Clinical trial NCT02318472: Early Mobilization After Achilles Tendon Rupture
Official title: Effects of Direct Functional Mobilization After Achilles Tendon Rupture on Healing and Outcome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Achilles Tendon Rupture
Deep Venous Thrombosis
Keywords: Microdialysis
Patient related outcome
Heel rise test
Immobilization
functional mobilization
Ultrasound
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: OPED GmbH
First posted: 2014-12-17
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether early mobilization after Achilles tendon rupture can speed up healing, prevent development of venous thromboembolism and improve patient outcome.

Detailed description: Patients with acute Achilles tendon rupture will be screened for eligibility at the Karolinska University Hospital and Södersjukhuset, Stockholm.

One hundred-fifty patients will be included and enrolled and assigned to the interventions either by a third party nurse or by a research nurse. Randomisation will be performed with use of computer-generated random numbers in permuted blocks of four, through an independent software specialist, and consecutively numbered, sealed, opaque envelopes opened after surgery and prior to treatment.

The patients will be randomized to undergo either treatment as usual using plaster cast treatment alone or direct post-operative functional mobilization with a weight-bearing orthosis with adjustable range of motion of the ankle.

The power calculation was based upon data from a recent study reporting a 50% rate of CDU-verified DVT after ATR surgery (Domeij-Arverud et a. 2015). We estimated early functional mobilization (EFM) to confer a 50% risk reduction. Sixty-three patients in each group were required to detect a difference of 25% in the incidence of DVT (two-sided type-I error rate = 5%; power = 80%). We decided to include 150 patients to counteract drop-outs. On recommendations from the ethical committee, a ratio of 2:1 was chosen, since our hypothesis was that the EFM group would perform better.

The endpoint of the first part of the study is tendon healing quantified at 2 weeks by microdialysis followed by quantification of markers for tendon repair. The sample size for the outcome in the microdialysis study was calculated on a difference of the glutamate metabolite of 12 µM between the two groups. For this power analysis, we used a glutamate standard difference of 15 µM resulting from a previous study. It was determined that a sample size of 25 patients per group would be necessary to detect the glutamate difference with 80% power when alpha was set equal to 5%. Anticipating that we would lose 10% of participants enrolled, we plan to enroll 27 patients in each group for microdialysis.

The primary aim of the short-term follow up of this randomized, controlled trial was to assess the efficacy of EFM to reduce the DVT incidence after ATR surgery, at two and six weeks post-operatively, compared to treatment-as-usual, i.e. two weeks of plaster cast followed by four weeks' orthosis immobilization. The secondary aim was to evaluate the effect of patient intrinsic factors (age, BMI, calf circumference, ankle range of motion, pain and fear of movement) and patient extrinsic factors (amount of weightbearing, number of daily steps) on the risk of sustaining a DVT.

The primary aim with the long-term follow up is to investigate the effect of early postoperative functional mobilization compared to immobilization on patient-reported function, health, fear of movement, physical activity level, and differences in functional capacity. The second aim is to explore if the occurrence of DVT postoperatively effects functional outcome in the long-term after surgical treatment of ATR.

Additional aims:

The primary aim of the second part of this study was to assess the number of steps and the amount of loading in a weight bearing orthosis during the first six weeks post-surgical ATR repair. A secondary purpose was to investigate if the amount of loading was correlated to fear of movement or/and pain.

The aim with this substudy is to describe differences between the two groups over time regarding tendon elongation, differences in muscle cross-sectional area and differences in tendon cross-sectional area (on the injured side) and to examine if the differences can predict functional outcome in the long-term and if any of the follow-up occasions are most important for long-term functional outcome.

Few studies have evaluated outcome more than one year after injury. The aim of this substudy is to investigate differences in outcome at 3 years after injury between the patients that sustained a DVT and those who did not sustain a DVT. Another aim is to compare the two intervention groups over 3-years time.

Eligibility criteria: Inclusion Criteria:

* Acute unilateral ATR, operated on within 96 hours
* Age between 18 and 75 years

Exclusion Criteria:

* Inability to give informed consent
* Current anticoagulation treatment (including high dose acetylsalicylic acid)
* Planned follow-up at other hospital
* Inability to follow instructions
* Known kidney failure
* Heart failure with pitting oedema
* Thrombophlebitis
* Thromboembolic event during the previous three months
* Other surgery during the previous month
* Known malignancy
* Haemophilia; and pregnancy

Primary outcomes:
measure: Deep venous thrombosis (DVT)
timeFrame: Six weeks
Secondary outcomes:
measure: Functional outcome - muscular endurance tests (heel-rise)
timeFrame: Four years
measure: Patient-reported outcome - ATRS
timeFrame: Four years
measure: Patient-reported outcome - EQ-5D
timeFrame: One year
measure: Physical activity - PAS
timeFrame: Four years
measure: Patient-reported outcome - The Foot and Ankle Outcome Score (FAOS)
timeFrame: One year
measure: Patient-reported outcome - RAND 36 Health and Quality of Life questionnaire
timeFrame: One year
measure: Patient-reported outcome - Tampa Scale of Kinesiophobia, Swedish version, TSK-SV
timeFrame: One year
measure: Plantar force loading
timeFrame: Six weeks
measure: Patient-reported diary - self-reported loading
timeFrame: Two weeks
measure: Patient-reported diary - pain ratings
timeFrame: Two weeks
measure: Patient-reported diary - steps/day
timeFrame: Two weeks
measure: Calf circumference
timeFrame: Four years
measure: Ankle dorsiflexion
timeFrame: Six weeks
measure: Tendon length measurement
timeFrame: Four years
measure: Tendon thickness measurement
timeFrame: One year
measure: Muscle volume of the calf muscles
timeFrame: One year
measure: Thickness of the calf muscles
timeFrame: One year
measure: Achilles Tendon resting angle (ATRA)
timeFrame: Four years
measure: 3D gait analysis
timeFrame: 6 months
Other outcomes:
measure: Tendon healing using microdialysis
timeFrame: Two weeks
measure: Time to surgery
timeFrame: Within 10 days
measure: Surgeon sex
timeFrame: Surgery is performed within 10 days after injury
measure: Surgeon experience
timeFrame: Surgery is performed within 10 days after injury
Locations:
city: Stockholm
country: Sweden
facility: Karolinska university Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Paul W Ackermann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aufwerber S, Silbernagel KG, Ackermann PW, Naili JE. Comparable Recovery and Compensatory Strategies in Heel-Rise Performance After a Surgically Repaired Acute Achilles Tendon Rupture: An In Vivo Kinematic Analysis Comparing Early Functional Mobilization and Standard Treatment. Am J Sports Med. 2022 Dec;50(14):3856-3865. doi: 10.1177/03635465221129284. Epub 2022 Nov 2.
citation: Chen J, Wang J, Hart DA, Ahmed AS, Ackermann PW. Complement factor D as a predictor of Achilles tendon healing and long-term patient outcomes. FASEB J. 2022 Jun;36(6):e22365. doi: 10.1096/fj.202200200RR.
citation: Aufwerber S, Edman G, Gravare Silbernagel K, Ackermann PW. Changes in Tendon Elongation and Muscle Atrophy Over Time After Achilles Tendon Rupture Repair: A Prospective Cohort Study on the Effects of Early Functional Mobilization. Am J Sports Med. 2020 Nov;48(13):3296-3305. doi: 10.1177/0363546520956677. Epub 2020 Sep 28.
citation: Aufwerber S, Heijne A, Edman G, Silbernagel KG, Ackermann PW. Does Early Functional Mobilization Affect Long-Term Outcomes After an Achilles Tendon Rupture? A Randomized Clinical Trial. Orthop J Sports Med. 2020 Mar 16;8(3):2325967120906522. doi: 10.1177/2325967120906522. eCollection 2020 Mar.
citation: Aufwerber S, Heijne A, Gravare Silbernagel K, Ackermann PW. High Plantar Force Loading After Achilles Tendon Rupture Repair With Early Functional Mobilization. Am J Sports Med. 2019 Mar;47(4):894-900. doi: 10.1177/0363546518824326. Epub 2019 Feb 11.
citation: Alim MA, Svedman S, Edman G, Ackermann PW. Procollagen markers in microdialysate can predict patient outcome after Achilles tendon rupture. BMJ Open Sport Exerc Med. 2016 Jun 10;2(1):e000114. doi: 10.1136/bmjsem-2016-000114. eCollection 2016.