Delayed Loading Following Repair of a Ruptured Achilles Tendon - a Randomized Controlled Trial
Phase: NA
Conditions: Achilles Tendon Rupture
Sponsor: Bispebjerg Hospital

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STATISTICAL ANALYSIS PLAN 
 
Delayed loading following repair of ruptured Achilles tendon  
– A randomized controlled trial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Index: 
INDEX: ...................................................................................................................................................................... 2 
BACKGROUND .......................................................................................................................................................... 3 
Purpose ..................................................................................................................................................................... 3 
Hypotheses ................................................................................................................................................................ 3 
STUDY DESIGN .......................................................................................................................................................... 3 
Participants ............................................................................................................................................................... 4 
Blinding ..................................................................................................................................................................... 4 
Sample size calculation ............................................................................................................................................. 5 
OUTCOME ASSESSMENTS ......................................................................................................................................... 5 
Primary outcome ....................................................................................................................................................... 5 
Secondary outcomes ................................................................................................................................................. 5 
POPULATION TO BE ANALYZED ................................................................................................................................. 5 
Intension-to-treat (ITT) .............................................................................................................................................. 6 
Per protocol (PP) ....................................................................................................................................................... 6 
ANALYSIS .................................................................................................................................................................. 6 
Primary outcome ....................................................................................................................................................... 7 
Secondary outcome ................................................................................................................................................... 7 
Table of the analysis .................................................................................................................................................. 7 
REFERENCES ............................................................................................................................................................. 8 
 
 
 
 
 
 
 
 
 
 

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Background 
Leisure time physical activity is unquestionably associated with numerous health benefits. 
However, some of these recreational activities are also accompanied with some increased risk of 
injury. For example, there appears to be an increased risk of Achilles tendon ruptures with some 
recreational sports (1). Specifically, this increased incidence can be seen in high-impact sports, 
including badminton, volleyball, and soccer (2, 3). Acute Achilles tendon ruptures occurs in both 
men and women but is most frequent in men 30-50 years of age that participate in recreational 
sports periodically (1, 4, 5). The prevalence is reported to be ~ 18 per 100,000 per year, and the 
incidence appear to be on the rise (1, 4-6). Yet, evidenced based knowledge of how to best 
rehabilitate the injury after repair of the rupture is largely absent in the literature, which likely 
contributes to the reports of persistent muscle weakness, tendon elongation and incomplete 
return to pre-injury level (7-18). It has been suggested that preventing tendon elongation during 
rehabilitation improves the clinical outcome, which is the very aim of this project. 
 
Purpose  
The purpose of the present study is to investigate if delayed loading following surgical treated 
Achilles tendon rupture influence the clinical outcome and muscle and tendon structure after one 
year.  
 
Hypotheses  
We hypothesize that delaying the gradual introduction of loading in the initial 26 weeks may 
reduce the heel-rise deficit (primary outcome) and thus improve the clinical outcome one year 
after surgery (primary endpoint). 
 
Study design 
This study is a single-blinded prospective randomized controlled superiority trial with 2 parallel 
arms. (The study will be registered by ClinicalTrials.gov). We will examine if delaying initiation of 
loading in the initial 26 weeks will influence the tendon healing and elongation compared to 
current accepted clinical guidelines for rehabilitation (‘accelerated rehabilitation’) of surgically 
repaired Achilles tendon ruptures. One arm will include current clinical practice that calls for 
partial weight bearing from week 3, full weight bearing from week 7, and total bracing time 6 

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weeks. The other arm will not be allowed partial weight bearing with the use of crutches until 
week 7 and full weight bearing until week 13, and total bracing time is 12 weeks. 
 
Participants  
The patient recruitment will be achieved in-house from the emergency clinic and the orthopedic 
surgery department at Bispebjerg and Frederiksberg Hospital. Potential participants are either 
identified by the diagnosing doctor, or by the primary investigator through screening of the 
orthopedic surgery-lists. Furthermore, features of the SP-journal system will be used to support 
recruitment. For patients identified by the diagnosing doctor, once the diagnosis of Achilles 
tendon rupture is established, patients are orally informed about the study and if interested in 
participating they will receive the written attending information (“Deltagerinformation”). Patients 
identified through the orthopedic surgery-lists will be approached by the primary investigator in 
person on the day of surgery and will be given the same oral and written information as those 
identified by the diagnosing doctor. Patients interested in participating will either contact the 
primary investigator or will be approached in person on the day of surgery, to be screened for 
eligibility. The orthopedic surgeons will assess all patients after standard procedures and, if 
surgical intervention is decided, patients will undergo the standard surgical procedure. After 
surgery, patients will be randomized to one of the two rehabilitation groups: 
A) Early mobilization. This constitutes the currently accepted regime and is therefore considered 
the control group.  
B) Delayed mobilization.  
Randomization procedure is performed using a computer-generated block randomization (blocks of 
4) procedure. 
 
Blinding 
Because this is an “open-label” trial the health professionals delivering the interventions and the 
participants will not be blinded to treatment allocation. Outcome assessors will be blinded to 
treatment allocation whenever possible: This is of outmost importance, and participants are 
requested not to disclose their allocation when outcomes are assessed.  

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Sample size calculation  
Based on heel-rise deficit (primary outcome) relative to the uninjured side (uA=76 %, uB=90 %, 
s=16) a sample of n=21 is required to detect a difference with a power of 80% (19). To account for 
drop-outs a sample of 24 in each arm will be recruited. 
 
Outcome assessments 
 
Primary outcome  
The primary outcome is heel-rise height deficit on the injured side relative to the uninjured side at 
one-year follow-up.  
 
Secondary outcomes 
The following outcomes are assessed as secondary outcomes: 
• Heel-rise work.   
• Achilles Tendon Total Rupture Score (ATRS).  
• Gastrocnemius and soleus muscle fascicle length and pennation angle.  
• Gastrocnemius and soleus tendon and lower limb muscle cross-sectional area.  
• Plantarflexion Isokinetic muscle strength. 
• Physical actively level (PAS). 
• Tendon length. 
• Achilles Tendon Resting Angle (ATRA).  
 
 
 
 
 
Population to be analyzed 
To be included in the study, participants must meet the following in- and exclusion criteria: 
 

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Inclusion criteria  
Exclusion criteria 
• Diagnosed with a traumatic, complete 
mid-substance Achilles tendon 
rupture  
• No contraindications for MRI 
• Other injuries affecting their lower 
limb functions 
• Prior Achilles tendon rupture 
• Re-rupture 
• Presented within 14 days from injury 
• Smoking 
• Adult (18 to 60 years) 
• Understand Danish 
• Manage transport to/from the 
hospital on their own 
 
• Systemic diseases influencing tendon 
healing 
• Anticoagulation treatment 
• Inability to follow rehabilitation or 
complete follow-ups 
 
• Immunosuppressive treatment 
including systemic corticosteroid 
treatment. 
 
Intension-to-treat (ITT) 
All participants who are randomized. 
Per protocol (PP) 
All participants who adhere to the major criteria in the protocol and completed the whole study 
period and attended 1 year follow-up. Participants with missing data on any of the variables in the 
model will be excluded from the specific analysis at the specific timepoint.  
 
Analysis 
All outcomes will be reported using descriptive statistics. Normally distributed data by the mean 
and standard deviation and skewed distributions by the median and interquartile range. Binary 
and categorical variables will be presented using counts and percentages. SAS and Prism will be 
used for all statistical analysis. Analyses in addition to the descriptive statistics are described 
below. 
 

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Primary outcome 
The primary analysis will be an assessment of the between group difference in heel-rise height 
deficit on the injured side relative to the uninjured side ((uninjured-injured/uninjured) x 100)) at 
one-year follow-up. Intention-to-treat and per-protocol analysis will be conducted. The criteria for 
being included in the per-protocol analysis is having attended 1 year follow-up tests. An unpaired 
students t-test will be used to analyze the primary outcome (heel-rise deficit) at the primary 
endpoint (one year).  
 
Secondary outcome 
A mixed model (group x time) that includes all timepoints will be used to analyze the secondary 
outcomes and the primary outcome. In addition, a correlation matrix for the changes in secondary 
and primary outcome will be performed, followed by a multiple regression. ATRA will be 
compared with MRI and correlated. 
 
Table of the analysis 
 
OUTCOME 
TIMEPOINTS 
UNPAIRED 
T-TEST 
MIXED MODEL 
CORRELATION 
MULTIPLE 
REGRESSION 
MRI 
Tendon length 
CSA tendon 
CSA muscle 
Free fat fraction 
 
4 
 
x 
x 
x 
ULTRASOUND 
Fascicle length 
Pennation angle 
Thickness muscle 
Doppler tendon 
Thickness tendon 
4 
 
x 
x 
x 
HEELRISE 
Work 
Hight 
Repetitions 
 
2 
 
x 
x 
x 
ATRA 
2 
 
x 
x 
x 
MUSCLE STRENGTH 
1 
x  
 
x 
x 
ATRS 
2 
x 
 
x 
x 
PAS 
2 
x 
 
x 
x 
LIKERT SCALE 
1 
x 
 
 
 

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