID FILLER (BVF)

In addition to the standard surgical procedure, in the study group, after creating the canal with 10 mm drill bit and partly insertion of the helical blade, the synthetic bone void filler CaS/HA will be injected. The helical blade will be inserted partially with gentle blows with a hammer, 2.5 cm from its final intended position. The injectable CaS/HA biomaterial will be mixed as per the manufacturer guidelines and the paste will be transferred into an injection syringe. At t = 2.5 min from the start of mixing, 2-3 mL of BVF paste will be injected by a CE marked Introducer Needle connected to the injection syringe, through the hollow helical blade. Finally, the helical blade will be inserted to its end position with gentle blows with a hammer. Remaining material approximately 2 mL still being moldable will be manually deposited in the trochanteric fracture void.

Other Names:

CaS/HA

Outcome Measures

Primary Outcome Measures

Change of bone density around the helical blade of proximal femoral nail [1-week and 6 months after the surgery]
Change of bone density measured by Dual-energy X-ray absorptiometry (DEXA) scan of bilateral proximal femurs will be evaluated. A 10 % increase in bone density / bone volume in the femoral head adjacent to the helical blade is expected to be significant and clinically relevant.
Bone remodeling around the helical blade of proximal femoral nail [1-week and 6 months after the surgery]
Bone remodeling around the helical blade will be evaluated by computerized tomography (CT) scan of the pelvis using a program for alleviating metal artefacts. A 10 % increase in bone density / bone volume in the femoral head adjacent to the helical blade is expected to be significant and clinically relevant.

Secondary Outcome Measures

Harris Hip Score [1-week and 6 months after the surgery]
The Harris Hip Score (HHS) has a maximum of 100 points (best possible outcome) covering pain (1 item, 0-44 points), function (7 items, 0-47 points), absence of deformity (1 item, 4 points), and range of motion (2 items, 5 points). The higher the HHS, the less dysfunction. A total score of <70 is considered a poor result; 70-80 is considered fair, 80-90 is good, and 90-100 is an excellent result.
Screw position and migration by X-ray [1-week and 6 months after the surgery]
X-ray evaluation will quantify helical blade migration on anteroposterior (AP) radiographs by two investigators independently, accounting for femoral rotation and flexion.
Evaluation of fracture union [6 months after the surgery]
Radiographic evaluation will be performed by two investigators independently to decide whether fracture fixation resulted with union or non-union.
Any mechanical complications [6 months after the surgery]
Any mechanical complications related to the implant will be recorded.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Being between 65-90 years of age at the time of fracture
Acute, unilateral proximal hip fracture (AO Foundation/Orthopaedic Trauma Association [AO/OTA]: A1 and A2) caused by low energy trauma
Physical condition eligible for surgery with proximal femoral nail
Having low mortality and high fracture risk according to Fracture and Mortality Risk Evaluation Index (FAME) classification
Patient with communicative ability to understand the procedure and participate in the study and the follow-up program, consented to be included in the study and signed the consent form

Exclusion Criteria:

Previous hip or pelvis fracture on the same side
Concurrent corticosteroid treatment
Concurrent medical osteoporosis treatment
Irreversible coagulopathy or bleeding disorder.

o Note regarding reversible coagulopathies: Patients on coumadin or other anticoagulants may participate. Investigators will follow routine practices for perioperative discontinuation and re-initiation of anti-coagulants.

Concurrent dialysis or elevated creatinine
Presence of hypo- or hyper calcaemia
History or active treatment due to malignancy involving the pelvis/hip area, including ongoing or completed radiotherapy
Fractures involving acetabulum
Active systemic infection or local skin infection at the incision site
Known hyperthyroidism or thyroid adenoma,
History of serious reaction to iodine-based radio contrast agents
Patient without communicative ability to understand the procedure and participate in the study and the follow-up program, did not consent to be included in the study and/or did not sign the consent form