Randomized Clinical Trial Evaluating Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures
Phase: NA
Conditions: Medial Malleolus Fractures
Sponsor: Stanford University

 
 
 
 
 
Randomized Clinical Trial Evaluating Acutrak Headless Compression 
Screw Fixation of Medial Malleolus Fractures 
Study Protocol and Statistical Analysis Plan 
NCT03061279 
 October 26, 2016 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
Amanatullah 
 
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Randomized Clinical Trail Evaluating Acutrak Headless Compression Screw Fixation 
of Medial Malleolus Fractures 
 
 
 
 
Derek F. Amanatullah, M.D., Ph.D. (Principal Investigator) 
Julius A. Bishop, M.D. (Co-Investigator) * 
Domingo A. Hallare, M.D. (Co-Investigator) ‡ 
Micheal J Weaver M.D (Co-Investigator) # 
 
*Department of Orthopaedic Surgery 
Stanford Hospital and Clinics 
Palo Alto, CA 
 
‡Department of Orthopaedic Surgery 
Kaiser Permanente 
Sacramento, CA 
 
#  Department of Orthopaedic Surgery 
   Brigham and Women's Hospital, Boston, MA 02115 
 
 
 
 
 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
Amanatullah 
 
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INTRODUCTION 
Medial malleolus fractures can arise from the application of axial force at various 
anatomical positions of the ankle. Supination-external rotation, pronation-external 
rotation, or pronation-abduction results in an oblique fracture pattern. Supination-
adduction results in a vertical shear fracture pattern. Multiple techniques have been 
described for fixation of the medial malleolus.1,2 The AO group currently advocates two 
parallel 4.0 mm partially threaded cancellous screws oriented perpendicular to the 
fracture line to provide compression as the gold standard for medial malleolus fixation. 
Static load to failure testing our laboratory has challenged this observation in 
horizontal medial malleolus fracture patterns.3,4 We previously demonstrated superior 
stiffness (178 ± 26 N/mm) and load at 2 mm of ankle joint displacement (362 ± 72 N) with 
a contoured mini-fragment T-plate fixation versus two parallel 4.0 mm cancellous screw 
fixation (141 ± 24 N/mm and 292 ± 47 N, respectively) and tension band wire fixation (124 
± 16 N/mm and 267 ± 43 N, respectively) of horizontal medial malleolus fractures (p < 
0.05).3 We recently demonstrated (manuscript submitted) contoured mini-fragment T-
plate fixation is biomechanically equivalent to bicortical screw fixation with respect to 
construct stiffness (684 ± 101 N/mm and 668 ± 61 N/mm, respectively) and load at 2 mm 
of ankle joint displacement (239 ± 83 N and 240 ± 17 N, respectively) in static load to 
failure testing of horizontal medial malleolus fractures. However, both constructs were 
superior to unicortical screw fixation (392 ± 34 N/mm and 102 ± 20 N, respectively) of 
horizontal medial malleolus fractures (p < 0.05). 
Static load to failure testing our laboratory has challenged this observation in 
vertical medial malleolus fracture patterns as well.5-7 We recently demonstrated 
(manuscript submitted) superior stiffness (463 ± 91 N/mm) and load at 2 mm of ankle joint 
displacement (922 ± 297 N) with antiglide plate fixation versus unicortical screw fixation 
(111 ± 35 N/mm and 284 ± 51 N, respectively) and bicortical screw fixation (279 ± 30 
N/mm and 429 ± 112 N, respectively) of vertical medial malleolus fractures (p < 0.05). 
Superior fixation requires extensive dissection and fixation known to result in 
prominent hardware and hardware related pain. None of these fixation methods address 
the lack of soft tissue to cover the medial malleolus and the common practice of hardware 
removal to address post-fixation hardware pain. Retrospective review of ankle hardware 
removal cases indicates that 6% (8/126) of patients have their hardware removed for non-
pain issues (e.g., infection, etc.) at 6 months and 17% (22/126) of patients have their 
hardware removed for pain on the medial 
or lateral side of the ankle at 6 months.8 
The headless configuration of the 
Acutrak system makes it ideal for medial 
malleolus fixation and may obviate the 
need for hardware removal. We recently 
demonstrated 
(manuscript 
submitted) 
superior stiffness and load at 2 mm of 
ankle joint displacement of an Acutrak 
screw construct (244 ± 58 N/mm and 483 
± 91 N, respectively) when compared to 
partially 
threaded 
parallel 
unicortical 
cancellous screw construct (111 ± 35 N/mm and 278 ± 49 N, respectively) in static load 
 
 
 
 
Figure 1: Vertical shear medial malleolus fractures 
fixed with cancellous screws (left) and Acutrak 
screws (right) demonstrating the lack of hardware 
prominence after fixation as well as maintenance of 
reduction after off-set axial loading. 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
Amanatullah 
 
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to failure testing of vertical medial malleolus fractures. Additionally, when the specimens 
were displaced to 6 mm and allowed to relax, the Acutrak headless compression screw 
constructs reduced to the pretesting fragment alignment while the parallel cancellous 
constructs remained displaced (see Figure 1). 
 
HYPOTHESIS 
The fixation provided by the Acutrak headless compression screws provide 
sufficient fixation to achieve union and a favorable clinical outcome in both horizontal and 
vertical medial malleolus fractures when compared to bicortical and unicortical screw 
fixation, tension band wiring, and mini-fragment or buttress plating. However, minimizing 
the amount of dissection required for implantation as well as lack of prominent hardware 
surfaces will reduce the incidence and severity of hardware related pain and 
correspondingly the necessity of hardware removal. 
 
Specific Aims 
1) Prospectively establish equivalence with respect to fracture union rate after Acutrak 
headless compression screw fixation when compared to other fixation methods for 
medial malleolus fractures. 
2) Prospectively establish equivalence with respect Patient Reported Outcome 
Measurement Information System (PROMIS) scores after Acutrak headless 
compression screw fixation when compared to other fixation methods for medial 
malleolus fractures. 
3) Prospectively establish superiority with respect to hardware related pain after Acutrak 
headless compression screw fixation when compared to other fixation methods for 
medial malleolus fractures. 
4) Prospectively establish superiority with respect to the hardware removal rate after 
Acutrak headless compression screw fixation when compared to other fixation 
methods for medial malleolus fractures. 
 
Study Design 
 
Institutional Review Board and HIPAA 
The institutional review boards of Stanford Hospital and Clinics and the Kaiser 
Permanente Hospital, South Sacramento will review and approve this study prior to 
initiation. All patient information will be kept confidential in accordance with HIPAA and 
only the study coordinator and the protocol director will have access to the data. 
 
Inclusion/Exclusion Criteria 
All ankle fractures that undergo open reduction internal fixation of the medial malleolus 
in adults at or over 18 years-of-age will be considered for inclusion.  
We will specifically exclude pediatric ankle fractures in children under 18 years-of-age, 
tibial plafond (pilon) fractures in children and adults, medial malleolar osteotomies to 
access the talus, perform an ankle fusion, or deal with a pathologic lesion, osteonecrosis, 
or infection due to their diversity in diagnosis, management, and weight bearing status. 
Patients with prior surgical treatment of the ankle for fracture, deformity, infection, 
neoplasia, or other pathologic process on the ipsilateral extremity will also be excluded. 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
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Patients that are non-weight bearing on one or both lower extremities prior to sustaining 
their ankle injury will be excluded. 
 
Randomization 
All elective and emergent admissions to Stanford Hospital and Clinics and Kaiser 
Permanente – South Sacramento that meet our inclusion/exclusion criteria will be 
identified and solicited for consent. Patients will be randomized by sealed envelope to 
surgical fixation with traditional headed screws, plates, and wires or Acutrak headless 
compression screws. At the time of randomization, the fracture pattern and severity, past 
medical history and medications, and demographic data will be documented. 
 
Follow-up Protocol 
After operative fixation, patients will receive fracture follow-up with a clinical evaluation 
for tenderness, radiographs to evaluate stability and union at 2 weeks, 6 weeks, 3 months 
of surgery and complete the PROMIS and VAS pain scores. Patients will be followed by 
telephonically once the fracture union is confirmed radiologically by the operating surgeon 
at 6 months, 1 year, and 2 years after surgical fixation. The VAS pain scores will be 
administered telephonically and the PROMIS questionnaires will be mailed to the patients 
(Table 1).9 
 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
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Table 1: Protocol Summary 
Time and Event Table 
Injury/Office 2 weeks 
6 weeks 
3 
month
s 
6 months 
(over 
Telephone & 
mail) 
1 year 
(over 
Telephone
& mail) 
2 years 
(over 
Telephone
& mail) 
Discuss Study  
X 
 
 
 
 
 
 
Screening Log 
X 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
Eligibility Worksheet 
X 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
Clinical Assessment 
• Medial Ankle Tenderness 
• Lateral Ankle Tenderness 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Patient Reported Outcomes 
• PROMIS Score  
• VAS Pain (by location) 
• On Narcotics (yes/no) 
 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X  
X 
X 
 
X 
X 
X 
 
X 
X 
X 
Radiographs 
• Anterior-to-Posterior Ankle 
• Lateral Ankle 
X 
X 
X 
X 
X 
X 
X 
X 
- 
           - 
- 
- 
- 
- 
Operative/Device 
X 
 
 
 
 
 
 
Removal of Hardware 
 
X 
X 
X 
X 
X 
X 
Adverse Event 
X 
X 
X 
X 
X 
X 
X 
End of Study 
 
 
 
 
 
 
X 
 
Criteria for Removal of Hardware 
 
Hardware may be removed if there is a surgical indication or patient/surgeon 
preference for removal. Patients will be asked whether they feel bothersome sensitivity 
at the both medial and lateral malleolus. If they mention sensitivity to light touch that is 
not bothersome they should not be subjected to hardware removal unless by patient or 
surgeon preference and noted as medial or lateral hardware removed for preference. 
On the other hand, if they mention bothersome sensitivity, it would be rated on a 0-5 
Likert intensity scale. All bothersome sensation will be subjected to hardware removal 
and noted as removal for sensitivity. Other reasons for hardware removal 
indications include infection and non-union or mal-union requiring revision open 
reduction and internal fixation. The location of symptoms and reason for hardware 
removal should be specified and documented. 
 
Documentation of Fracture Union 
Union will be defined as a pain free facture site on examination with evidence of 
radiographic healing and a return to full weight bearing confirmed by the operating 
surgeon 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
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Power Analysis and Statistics 
Retrospective review of ankle hardware removal cases indicates that 6% (8/126) 
of patients have their hardware removed for non-pain issues (e.g., infection, etc.) at 6 
months and 17% (22/126) of patients have their hardware removed for pain on the medial 
or lateral side of the ankle at 6 months.8 Hence, the overall rate of hardware removal is 
24% but if we can reduce half of the medial hardware removals the overall rate would be 
14.5%. To detect this 9.5% difference, it would take 424 randomized patients (alpha = 
0.05, and 80% power). Medial hardware removal will be prohibited for lateral hardware 
pain. 
Utilizing the STRIDE database available at Stanford University, there have been 
155 procedures involving fixation of the medial malleolus (CPT: 27766, 27814, 27822, 
27823) over the past three years. Assuming a similar procedure burden at the other major 
Level I Trauma center and extrapolating this three-year data, we estimate the capability 
to enroll 500 patients over three years. 
All continuous variables will be reported as the mean and errors are reported as 
standard deviation. All categorical variables will be reported as the subset number and 
percentage of the total. Comparisons will be performed with the appropriate statistical test 
when indicated. Statistical significance will be set at p less than 0.05 with an appropriate 
Bonferroni correction for multiple comparisons when indicated. 
 
Budget 
 
The vast majority of the budget will go toward an experienced fulltime clinical 
research coordinator, level II (CRCII, Table 2). This person is critical to our success. 
Appropriately, some funds will be devoted to insuring the proper training and certification 
for the CRCII involved in this project as well as supply adequate computing power and 
meet secure data storage needs. Some funds would be used by the principal investigator 
and co-investigators to offset local travel and travel to national and international meetings 
to present the findings of this interdisciplinary work, including the American Academy of 
Orthopaedic Surgeons (AAOS), the Orthopaedic Trauma Association (OTA), and the 
American Orthopaedic Foot and Ankle Society (AOFAS). 
 
 
 
 
Table 2: General Budget 
 
Expense 
 
 
Effort Cost 
Personnel 
Principal Investigator Derek F. Amanatullah 
10% 
$36,000/year 
 
Co-Investigator 
Kenneth J. Hunt 
3% 
$10,000/year 
 
Co-Investigator 
Julius A. Bishop 
3% 
$10,000/year 
 
Co-Investigator 
Chris D. Kreulen 
3% 
$10,000/year 
 
Co-Investigator 
Philip R. Wolinsky 
3% 
$10,000/year 
 
Co-Investigator 
Domingo Hillare 
3% 
$10,000/year 
 
CRCII 
TBD: Stanford 
100% $90,000/year 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
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CRCII 
TBD: 3rd center 
75% 
$68,000/year 
 
CRCII 
TBD: Kaiser 
75% 
$68,000/year 
 
 
 
 
 
Equipment 
Computers 
 
 
$3,000/year 
 
Secure Storage 
 
 
$1,000/year 
 
 
 
 
 
Training 
 
 
 
$5,000/year 
 
 
 
 
 
Travel 
Society Meetings 
 
 
$5,000/year 
 
Between Sites 
 
 
$5,000/year 
 
 
 
 
$275,000/year 
 
 
 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
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Acumed Study Summary 
Company  
Stanford University 
Title 
Prospective, multi-center, randomized, controlled study evaluating the union 
rate, rate of medial malleolus hardware removal and clinical outcomes after 
medial malleolus fracture fixation with Acutrak headless compression screws 
Short Title 
Acutrak Fixation of Medial Malleolus Fractures 
Protocol Number 
 
Treatment Device 
Acutrak headless compression screws 
Control Device(s) 
Mini-fragment Plating, Antiglide Plating, Headed Unicortical Screws, Headed 
Bicortical Screws, Tension Band Wiring 
Intended Use 
The Acutrak headless compression screws are intended to provide fixation and 
anatomically reduce fractures of the medial malleolus that occur via supination-
external rotation, pronation-external rotation, or pronation-abduction resulting in 
an oblique fracture pattern as well as supination-adduction resulting in a vertical 
shear fracture pattern. 
Study Purpose 
The fixation provided by the Acutrak headless compression screws provide 
sufficient fixation to achieve union and a favorable clinical outcome in both 
horizontal and vertical medial malleolus fractures when compared to bicortical 
and unicortical screw fixation, tension band wiring, and mini-fragment or 
buttress plating. However, minimizing the amount of dissection required for 
implantation as well as lack of prominent hardware surfaces will reduce the 
incidence and severity of hardware related pain and correspondingly the 
necessity of hardware removal. 
Study Objectives 
Primary:  
• A successful outcome would be a reduction in the rate or severity of 
hardware related pain localized to the medial malleolus reducing the 
incidence of hardware removal from the medial malleolus at one year after 
sustaining an ankle fracture. 
Secondary:   
• Another successful outcome would be an equivalent radiographic and 
clinical union rate when compared to traditional fixation methods. 
• Another successful outcome would be an equivalent PROMIS scores when 
compared to traditional fixation methods. 
Safety Objective: 
• Prospectively establish equivalence with respect to fracture union rate 
after Acutrak headless compression screw fixation when compared to 
other fixation methods for medial malleolus fractures. 
• Prospectively establish equivalence with respect to Patient Reported 
Outcome Measurement Information System (PROMIS) scores  after 
Acutrak headless compression screw fixation when compared to other 
fixation methods for medial malleolus fractures. 
• Prospectively establish superiority with respect to hardware related pain 
after Acutrak headless compression screw fixation when compared to 
other fixation methods for medial malleolus fractures. 
• Prospectively establish superiority with respect to the hardware removal 
rate after Acutrak headless compression screw fixation when compared 
to other fixation methods for medial malleolus fractures. 
 

Acutrak Headless Compression Screw Fixation of Medial Malleolus Fractures 
 
 
 
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Evaluation Tools 
Subjective: VAS Pain Score, Fracture Union 
Objective: Complications, PROMIS Scores 
Subject Population 
Patients sustaining a horizontal or vertical medial malleolus facture as a result 
of supination-external rotation, pronation-external rotation, pronation-
abduction, or supination-adduction of the ankle resulting in a fracture. 
Critical Eligibility 
Criteria 
Inclusion:   
All ankle fractures that undergo open reduction internal fixation of the medial 
malleolus in adults at or over 18 years-of-age will be considered for inclusion.  
Exclusion: 
• pediatric ankle fractures 
• tibial plafond (pilon) fractures in children and adults 
• medial malleolar osteotomies to access the talus, perform an ankle 
fusion, or deal with a pathologic lesion, osteonecrosis, or infection 
• prior surgical treatment of the ankle for fracture, deformity, infection, 
neoplasia, or other pathologic process 
• non-weight bearing on one or both lower extremities prior to sustaining 
their ankle injury 
Definition of Enrollment 
Meeting Inclusion/Exclusion Criteria and Signed Informed Consent 
Number of Subjects 
Utilizing the STRIDE database available at Stanford University, there have 
been 155 procedures involving fixation of the medial malleolus (CPT: 27766, 
27814, 27822, 27823) over the past three years. Assuming a similar 
procedure burden at another major Level I Trauma center at Kaiser 
Permanente Hospital, South Sacramento and extrapolating this three-year 
data, we estimate the capability to enroll and randomize over 500 patients 
requiring medial malleolus fixation over three years between the three centers. 
Number of Sites 
Three Level I Trauma Centers will participate: 
• 
Stanford Hospital and Clinics 
• 
Kaiser Permanente – South Sacramento 
• 
Brigham and Women's Hospital- Boston 
Procedure Schedule 
See Table 1 
Subject Duration   
The estimated duration for each subject is 2 years. Subjects are released from 
postoperative follow-up after post-operative observation for two years. 
Study Duration 
The estimated duration of the study is 5 years: 3 years for enrollment and 2 
year for postoperative follow-up for each enrolled subject. 
Safety 
All adverse events and complications will be continuously monitored 
throughout the study.  The type and frequency will be analyzed by a medical 
monitor.  
Statistical Methods 
All continuous variables will be reported as the mean and errors are reported as 
standard deviation. All categorical variables will be reported as the subset 
number and percentage of the total. Comparisons will be performed with the 
appropriate statistical test when indicated. Statistical significance will be set at 
p less than 0.05 with an appropriate Bonferroni correction for multiple 
comparisons when indicated. 

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References 
1. 
Rovinsky D, Haskell A, Liu Q, Paiement GD, Robinovitch S. Evaluation of a new method of small 
fragment fixation in a medial malleolus fracture model. Journal of orthopaedic trauma. 
2000;14(6):420-425. 
2. 
Toolan BC, Koval KJ, Kummer FJ, Sanders R, Zuckerman JD. Vertical shear fractures of the medial 
malleolus: a biomechanical study of five internal fixation techniques. Foot & ankle international. 
1994;15(9):483-489. 
3. 
Amanatullah DF, McDonald E, Shellito A, et al. Effect of mini-fragment fixation on the 
stabilization of medial malleolus fractures. The journal of trauma and acute care surgery. 
2012;72(4):948-953. 
4. 
Amanatullah DF, Wolinsky PR. An alternative fixation technique for small medial malleolus 
fractures. Orthopedics. 2010;33(12):888-889. 
5. 
Dumigan RM, Bronson DG, Early JS. Analysis of fixation methods for vertical shear fractures of 
the medial malleolus. Journal of orthopaedic trauma. 2006;20(10):687-691. 
6. 
Fowler TT, Pugh KJ, Litsky AS, Taylor BC, French BG. Medial malleolar fractures: a biomechanical 
study of fixation techniques. Orthopedics. 2011;34(8):e349-355. 
7. 
Amanatullah DF, Khan SN, Curtiss S, Wolinsky PR. Effect of divergent screw fixation in vertical 
medial malleolus fractures. The journal of trauma and acute care surgery. 2012;72(3):751-754. 
8. 
Brown OL, Dirschl DR, Obremskey WT. Incidence of hardware-related pain and its effect on 
functional outcomes after open reduction and internal fixation of ankle fractures. Journal of 
orthopaedic trauma. 2001;15(4):271-274. 
9. 
Hung M, Baumhauer JF, Latt LD, et al. Validation of PROMIS (R) Physical Function computerized 
adaptive tests for orthopaedic foot and ankle outcome research. Clinical orthopaedics and 
related research. 2013;471(11):3466-3474.