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

• ClinicalTrials.gov Identifier: NCT03453905
• Recruitment Status: Unknown
• First Posted: March 5, 2018
• Last Update Posted: March 5, 2018
• Sponsor: Tel-Aviv Sourasky Medical Center
• Information provided by (Responsible Party): Tel-Aviv Sourasky Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bone Neoplasm of Hip (Diagnosis); Orthopedic Disorder; Bone Metastases; Proximal Femoral Metaphyseal Abnormality	Diagnostic Test: CTFEA; Other: Conventional decision algorithm	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized to two arms and followed prospectively
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Evaluation of the Ability of CT-based Finite Element Analysis (CTFEA) to Predict Fractures in Patients With Metastases: a Randomized Controlled Study.
• Estimated Study Start Date: March 1, 2018
• Estimated Primary Completion Date: March 1, 2022
• Estimated Study Completion Date: March 1, 2022

Arms and Interventions

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 Name: CT-based Finite Element Analysis
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 Name: Conventional

Outcome Measures

Primary Outcome Measures :

1. Primary efficacy hypothesis [ Time Frame: four years ]
   To compare proportion of patients undergoing surgery in the treatment group vs the control group.

Secondary Outcome Measures :

1. Composite endpoint [ Time Frame: 4 months ]
   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

Other Outcome Measures:

1. All-cause mortality [ Time Frame: 4 years ]
   All-cause mortality
2. Number of patients who became unable to ambulate [ Time Frame: 4 years ]
   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.
3. Number of participants who sustained a pathological fracture [ Time Frame: 4 months ]
   Number of participants who sustained a pathological fracture. Diagnosis of pathological fracture will be determined by an orthopedic surgeon based on imaging.
4. Death [ Time Frame: 30 days ]
   Death within 30 days after prophylactic surgery
5. Surgical complications [ Time Frame: 4 months ]
   Infection, re-operation, mechanical failure within 4 months of follow up
6. Number of surgeries avoided [ Time Frame: 4 months ]
   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.
7. Agreement of two measures of fracture risk [ Time Frame: One week ]
   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
8. Patients who denied surgery [ Time Frame: 4 months ]
   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.
9. Complications that could be prevented by CTFEA [ Time Frame: One month ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Haggai Schermann, MD; 0528771014 ext +972; sheralmi@bu.edu

Contact: Amir Sternheim, MD; amirst@tlvmc.gov.il

Sponsors and Collaborators

Tel-Aviv Sourasky Medical Center

Investigators

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

More Information

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. Review.

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. 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.

• Responsible Party: Tel-Aviv Sourasky Medical Center
• ClinicalTrials.gov Identifier: NCT03453905
• Other Study ID Numbers: 0532-17-TLV
• First Posted: March 5, 2018
• Last Update Posted: March 5, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: The individual participant data will remain in TLVMC and will not be shared

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tel-Aviv Sourasky Medical Center:

CT-based Finite Element Analysis; Randomized Controlled Study; Preventive bone fixation; Randomized Controlled Trial

Additional relevant MeSH terms:

Neoplasm Metastasis; Bone Neoplasms; Musculoskeletal Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Neoplasms by Site; Bone Diseases