Fixation Using Alternative Implants for the Treatment of Hip Fractures (FAITH-2) (FAITH-2)

Fixation Using Alternative Implants for the Treatment of Hip Fractures (FAITH-2): A Multi-Centre 2x2 Factorial Randomized Trial Comparing Sliding Hip Screws Versus Cancellous Screws AND Vitamin D Versus Placebo on Patient Important Outcomes and Quality of Life in the Treatment of Young Adult (18-60) Femoral Neck Fractures

The purpose of this study is to determine the impact of surgical fixation (cancellous screws versus sliding hip screws) and biologic intervention (Vitamin D versus placebo) on patient important outcomes.

Study Overview

• Status: Terminated
• Conditions: Femoral Neck Fractures
• Intervention / Treatment: Drug: Vitamin D; Procedure: Sliding Hip Screw; Drug: Vitamin D Placebo; Procedure: Cancellous Screws

Detailed Description

Femoral neck fractures are a type of hip fracture associated with high complication rates and poor functional outcomes. It is estimated that over 300,000 hip fractures occur in patients under age 50 annually. Hip fractures in younger aged patients are particularly devastating with profound impairments of quality of life and function. Virtually all patients require surgical repair of their fractures and unlike elderly hip fractures, failure of surgery offers few options for salvage. Arthroplasty is a successful treatment for elderly patients; however, a hip replacement is not a viable option for younger patients because of their higher functional demands for work and recreational activities that are not tolerated by joint replacements.

There is more than one way to perform internal fixation for femoral neck fractures. Cancellous screws have traditionally been the preferred internal fixation implant for femoral neck fractures. Multiple screws (2 or more) are used during fixation, and advocates of this implant promote the construct's superior torsional stability, limited disruption of femoral head blood supply, minimally invasive insertion, and retention of more viable bone than the larger sliding hip screw (SHS). On the other hand, sliding hip screws have been gaining popularity and there is evidence to suggest that SHS provide greater fracture stability and may reduce patient complications. It is currently unknown which method of internal fixation provides the best outcomes for patients.

Femoral neck fracture treatment is further complicated by vitamin D insufficiency in as many as 8 of 10 trauma patients. Vitamin D plays an important role in musculoskeletal health and bone quality because it regulates serum calcium homeostasis. Laboratory research and human clinical studies suggest important associations between vitamin D, musculoskeletal health, and improved fracture healing. Experimental animal studies have demonstrated the concentration of vitamin D metabolites are higher at a fracture callus compared to the uninjured contralateral bone, vitamin D supplementation leads to decreased time to fracture union and increased callus vascularity, and vitamin D increases mechanical bone strength compared to controls. Clinical studies have also demonstrated that vitamin D supplementation increases the callus volume of proximal humerus fractures, increases the number and diameter of type II muscle fibres, and can improve wound healing, however, the effects of vitamin D supplementation in you patients with femoral neck fractures are unknown.

Using a 2x2 factorial design, participant will be randomly allocated to one of four treatment arms. Participants allocated to the cancellous screw group will receive multiple threaded screws (with a minimum of 3 screws and a minimum diameter of 6.5 mm) and those allocated to the sliding hip screw group will receive a single larger diameter partially threaded screw affixed to the proximal femur with a sideplate using a minimum of 2 screws for fixation. Participants allocated to the vitamin D Group will receive a bottle of 2,000 International Units (IU) vitamin D3 drops. Participants will be instructed to take two drops daily for six months, for a total daily dose of 4,000 IU. Participants in the placebo group will receive an identical bottle of placebo drops with no active ingredient. Similarly, they will be instructed to take two drops daily for six months. All vitamin D3 supplement and placebo bottles will be labeled in a blinded manner according to Health Canada and Good Manufacturing Practice.

Participation in this study will last 12 months. In-person participant follow-up visits will occur at enrollment (baseline), post-surgery, 6 weeks, 3 months, 6 months, 9 months, and 12 months post-surgery. Data for all outcomes and radiographs will be collected at each follow-up visit.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada
      • Royal Columbian Hospital
    • Vancouver, British Columbia, Canada
      • University of British Columbia & Vancouver Costal Health Authority
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre Winnipeg
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3X9
      • Memorial University
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • Ottawa, Ontario, Canada
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • The Center for Orthopedic Research and Education (CORE) Institute
  • California
    • San Francisco, California, United States, 94110
      • University of California, San Francisco
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University (IU Health Methodist Hospital)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare System
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny-Singer Research Institute
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Health Care Services
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Adult men or women ages 18 to 60 years.
2. Fracture of the femoral neck.
3. Fracture amenable to both surgical treatments (SHS and cancellous screws).
4. Operative treatment within 7 days of injury.
5. Provision of informed consent by patient or substitute decision maker.

Exclusion Criteria

1. Patients with previously diagnosed osteoporosis.
2. Fracture-dislocation of the femoral neck and hip joint.
3. Planned antegrade nailing of an ipsilateral femoral shaft fracture (if present).
4. Current infection around the hip (i.e. soft tissue or bone).
5. Stress fracture of the femoral neck.
6. Pathologic fractures secondary to neoplasm or other bone lesion.
7. Patients with known or likely undiagnosed disorders of bone metabolism such as Paget's disease, osteomalacia, osteopetrosis, osteogenesis imperfect, etc.
8. Patients with hyperhomocysteinemia.
9. Patient has an allergy to vitamin D or another contraindication to being prescribed vitamin D.
10. Patient is currently taking an over counter drug and/or food supplement that contains vitamin D and is unable or unwilling to discontinue its use for this study.
11. Likely problems, in the judgment of the attending surgeon, with maintaining follow up (e.g. patients with no fixed address, plans to move out of town). This may include patients with severe mental disorders and drug addictions without adequate support.
12. Pregnancy.
13. Patient is incarcerated.
14. Patient is not expected to survive injuries.
15. The attending surgeon believes the patient should be excluded because they are involved in a conflicting clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sliding Hip Screw and Vitamin D supplementation; Participants allocated to the vitamin D Group will be given a six-month supply of vitamin D3 supplementation. Participants in the vitamin D Group will receive a bottle of 2,000 International Units (IU) vitamin D3 drops (Ddrops®, Ddrops Company). Participants will be instructed to take two drops daily for six months, for a total daily dose of 4,000 IU.	Drug: Vitamin D; Procedure: Sliding Hip Screw
EXPERIMENTAL: Sliding Hip Screw and Vitamin D placebo; Participants in the placebo group will receive an identical bottle of placebo drops with no active ingredient. Similarly, they will be instructed to take two drops daily for six months. The placebo supplement is also manufactured by the Ddrops Company.	Procedure: Sliding Hip Screw; Drug: Vitamin D Placebo
EXPERIMENTAL: Cancellous Screws and Vitamin D supplementation; Participants allocated to the vitamin D Group will be given a six-month supply of vitamin D3 supplementation. Participants in the vitamin D Group will receive a bottle of 2,000 International Units (IU) vitamin D3 drops (Ddrops®, Ddrops Company). Participants will be instructed to take two drops daily for six months, for a total daily dose of 4,000 IU.	Drug: Vitamin D; Procedure: Cancellous Screws
EXPERIMENTAL: Cancellous Screws and Vitamin D placebo; Participants in the placebo group will receive an identical bottle of placebo drops with no active ingredient. Similarly, they will be instructed to take two drops daily for six months. The placebo supplement is also manufactured by the Ddrops Company.	Drug: Vitamin D Placebo; Procedure: Cancellous Screws

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Patient Important Outcomes	A participant met the primary clinical endpoint if they experienced one or more of the four outcomes: Re-operation: any unplanned surgery related to the treatment of the femoral neck fracture;; Femoral head osteonecrosis: any evidence of osteonecrosis on any follow-up medical imaging study (i.e., radiographs, magnetic resonance imaging (MRI), or other advanced imaging study);; Severe femoral neck malunion: fracture healing with femoral neck shortening of >10 mm in any plane on follow-up x-rays; or; Nonunion: failure of the fracture to progress towards healing defined as a Radiographic Union Score for Hip (RUSH) score below a pre-determined threshold specific for nonunion at 6 months or greater post-injury.	12 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-Operatively-Treated Fracture Healing Complications	Fracture healing complications treated non-operatively are presented in this table and included wound healing problems, infection (superficial and deep), hardware failure, hardware breakage, painful hardware, and peri-prosthetic fracture.	12 months post-surgery
Short Form-12 (SF-12) Physical Composite Scale (PCS)	The SF-12 is a 12-item questionnaire that measures self-reported quality of life through an 8-domain profile of functional health and well-being, physical and mental health summary measures and a preference-based health utility index. Scores range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.	Pre-fracture, 6 weeks, 3 months, 6 months, 9 months, 12 months post-surgery
Short Form-12 (SF-12) Mental Health Composite Scale (MCS)	The SF-12 is a 12-item questionnaire that measures self-reported quali... If reporting a score on a scale, please include the unabbreviated scale title, the minimum and maximum values, and whether higher scores mean a better or worse outcome. Scores range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.	Pre-fracture, 6 weeks, 3 months, 6 months, 9 months, 12 months post-surgery
Hip Outcome Score (HOS) Activities of Daily Living Scale	The HOS measures self-reported functional status through 28 items and two sub-scales that pertain to activities of daily living (ADLs) or higher level activities such as those necessary to participate in sports. Scores for each subscale range from 0 (least function) to 100 (most function).	Pre-fracture, 6 weeks, 3 months, 6 months, 9 months, 12 months post-surgery
Hip Outcome Score (HOS) Sports Scale	The HOS measures self-reported functional status through 28 items and two sub-scales that pertain to activities of daily living (ADLs) or higher level activities such as those necessary to participate in sports. Scores for each subscale range from 0 (least function) to 100 (most function).	Pre-fracture, 6 weeks, 3 months, 6 months, 9 months, 12 months post-surgery
Radiographic Fracture Healing	The date of healing will be determined by the Central Adjudication Committee (CAC). They will consider a fracture as healed when there is obliteration of the fracture line by newly formed bone along the cortices and within the trabecular bone on anterior-posterior and lateral radiographs.	up to 12 months post-surgery

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR); Hamilton Health Sciences Corporation; McMaster Surgical Associates
• Investigators: Principal Investigator: Gerard Slobogean, MD, University of Maryland, College Park; Study Director: Sheila Sprague, PhD, McMaster University (Role: Research Methodologist)

Publications and helpful links

General Publications

• Baitner AC, Maurer SG, Hickey DG, Jazrawi LM, Kummer FJ, Jamal J, Goldman S, Koval KJ. Vertical shear fractures of the femoral neck. A biomechanical study. Clin Orthop Relat Res. 1999 Oct;(367):300-5.
• Bee CR, Sheerin DV, Wuest TK, Fitzpatrick DC. Serum vitamin D levels in orthopaedic trauma patients living in the northwestern United States. J Orthop Trauma. 2013 May;27(5):e103-6. doi: 10.1097/BOT.0b013e31825cf8fb.
• Bhandari M, Devereaux PJ, Swiontkowski MF, Tornetta P 3rd, Obremskey W, Koval KJ, Nork S, Sprague S, Schemitsch EH, Guyatt GH. Internal fixation compared with arthroplasty for displaced fractures of the femoral neck. A meta-analysis. J Bone Joint Surg Am. 2003 Sep;85(9):1673-81. doi: 10.2106/00004623-200309000-00004.
• Bhandari M, Tornetta P 3rd, Hanson B, Swiontkowski MF. Optimal internal fixation for femoral neck fractures: multiple screws or sliding hip screws? J Orthop Trauma. 2009 Jul;23(6):403-7. doi: 10.1097/BOT.0b013e318176191f.
• Chen Z, Wang G, Lin J, Yang T, Fang Y, Liu L, Zhang H. [Efficacy comparison between dynamic hip screw combined with anti-rotation screw and cannulated screw in treating femoral neck fractures]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Jan;25(1):26-9. Chinese.
• Damany DS, Parker MJ, Chojnowski A. Complications after intracapsular hip fractures in young adults. A meta-analysis of 18 published studies involving 564 fractures. Injury. 2005 Jan;36(1):131-41. doi: 10.1016/j.injury.2004.05.023.
• Doetsch AM, Faber J, Lynnerup N, Watjen I, Bliddal H, Danneskiold-Samsoe B. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study. Calcif Tissue Int. 2004 Sep;75(3):183-8. doi: 10.1007/s00223-004-0167-0.
• Hamilton B. Vitamin D and human skeletal muscle. Scand J Med Sci Sports. 2010 Apr;20(2):182-90. doi: 10.1111/j.1600-0838.2009.01016.x. Epub 2009 Oct 5.
• Johansson A, Stromqvist B, Bauer G, Hansson LI, Pettersson H. Improved operations for femoral neck fracture. A radiographic evaluation. Acta Orthop Scand. 1986 Dec;57(6):505-9. doi: 10.3109/17453678609014779.
• Langlois K, Greene-Finestone L, Little J, Hidiroglou N, Whiting S. Vitamin D status of Canadians as measured in the 2007 to 2009 Canadian Health Measures Survey. Health Rep. 2010 Mar;21(1):47-55.
• Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K. Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruits. J Bone Miner Res. 2008 May;23(5):741-9. doi: 10.1359/jbmr.080102.
• Lidor C, Dekel S, Hallel T, Edelstein S. Levels of active metabolites of vitamin D3 in the callus of fracture repair in chicks. J Bone Joint Surg Br. 1987 Jan;69(1):132-6. doi: 10.1302/0301-620X.69B1.3029136.
• Linde F, Andersen E, Hvass I, Madsen F, Pallesen R. Avascular femoral head necrosis following fracture fixation. Injury. 1986 May;17(3):159-63. doi: 10.1016/0020-1383(86)90322-0.
• Lindequist S. Cortical screw support in femoral neck fractures. A radiographic analysis of 87 fractures with a new mensuration technique. Acta Orthop Scand. 1993 Jun;64(3):289-93. doi: 10.3109/17453679308993627.
• Malchau H, Herberts P, Eisler T, Garellick G, Soderman P. The Swedish Total Hip Replacement Register. J Bone Joint Surg Am. 2002;84-A Suppl 2:2-20. doi: 10.2106/00004623-200200002-00002. No abstract available. Erratum In: J Bone Joint Surg Am. 2004 Feb;86-A(2):363.
• Omeroglu H, Ates Y, Akkus O, Korkusuz F, Bicimoglu A, Akkas N. Biomechanical analysis of the effects of single high-dose vitamin D3 on fracture healing in a healthy rabbit model. Arch Orthop Trauma Surg. 1997;116(5):271-4. doi: 10.1007/BF00390051.
• Omeroglu S, Erdogan D, Omeroglu H. Effects of single high-dose vitamin D3 on fracture healing. An ultrastructural study in healthy guinea pigs. Arch Orthop Trauma Surg. 1997;116(1-2):37-40.
• Patil S, Garbuz DS, Greidanus NV, Masri BA, Duncan CP. Quality of life outcomes in revision vs primary total hip arthroplasty: a prospective cohort study. J Arthroplasty. 2008 Jun;23(4):550-3. doi: 10.1016/j.arth.2007.04.035. Epub 2007 Oct 23.
• Sakalli H, Arslan D, Yucel AE. The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatol Int. 2012 Aug;32(8):2279-83. doi: 10.1007/s00296-011-1943-6. Epub 2011 May 10.
• Swiontkowski MF, Harrington RM, Keller TS, Van Patten PK. Torsion and bending analysis of internal fixation techniques for femoral neck fractures: the role of implant design and bone density. J Orthop Res. 1987;5(3):433-44. doi: 10.1002/jor.1100050316.
• FAITH-2 Investigators; Slobogean GP, Sprague S, Bzovsky S, Heels-Ansdell D, Thabane L, Scott T, Bhandari M. Fixation using alternative implants for the treatment of hip fractures (FAITH-2): design and rationale for a pilot multi-centre 2 x 2 factorial randomized controlled trial in young femoral neck fracture patients. Pilot Feasibility Stud. 2019 May 28;5:70. doi: 10.1186/s40814-019-0458-x. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (ACTUAL): March 18, 2019
• Study Completion (ACTUAL): March 18, 2019

Study Registration Dates

• First Submitted: July 18, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (ESTIMATE): July 26, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Femoral Neck Fractures; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: FAITH-2