Investigating Bone Cement With or Without Inossia™ Cement Softener for Vertebral Compression Fractures

Vertebral Compression Fracture Clinical Trial

— SOFTBONE  

Official title:

A Multicentre, Single-blind, RCT to Document the Safety and Efficacy of the Use of a Bone Cement With or Without Inossia™ Cement Softener for Patients With Vertebral Compression Fractures

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05676320
• Other study ID #: SOFTBONE 1512:1
• Status: Recruiting
• Phase: N/A
• Start date: March 11, 2021
• Est. completion date: December 2025

Study information

• Verified date: December 2022
• Source: Inossia AB
• Contact: Malin K Nilsson, PhD
• Phone: +46702688674
• Email: malin.nilsson[@]inossia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall purpose of conducting this study is to evaluate the safety and efficacy of V-Flex and V-Steady for augmentation of osteoporotic vertebral compression fractures and to verify that adding a cement softener into a PMMA bone cement is comparable to a PMMA bone cement alone (V-Steady).

Description:

The clinical investigation is a prospective, single-blind, controlled multi-center study of vertebral compression fractures treated by vertebroplasty or kyphoplasty with PMMA alone (V-Steady) or PMMA mixed with Inossia™ Cement Softener (V-Flex).

The overall purpose of conducting this study is to confirm the safety and efficacy of Inossia™ Cement Softener mixed with PMMA for augmentation of osteoporotic vertebral compression fractures and to verify that the V-Flex is, at least, comparable (non-inferior) to the PMMA products used today.

All eligible patients will be invited to participate in the study. A total of 150 patients will be enrolled in the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent obtained before any study-related activities (study-related activities are any procedures that would not have been performed during normal management of the patient, i.e. standard of care);

• Symptomatic osteoporotic vertebral compression fracture without prior or not responding to medical treatment within 6 months;

• Maximum of 1 level of vertebral compression fractures eligible for treatment localized at level Th5 to L5 and verified by MRI or bone scan;

• Height reduction of the affected vertebra(e) with an anterior wall compression of not exceeding 60% compared to the nearest normal vertebral body determined by X-ray;

• Have pain correlating to the fractured levels requiring regular analgesic intake and/or causing substantial disability of daily life;

• Pain score = 40 mm measured by VAS correlating to at least one of the fracture levels (scale 0 - 100 mm) at the screening visit;

• Oswestry Disability Index > 20 (0 - 100 scale);

• SF-12PCS Index < 80 (0 - 100 scale);

• Patient with a communicative ability to understand the procedure and participate in the study and comply with the follow up program.

Exclusion Criteria:

• Patients below 18 years;

• Any burst fracture;

• Unstable fractures defined by neurological deficit or interspinous process widening as evaluated by the Investigator, as well as kyphosis > 30°, translation > 4 mm;

• Established or suspected malignancy of the fractured vertebra. Hemangioma of the fractured vertebra;

• High energy trauma or clinical diagnosis of herniated nucleus pulposus or severe spinal stenosis as suggested by progressive weakness;

• Have neurologic symptoms or deficits, or radiculopathy related to the fractured vertebrae;

• Patients with extremely high BMI, i.e. BMI = 40;

• Previously treated with vertebroplasty or kyphoplasty;

• Patients with concomitant diseases which may be worsened by invasive treatment of the fracture such as e.g. severe cardiopulmonary dysfunction (including aortic aneurysm), as judged by the Investigator

• Irreversible coagulopathy or bleeding disorder. Note regarding reversible coagulopathies: Patients on Coumadin or other anticoagulants may participate. Investigators should follow routine practices for perioperative discontinuation and re- initiation of anticoagulants;

• Active systemic infection or local skin infection at the puncture site;

• Pregnancy or breast-feeding;

• Patients with known chemical dependency or drugs or with a medical history of drug abuse;

• Patients who are serving prison sentence;

• Have participated in another investigational study within 30 days prior to inclusion

• Pacemaker

• Previous or active radiotherapy affecting the spine

Related Conditions & MeSH terms

• Fractures, Bone
• Fractures, Compression
• Vertebral Compression Fracture

Intervention

Device:
• V-Flex
Bone cement including Inossia Cement Softener. Treatment for vertebral compression fracture
• V-Steady
Bone Cement alone

Locations

Country	Name	City	State
Canada	Beam Radiology	Calgary	Alberta
Germany	Mannheim University Hospital	Mannheim
Germany	Hospital in Mechernich	Mechernich
Poland	Lodz University Hospital	Lódz
Spain	Clínico San Carlos	Madrid
Spain	Puerta de Hierro	Madrid
Spain	University Hospital in Valladolid	Valladolid

Sponsors (3)

Lead Sponsor	Collaborator
Inossia AB	EIT Health, Uppsala University

Countries where clinical trial is conducted

Canada,  Germany,  Poland,  Spain, 

References & Publications (38)

Clauss W. How big is the risk of an examination with x-ray contrast media of patients with known hypersensitivity to CM and for allergic patients? In Dawson P and Clauss W (eds.): Contrast media in practice, 2nd edition, Springer-Verlag, Berlin-Heidelberg, 1999:98-99.

Clinical Trial Considerations:Vertebral Augmentation Devices to Treat Spinal lnsufficiency Fractures, October 24, 2004.

Code of Federal Regulations. Title 21, Volume 8. Part 812, Investigational Device Exemptions, Revised 2006.

Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ 3rd. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993 May 1;137(9):1001-5. doi: 10.1093/oxfordjournals.aje.a116756. — View Citation

Cooper C, Atkinson EJ, O'Fallon WM, Melton LJ 3rd. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res. 1992 Feb;7(2):221-7. doi: 10.1002/jbmr.5650070214. — View Citation

Cortet B, Cotten A, Boutry N, Flipo RM, Duquesnoy B, Chastanet P, Delcambre B. Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: an open prospective study. J Rheumatol. 1999 Oct;26(10):2222-8. — View Citation

de Bruin TW. Iodide-induced hyperthyroidism with computed tomography contrast fluids. Lancet. 1994 May 7;343(8906):1160-1. doi: 10.1016/s0140-6736(94)90265-8. No abstract available. — View Citation

Do HM, Kim BS, Marcellus ML, Curtis L, Marks MP. Prospective analysis of clinical outcomes after percutaneous vertebroplasty for painful osteoporotic vertebral body fractures. AJNR Am J Neuroradiol. 2005 Aug;26(7):1623-8. — View Citation

Eck JC, Nachtigall D, Humphreys SC, Hodges SD. Comparison of vertebroplasty and balloon kyphoplasty for treatment of vertebral compression fractures: a meta-analysis of the literature. Spine J. 2008 May-Jun;8(3):488-97. doi: 10.1016/j.spinee.2007.04.004. Epub 2007 May 29. — View Citation

Fairbank JC, Pynsent PB. The Oswestry Disability Index. Spine (Phila Pa 1976). 2000 Nov 15;25(22):2940-52; discussion 2952. doi: 10.1097/00007632-200011150-00017. — View Citation

Gaughen JR Jr, Jensen ME, Schweickert PA, Kaufmann TJ, Marx WF, Kallmes DF. Lack of preoperative spinous process tenderness does not affect clinical success of percutaneous vertebroplasty. J Vasc Interv Radiol. 2002 Nov;13(11):1135-8. doi: 10.1016/s1051-0443(07)61955-1. — View Citation

Gill JB, Kuper M, Chin PC, Zhang Y, Schutt R Jr. Comparing pain reduction following kyphoplasty and vertebroplasty for osteoporotic vertebral compression fractures. Pain Physician. 2007 Jul;10(4):583-90. — View Citation

Grados F, Depriester C, Cayrolle G, Hardy N, Deramond H, Fardellone P. Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty. Rheumatology (Oxford). 2000 Dec;39(12):1410-4. doi: 10.1093/rheumatology/39.12.1410. — View Citation

Guidance Document for the Preparation of IDEs for Spinal Systems, January 13, 2000.

ICH Harmonised Tripartite Guideline. Statistical principles for clinical trials. International Conference on Harmonisation E9 Expert Working Group. Stat Med. 1999 Aug 15;18(15):1905-42. No abstract available. — View Citation

International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals. N Engl J Med. 1997 Jan 23;336(4):309-15. doi: 10.1056/NEJM199701233360422. No abstract available. — View Citation

International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Good Clinical Practice. 1-5-1996.

Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med. 1999 Jun 14;159(11):1215-20. doi: 10.1001/archinte.159.11.1215. — View Citation

Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology. 1990 Jun;175(3):621-8. doi: 10.1148/radiology.175.3.2343107. — View Citation

Kim CW, Minocha J, Wahl CE, Garfin SR. Response of fractured osteoporotic bone to polymethylacrylate after vertebroplasty: case report. Spine J. 2004 Nov-Dec;4(6):709-12. doi: 10.1016/j.spinee.2004.05.002. — View Citation

Lane JI, Maus TP, Wald JT, Thielen KR, Bobra S, Luetmer PH. Intravertebral clefts opacified during vertebroplasty: pathogenesis, technical implications, and prognostic significance. AJNR Am J Neuroradiol. 2002 Nov-Dec;23(10):1642-6. — View Citation

Layton KF, Thielen KR, Koch CA, Luetmer PH, Lane JI, Wald JT, Kallmes DF. Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications. AJNR Am J Neuroradiol. 2007 Apr;28(4):683-9. — View Citation

Leidig G, Minne HW, Sauer P, Wuster C, Wuster J, Lojen M, Raue F, Ziegler R. A study of complaints and their relation to vertebral destruction in patients with osteoporosis. Bone Miner. 1990 Mar;8(3):217-29. doi: 10.1016/0169-6009(90)90107-q. — View Citation

McKiernan F, Faciszewski T, Jensen R. Quality of life following vertebroplasty. J Bone Joint Surg Am. 2004 Dec;86(12):2600-6. doi: 10.2106/00004623-200412000-00003. — View Citation

Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med. 1998 May 15;128(10):793-800. doi: 10.7326/0003-4819-128-10-199805150-00001. — View Citation

Palussiere J, Berge J, Gangi A, Cotten A, Pasco A, Bertagnoli R, Jaksche H, Carpeggiani P, Deramond H. Clinical results of an open prospective study of a bis-GMA composite in percutaneous vertebral augmentation. Eur Spine J. 2005 Dec;14(10):982-91. doi: 10.1007/s00586-003-0664-2. Epub 2005 Jun 2. — View Citation

Prather H, Van Dillen L, Metzler JP, Riew KD, Gilula LA. Prospective measurement of function and pain in patients with non-neoplastic compression fractures treated with vertebroplasty. J Bone Joint Surg Am. 2006 Feb;88(2):334-41. doi: 10.2106/JBJS.D.02670. — View Citation

Silverman SL, Minshall ME, Shen W, Harper KD, Xie S; Health-Related Quality of Life Subgroup of the Multiple Outcomes of Raloxifene Evaluation Study. The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum. 2001 Nov;44(11):2611-9. doi: 10.1002/1529-0131(200111)44:113.0.co;2-n. — View Citation

Trout AT, Gray LA, Kallmes DF. Vertebroplasty in the inpatient population. AJNR Am J Neuroradiol. 2005 Aug;26(7):1629-33. — View Citation

Trout AT, Kallmes DF, Gray LA, Goodnature BA, Everson SL, Comstock BA, Jarvik JG. Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire. AJNR Am J Neuroradiol. 2005 Nov-Dec;26(10):2652-7. — View Citation

Trout AT, Kallmes DF, Kaufmann TJ. New fractures after vertebroplasty: adjacent fractures occur significantly sooner. AJNR Am J Neuroradiol. 2006 Jan;27(1):217-23. — View Citation

Uppin AA, Hirsch JA, Centenera LV, Pfiefer BA, Pazianos AG, Choi IS. Occurrence of new vertebral body fracture after percutaneous vertebroplasty in patients with osteoporosis. Radiology. 2003 Jan;226(1):119-24. doi: 10.1148/radiol.2261011911. — View Citation

Vogl TJ, Proschek D, Schwarz W, Mack M, Hochmuth K. CT-guided percutaneous vertebroplasty in the therapy of vertebral compression fractures. Eur Radiol. 2006 Apr;16(4):797-803. doi: 10.1007/s00330-005-0021-4. Epub 2005 Dec 7. — View Citation

Voormolen MH, Mali WP, Lohle PN, Fransen H, Lampmann LE, van der Graaf Y, Juttmann JR, Jansssens X, Verhaar HJ. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR Am J Neuroradiol. 2007 Mar;28(3):555-60. — View Citation

Voormolen MH, van Rooij WJ, Sluzewski M, van der Graaf Y, Lampmann LE, Lohle PN, Juttmann JR. Pain response in the first trimester after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures with or without bone marrow edema. AJNR Am J Neuroradiol. 2006 Aug;27(7):1579-85. — View Citation

Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003. — View Citation

Wijn D and Mullen V. Biocompatibility of Acrylic lmplants. In Biocompatibility of Clinical lmplant Materials. Edited,CRC Press, 1981.

World Medical Association. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. 52nd WMA General Assembly, Edinburgh, Scotland, October 2000. Last amended with Note of Clarification of Paragraph 29 by the WMA General Assembly, Washington 2002 and Note of Clarification on Paragraph 30 by the WMA General assembly, Tokyo 2004.

* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	New fractures	Assess the effectiveness after administration of the investigational device compared to PMMA as measured by change of new fractures.	1 year
Primary	Location of fractures	Assess the location of new fractures: adjacent or non-adjacent to the treated vertebral or re-fractures of the treated vertebra after administration of the investigational device compared to PMMA.	1 year
Primary	Timing of fractures	Assess the timing of adjacent, non-adjacent and re-fractures of the treated vertebra after administration of the investigational device compared to PMMA.	1 year
Secondary	Pain measured by VAS	Assess the change in back pain at time points 5 days, 3 months, 12 months after administration of the investigational device compared to PMMA as measured by Visual Analogue Scale (VAS): scale 0-100, where 0 is no pain and 100 is the worst pain imaginable	12 months
Secondary	Function by ODI	Assess the change in function at time points 5 days, 3 months, 12 months after administration of the investigational device compared to PMMA as measured by Oswestry Disability Index (ODI): scale 0-100% where a higher score means a worse outcome	12 months
Secondary	Health related quality of life by SF-12	Assess the change in health related quality of life at time points 5 days, 3 months, 12 months after administration of the investigational device compared to PMMA as measured by SF-12: scale 0-100 where a higher score means a better outcome	12 months
Secondary	Safety measured by adverse events	Asses the safety of Inossia™ Cement Softener as measured by adverse events	12 months
Secondary	Hospital Beds	Record the number of hospital bed days (within hospital, nursing home, etc.) during the first week	1 week
Secondary	The vertebral height	The vertebral height at 12 months compared to baseline by X-ray (Average Mild Vertebral Body Height)	12 month
Secondary	Analgesic use	Record the analgesic use and compare to the WHO analgestic ladder	12 months
Secondary	Osteoporotic treatment regimen checklist	Record the osteoporotic treatment regimen	12 months