Efficacy and Safety Study of Non-percutaneous Vertebroplasty With Macroporous Calcium Phosphate Cement (MCPC)

Study Overview
=================
Brief Summary
-----------------
The macroporous calcium phosphate cement, MCPC, which composition is close to bone, is malleable and biocompatible, and has intrinsic radio opacity and good ability to undergo mechanical constraints. After the filling of the bone cavity, the cement hardens. Interestingly, this calcium phosphate cement has no exothermic hardening (on the contrary, the ordinary cements used nowadays cause necrotic lesions in tissues around during this phase) and favours vascularisation, cellular colonisation and bone healing. Thanks to its resorbability, the MCPC cement is replaced little by little by a physiologic bone. This last property is very important for young people needing a vertebroplasty after a traumatism. Thus, it will be tested in a low-invasive surgery, a non-percutaneous vertebroplasty, consisting in filling with the MCPC the body of the broken vertebra, after its stabilization thanks to 4 interpedicular screws. This protocol will be proposed to patients 1 to 3 weeks after the trauma having caused the fracture. The follow up will last 12 months with 5 visits (2 days, and 3, 4, 6 and 12 months after vertebroplasty), 2 CT scanners before inclusion and at 12 months, 2 EOS (ultra low dose imager replacing classical radiography) at 5 and 12 months, questionnaires (visual analogic scale for pain, and quality of life with OSWESTRY and SF36 scales) before inclusion and at 2 days, and 3, 4, 6 and 12 months, and biological exams (CRP/VS, for inflammation) at each visit except 2 days after surgery. An osteodensitometry will be performed at 3 months.

Detailed Description
-----------------
The macroporous calcium phosphate cement, MCPC, which composition is closer to bone than acrylic cement, is malleable and biocompatible, and has intrinsic radio opacity and good biomechanical properties (12 +/- 3 Mpa in 24 hours). After the filling of the bone cavity, the cement hardens in situ thanks to hydrolysis and apatite precipitation. Interestingly, this calcium phosphate cement has no exothermic hardening (on the contrary, the PMMA causes necrotic lesions in tissues around during this phase). During the dissolution, a macroporosity takes form between biphasic calcium phosphate granules. That permits vascularisation, cellular colonisation and bone healing. Thanks to its resorbability, the MCPC cement is replaced by a physiologic tissue. This last property is very important for young people needing a vertebroplasty after a traumatism. The issue is to validate this biomaterial with appropriate mechanical, biocompatibility properties and intrinsic radio opacity, and that can favour bone regeneration, with a lower frequency of leak and risk enhancement of other vertebra fracture. The MCPC will thus be tested on few patients to assess its efficacy and security for bone filling in vertebra site. Thus, it will be used in a low-invasive surgery, a non-percutaneous vertebroplasty, consisting in filling with the MCPC the body of the broken vertebra, after its stabilization thanks to 4 interpedicular screws. This protocol will be proposed to 21 patients 1 to 3 weeks after the trauma having caused the fracture. The follow up will last 12 months with 5 visits.

Official Title
-----------------
Non Comparative, Monocentric, Prospective, Phase II, Study of Calcium Phosphate Cement MCPC Efficacy and Safety for Bone Filling in Vertebral Site

Conditions
-----------------
Vertebra Trauma

Intervention / Treatment
-----------------
* Procedure: non percutaneous vertebroplasty


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged between 18 and 65 years old, BMI < 30 Stable and important fracture of the vertebral body between T9 and L5 Diagnostic maximum 3 weeks after the trauma causing the fracture Type A1 to A3 (MAGERL scale) assessed by CT scan Lumbar local traumatic angle > 10°, and thoracic > 15° Given informed consent Patient with French health system Exclusion Criteria: For women: no efficient contraception (intra uterine device, or contraceptive pill) Pregnant or feeding women Fractures due to metastasis or multiple myeloma Symptomatic compression of the spinal cord Multi site vertebroplasty Scoliosis with a Cobb angle > 20° Surgery zone local infection All surgical contraindications Immune system abnormalities, immune deficiency or suppression, HIV or BHV or CHV (positive serology) Severe hyperparathyroidism: calcium > 2,45 mmol/l and [PTH] ≥ 50pg / ml Uncontrolled diabetes (untreated or non stabilized by treatment) Long corticoid treatment (more than 6 months and stopped since less than 3 months) Chemotherapy All contra indication to MCPC: osteomyelitis, bone degenerative disease or necrosis of surgery site. Known allergy to indigotine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Procedure: non percutaneous vertebroplasty<br>* The patient will undergo general anaesthetic. With a low invasive approach, 4 screws will be placed in pedicles of vertebra under and above the fractured vertebra. The reduction of the fracture will be realised by a smooth movement, and screws positions will be verified by a radio control, with a guided navigation system. The stems will be placed and locked. After the screw positioning, the fractured vertebra pedicles will be reached by a low invasive approach, using a 6 mm trocar, to raise, if necessary, the vertebral plate. Then the cement will be injected in the vertebral body, under radio control. When the maximal volume (6 to 8 ml) is reached, or if an extra vertebral leak is detected, the cement injection is stopped. Then the incision is closed. The next day, the patient will be placed in a corset for a 2 months period.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficiency of non-percutaneous vertebroplasty using MCPC, in 18 to 65 years old patients, after a huge trauma, will be evaluated based on evaluation of the vertebra height by measuring local traumatic angle. |  | At the 4th month after the surgical procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of Severe Adverse Events frequency (cement leak, new fractures, late huge loss of vertebra height) and inflammatory response |  | before inclusion and at 3 months, 4 months, 5 months, 12 months | 
| Pain intensity: difference between before inclusion and during follow up. Evaluation with Visual Analogic Scale. |  | before inclusion and at 2 days, and 3, 4, 6 and 12 months | 
| Quality of life: difference between before inclusion and during follow up. Evaluation with OSWESTRY and SF 36 scales. |  | before inclusion and at 2 days, and 3, 4, 6 and 12 months. | 
| The evolution of bone formation and MCPC resorption: quantification of bone reconstruction. |  | CT scan at 6 and 12 months after surgery, and with osteodensitometry at 3 months after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vertebroplasty, spine, vertebra height, adverse events, calcium phosphate bone cement