Evaluation of the Ability of CT-based Finite Element Analysis (CTFEA) to Predict Fractures in Patients With Metastases: a Randomized Controlled Study. (ZYCTFEA)

Patients with metastases to proximal femur, who are evaluated fr the risk of pathologic fracture in order to decide on preventive fixation vs follow-up constitute the study population. The patients will be randomized in two arms. First arm - the decision of treatment will rely on conventional decision algorithm including specialist judgement and Mirels' score. Second arm- the decision on treatment will be supported by CTFEA analysis of bone structure and quantitative simulation-based estimate of fracture risk, in addition to the conventional decision algorithm. Operation rates, pathologic fracture rates and additional secondary outcomes will be compared between the two study arms.

Study Overview

• Status: Unknown
• Conditions: Bone Metastases; Orthopedic Disorder; Bone Neoplasm of Hip (Diagnosis); Proximal Femoral Metaphyseal Abnormality
• Intervention / Treatment: Diagnostic test: CTFEA; Other: Conventional decision algorithm

• Study Type: Interventional
• Enrollment (Anticipated): 162
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Haggai Schermann, MD; Phone Number: +972 0528771014; Email: sheralmi@bu.edu
• Study Contact Backup: Name: Amir Sternheim, MD; Email: amirst@tlvmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Metastatic bone disease of femur
2. Patients who undergo a CT scan (soft tissue kernel/filter, 120 kVp), and have at least 2/3 of both femurs visible in the CT scan. If CT scan is performed at the Sourasky medical center it must be according to the protocol in Appendix A.

Exclusion Criteria:

1. Ipsilateral previous surgery with or without implants
2. Low quality CT scan or CT does not include at least 2/3 of the femurs.
3. History of fractures, radiation or surgeries in lower limbs.
4. Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTFEA; Decision on preventive surgery vs follow-up will be based on expert judgement, Mirels' score and CTFEA	Diagnostic test: CTFEA; CT scans are used to generate a finite element model of patient-specific long bones. The bone model is loaded in stance position. Load based on patient's weight and the mechanical response, including the risk of fracture, is computed.; Other Names: CT-based Finite Element Analysis
Other: Mirels; Decision on preventive surgery vs follow-up will be based on expert judgement and Mirels' score	Other: Conventional decision algorithm; Decision on surgery vs follow-up will be based on expert opinion and Mirels' score; Other Names: Conventional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy hypothesis	To compare proportion of patients undergoing surgery in the treatment group vs the control group.	four years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint	pathological fracture during 4 months of follow up OR death within 30 days after prophylactic surgery in patients who underwent surgery OR surgical complications within 4 months of follow up: infection, re-operation, mechanical failure	4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality	4 years
Number of patients who became unable to ambulate	Number of patients who became unable to ambulate for any reason. Inability to ambulate will be determined by an orthopedic surgeon from anamnesis and physical examination.	4 years
Number of participants who sustained a pathological fracture	Number of participants who sustained a pathological fracture. Diagnosis of pathological fracture will be determined by an orthopedic surgeon based on imaging.	4 months
Death	Death within 30 days after prophylactic surgery	30 days
Surgical complications	Infection, re-operation, mechanical failure within 4 months of follow up	4 months
Number of surgeries avoided	The number of surgeries "avoided" - presented only in the group of Intervention and only in patients without the safety endpoint within 4 months of follow up. Specifically, number of patients without the safety endpoint in whom a physician changed his/her decision to operate based on the CT-based FE analysis.	4 months
Agreement of two measures of fracture risk	Agreement between the pathological fracture risk estimated using Mirels' scale and the pathological fracture risk CT-based FE simulation analysis. Risk levels determined by either of the estimates: low, medium, high	One week
Patients who denied surgery	Number of patients who did not undergo a prophylactic surgery, in whom the CT-based FE analysis showed a risk above moderate for fractures in future and who developed a fracture during the 4 months of follow-up - calculated in both study groups.	4 months
Complications that could be prevented by CTFEA	Number of patients who underwent a prophylactic surgery, in whom the CT-based FE analysis showed a mild-moderate risk of a fracture and who devel-oped a complication (as defined in a composite safety endpoint) - calculated in both study groups	One month

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Investigators: Principal Investigator: Amir Sternheim, MD, Tel-Aviv Sourasky Medical Center

Publications and helpful links

General Publications

• Bickels J, Dadia S, Lidar Z. Surgical management of metastatic bone disease. J Bone Joint Surg Am. 2009 Jun;91(6):1503-16. doi: 10.2106/JBJS.H.00175.
• Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989 Dec;(249):256-64.
• Goodheart JR, Cleary RJ, Damron TA, Mann KA. Simulating activities of daily living with finite element analysis improves fracture prediction for patients with metastatic femoral lesions. J Orthop Res. 2015 Aug;33(8):1226-34. doi: 10.1002/jor.22887. Epub 2015 May 21.
• Yosibash Z, Trabelsi N, Milgrom C. Reliable simulations of the human proximal femur by high-order finite element analysis validated by experimental observations. J Biomech. 2007;40(16):3688-99. doi: 10.1016/j.jbiomech.2007.06.017. Epub 2007 Aug 13.
• Trabelsi N, Yosibash Z, Wutte C, Augat P, Eberle S. Patient-specific finite element analysis of the human femur--a double-blinded biomechanical validation. J Biomech. 2011 Jun 3;44(9):1666-72. doi: 10.1016/j.jbiomech.2011.03.024. Epub 2011 Apr 15. Erratum In: J Biomech. 2012 Feb 23;45(4):724-5.
• Yosibash Z, Plitman Mayo R, Dahan G, Trabelsi N, Amir G, Milgrom C. Predicting the stiffness and strength of human femurs with real metastatic tumors. Bone. 2014 Dec;69:180-90. doi: 10.1016/j.bone.2014.09.022. Epub 2014 Oct 2.
• Benca E, Patsch JM, Mayr W, Pahr DH, Windhager R. The insufficiencies of risk analysis of impending pathological fractures in patients with femoral metastases: A literature review. Bone Rep. 2016 Mar 2;5:51-56. doi: 10.1016/j.bonr.2016.02.003. eCollection 2016 Dec.
• Nazarian A, Entezari V, Zurakowski D, Calderon N, Hipp JA, Villa-Camacho JC, Lin PP, Cheung FH, Aboulafia AJ, Turcotte R, Anderson ME, Gebhardt MC, Cheng EY, Terek RM, Yaszemski M, Damron TA, Snyder BD. Treatment Planning and Fracture Prediction in Patients with Skeletal Metastasis with CT-Based Rigidity Analysis. Clin Cancer Res. 2015 Jun 1;21(11):2514-9. doi: 10.1158/1078-0432.CCR-14-2668. Epub 2015 Feb 27.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2018
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: February 15, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): March 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; CT-based Finite Element Analysis; Randomized Controlled Study; Preventive bone fixation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Neoplastic Processes; Bone Diseases; Neoplasm Metastasis; Bone Neoplasms; Musculoskeletal Diseases
• Other Study ID Numbers: 0532-17-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The individual participant data will remain in TLVMC and will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No