Rupture, Surgical Wound Infection, Venous Thromboembolism, Venous Thrombosis
Conditions
Keywords
Achilles Tendon, Immobilization, Wound Healing, Intermittent Pneumatic Compression, Ultrasonography, Microdialysis
Brief summary
This prospective randomized study aims to determine whether intermittent pneumatic compression (IPC), 75 patients, beneath functional bracing compared to treatment-as-usual in plaster cast, 75 patients, can reduce the Venous Thromboembolism (VTE) incidence and promote healing of sutured acute Achilles tendon ruptures. At two weeks post surgery, the IPC intervention will be ended and both patient groups will be immobilized in an orthosis until follow-up at six weeks. The endpoint of the first part of the study is VTE events. The primary outcome will be the DVT-incidence at two weeks, assessed using screening compression duplex ultrasound (CDU) by two ultrasonographers masked to the treatment allocation. Secondary outcome will be the DVT-incidence at 6 weeks. 1\) Deep Vein Thrombosis (DVT) detected by CDU , 2) isolated calf muscle vein thrombosis (ICMVT) detected by CDU, 3) symptomatic DVT or ICMVT detected by CDU, 4) symptomatic pulmonary embolism detected by computer tomography. The endpoint of the second part of the study is tendon healing quantified at 2 weeks by microdialysis followed by quantification of markers for tendon repair. The endpoint of the third part of the study is the functional outcome of the patients at one year post-operatively using four reliable and valid scores, i.e. the Achilles tendon Total Rupture Score (ATRS), Physical Activity scale (PAS), Foot and Ankle Outcome Score (FAOS) and EuroQol Group's questionnaire (EQ-5D) as well as the validated heel-rise test.
Detailed description
The incidence of DVT after Achilles tendon rupture is as high as 30-40% and patients exhibit a prolonged healing process with variable outcome. Moreover, it has been demonstrated that low molecular weight heparin had no effect on preventing DVT after Achilles tendon surgery. Whether intermittent pneumatic compression (IPC) can prevent DVTs and improve healing after Achilles tendon rupture has to our knowledge not been tested before.
Interventions
6 hours IPC, daily, applied to both calves during two weeks post-operatively. The VenaFlow Elite system (Aircast, Vista, California) uses calf cuffs containing two overlapping air chambers located posteriorly on the leg. As the device cycles, the distal chamber inflates to 52 mm Hg over half a second. During the last 0.2 second of this period, the proximal chamber inflates and reaches 45 mm Hg. After six seconds of inflation the cuff deflates, and the cycle is repeated every minute.
Sponsors
Region Stockholm
DJO Incorporated
Karolinska University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Achilles tendon rupture operated on within 96 hours of diagnose.
Exclusion criteria
1. Inability or refusal to give informed consent for participation in the study 2. Ongoing treatment with anticoagulant therapy 3. Inability to comply with the study instructions 4. Known kidney disorder 5. Heart failure with pitting oedema 6. Thrombophlebitis 7. Recent thromboembolic event (during the preceding 3 months) 8. Recent surgery (during the preceding month) 9. Presence of known malignancy 10. Current bleeding disorder 11. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Venous Thromboembolic Events (VTE) | 2 weeks | At 2 weeks postoperatively the number of participants with VTE events will be assessed by: 1\) DVT detected by compression duplex ultrasound (CDU) , 2) isolated calf muscle vein thrombosis (ICMVT) detected by CDU, 3) symptomatic DVT or ICMVT detected by CDU, 4) symptomatic pulmonary embolism detected by computer tomography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Outcome - Muscular Endurance Tests (Heel-rise) | one year | The functional outcome was assessed at 1year post-operatively by the validated calf muscle endurance test, i.e. heel rise test (Silbernagel KG et al. A new measurement of heel-rise endurance with the ability to detect functional deficits in patients with Achilles tendon rupture. Knee Surg Sports Traumatol Arthrosc. 2010). The Muscle lab linear encoder (Ergotest Technology, Oslo, Norway), was used for data collection. Standardized footwear was used. Patients warmed up before testing. During the heel-rise test, verbal encouragement was used. The patient was instructed to go as high as possible on each heel-rise with a straight knee. A metronome was used for standardized frequency of 30 heel-rises per minute. The test was terminated when the patient stopped or could not maintain frequency. For analysis, the limb symmetry index (LSI, percentage of injured vs. uninjured side) values were used. |
| Venous Thromboembolic Events (VTE) | 6 weeks | At 6 weeks postoperatively the number of participants with VTE events will be assessed by: 1\) DVT detected by compression duplex ultrasound (CDU) , 2) isolated calf muscle vein thrombosis (ICMVT) detected by CDU, 3) symptomatic DVT or ICMVT detected by CDU, 4) symptomatic pulmonary embolism detected by computer tomography. |
| Patient-reported Outcome | One year | The patients' symptoms will be assessed using the Achilles tendon Total Rupture Score (0-100, 100=best) |
| Microdialysis | 2 weeks | At 2 weeks postoperatively in-vivo microdialysis will be performed on as described by Greve et al 2012 (DOI: 10.1111/j.1600-0838.2012.01475.x). In the microdialysate substances will be assessed, eg. markers of tendon callus production, procollagen type I (PINP), by enzymatic quantification. |
| Time From Injury to Surgery | 1 year | Prognostic factor: Time to surgery , i.e. the time from ATR injury to start of the surgical procedure, will be calculated by using the time-point at which the patient sustained the injury as described in the patient journal, as well as the starting time point of the surgery as registered in the computerized operation report. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Surgeon Sex | Surgery will be performed within 10 days of injury | Prognostic factor: All patients are operated on according to a standardized surgical protocol. and the surgeon on duty will perform the surgical repair and no specific surgeon can be selected by the patients. Unknown sex of the operating surgeon will be included as an additional exclusion criterion in the study. |
| Surgeon Experience | Surgery will be performed within 10 days of injury | Prognostic factor: All patients are operated on according to a standardized surgical protocol. and the surgeon on duty will perform the surgical repair and no specific surgeon can be selected by the patients. The experienced group of surgeons will consist of specialists accredited with a specialist licence issued by The Swedish National Board of Health and Welfare. The less experienced group of surgeons will consist of residents. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Routine Care: Plaster Cast Treatment Two weeks of postoperative conventional lower limb plaster cast immobilization in 30 degrees of plantarflexion | 71 |
| Intermittent Pneumatic Compression (IPC) Two weeks of calf IPC by Aircast® VenaFlow® Elite System during immobilization in an orthosis Aicast® XP Walker.
Intermittent pneumatic compression (IPC): 6 hours IPC, daily, applied to both calves during two weeks post-operatively. The VenaFlow Elite system (Aircast, Vista, California) uses calf cuffs containing two overlapping air chambers located posteriorly on the leg. As the device cycles, the distal chamber inflates to 52 mm Hg over half a second. During the last 0.2 second of this period, the proximal chamber inflates and reaches 45 mm Hg. After six seconds of inflation the cuff deflates, and the cycle is repeated every minute. | 69 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incorrect inclusion | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Intermittent Pneumatic Compression (IPC) | Routine Care: Plaster Cast Treatment |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 139 Participants | 69 Participants | 70 Participants |
| Age, Continuous | 40.4 years | 40.9 years | 39.9 years |
| Body mass index | 26.9 Kg/m/m | 27.1 Kg/m/m | 26.7 Kg/m/m |
| Region of Enrollment Sweden | 140 participants | 69 participants | 71 participants |
| Sex: Female, Male Female | 21 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 119 Participants | 61 Participants | 58 Participants |
| Tobacco user Tobacco user: No | 127 participants | 64 participants | 63 participants |
| Tobacco user Tobacco user: Yes | 13 participants | 5 participants | 8 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 71 | 3 / 69 |
| serious Total, serious adverse events | 0 / 71 | 0 / 71 |
Outcome results
Primary
Venous Thromboembolic Events (VTE)
At 2 weeks postoperatively the number of participants with VTE events will be assessed by: 1\) DVT detected by compression duplex ultrasound (CDU) , 2) isolated calf muscle vein thrombosis (ICMVT) detected by CDU, 3) symptomatic DVT or ICMVT detected by CDU, 4) symptomatic pulmonary embolism detected by computer tomography.
Time frame: 2 weeks
Population: Non-compliance was defined by exposure to less than ten hours of IPC. Therefore, two patients were withdrawn on this basis and the treatment group comprised 67 patients at final analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Routine Care: Plaster Cast Treatment | Venous Thromboembolic Events (VTE) | 26 participants |
| Intermittent Pneumatic Compression (IPC) | Venous Thromboembolic Events (VTE) | 14 participants |
Comparison: Domeij-Arverud et al., Bone Joint J 2015;97-B:675-80.p-value: 0.042Chi-squared
p-value: <0.0595% CI: [1.25, 6.32]Regression, Logistic
Secondary
Functional Outcome - Muscular Endurance Tests (Heel-rise)
The functional outcome was assessed at 1year post-operatively by the validated calf muscle endurance test, i.e. heel rise test (Silbernagel KG et al. A new measurement of heel-rise endurance with the ability to detect functional deficits in patients with Achilles tendon rupture. Knee Surg Sports Traumatol Arthrosc. 2010). The Muscle lab linear encoder (Ergotest Technology, Oslo, Norway), was used for data collection. Standardized footwear was used. Patients warmed up before testing. During the heel-rise test, verbal encouragement was used. The patient was instructed to go as high as possible on each heel-rise with a straight knee. A metronome was used for standardized frequency of 30 heel-rises per minute. The test was terminated when the patient stopped or could not maintain frequency. For analysis, the limb symmetry index (LSI, percentage of injured vs. uninjured side) values were used.
Time frame: one year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Routine Care: Plaster Cast Treatment | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of Eccentric power (W) | 78.2 Index of Injured versus uninjured side | Standard Deviation 15.8 |
| Routine Care: Plaster Cast Treatment | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of total concentric work (J) | 66.8 Index of Injured versus uninjured side | Standard Deviation 22.2 |
| Routine Care: Plaster Cast Treatment | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of Heel-rise repetitions | 83.0 Index of Injured versus uninjured side | Standard Deviation 22.5 |
| Routine Care: Plaster Cast Treatment | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of concentric power (W) | 81.3 Index of Injured versus uninjured side | Standard Deviation 24.3 |
| Routine Care: Plaster Cast Treatment | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of average height of heel-rise | 78.5 Index of Injured versus uninjured side | Standard Deviation 14.6 |
| Intermittent Pneumatic Compression (IPC) | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of concentric power (W) | 74.2 Index of Injured versus uninjured side | Standard Deviation 32.3 |
| Intermittent Pneumatic Compression (IPC) | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of average height of heel-rise | 82.5 Index of Injured versus uninjured side | Standard Deviation 17 |
| Intermittent Pneumatic Compression (IPC) | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of Eccentric power (W) | 82.6 Index of Injured versus uninjured side | Standard Deviation 22.9 |
| Intermittent Pneumatic Compression (IPC) | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of Heel-rise repetitions | 84.1 Index of Injured versus uninjured side | Standard Deviation 19.1 |
| Intermittent Pneumatic Compression (IPC) | Functional Outcome - Muscular Endurance Tests (Heel-rise) | LSI of total concentric work (J) | 69.4 Index of Injured versus uninjured side | Standard Deviation 20.1 |
Secondary
Microdialysis
At 2 weeks postoperatively in-vivo microdialysis will be performed on as described by Greve et al 2012 (DOI: 10.1111/j.1600-0838.2012.01475.x). In the microdialysate substances will be assessed, eg. markers of tendon callus production, procollagen type I (PINP), by enzymatic quantification.
Time frame: 2 weeks
Population: Concentration of procollagen type I (PINP) ng/ml.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Routine Care: Plaster Cast Treatment | Microdialysis | 2.05 ng/mL | Standard Deviation 0.78 |
| Intermittent Pneumatic Compression (IPC) | Microdialysis | 3.47 ng/mL | Standard Deviation 1.81 |
Secondary
Patient-reported Outcome
The patients' symptoms will be assessed using the Achilles tendon Total Rupture Score (0-100, 100=best)
Time frame: One year
Population: Achilles tendon Total Rupture Score (0-100, 100=best outcome) is presented here.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Routine Care: Plaster Cast Treatment | Patient-reported Outcome | 78 score on a scale | Standard Deviation 19.3 |
| Intermittent Pneumatic Compression (IPC) | Patient-reported Outcome | 77.8 score on a scale | Standard Deviation 17.2 |
Secondary
Time From Injury to Surgery
Prognostic factor: Time to surgery , i.e. the time from ATR injury to start of the surgical procedure, will be calculated by using the time-point at which the patient sustained the injury as described in the patient journal, as well as the starting time point of the surgery as registered in the computerized operation report.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Routine Care: Plaster Cast Treatment | Time From Injury to Surgery | 62.33 hours | Standard Deviation 24.45 |
| Intermittent Pneumatic Compression (IPC) | Time From Injury to Surgery | 62.18 hours | Standard Deviation 26.19 |
Secondary
Venous Thromboembolic Events (VTE)
At 6 weeks postoperatively the number of participants with VTE events will be assessed by: 1\) DVT detected by compression duplex ultrasound (CDU) , 2) isolated calf muscle vein thrombosis (ICMVT) detected by CDU, 3) symptomatic DVT or ICMVT detected by CDU, 4) symptomatic pulmonary embolism detected by computer tomography.
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Routine Care: Plaster Cast Treatment | Venous Thromboembolic Events (VTE) | 34 participants |
| Intermittent Pneumatic Compression (IPC) | Venous Thromboembolic Events (VTE) | 36 participants |
p-value: 0.737Chi-squared
Other Pre-specified
Surgeon Experience
Prognostic factor: All patients are operated on according to a standardized surgical protocol. and the surgeon on duty will perform the surgical repair and no specific surgeon can be selected by the patients. The experienced group of surgeons will consist of specialists accredited with a specialist licence issued by The Swedish National Board of Health and Welfare. The less experienced group of surgeons will consist of residents.
Time frame: Surgery will be performed within 10 days of injury
Other Pre-specified
Surgeon Sex
Prognostic factor: All patients are operated on according to a standardized surgical protocol. and the surgeon on duty will perform the surgical repair and no specific surgeon can be selected by the patients. Unknown sex of the operating surgeon will be included as an additional exclusion criterion in the study.
Time frame: Surgery will be performed within 10 days of injury