Swedish Multicenter Trial of Outpatient Prevention of Leg Clots

Study Overview
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Brief Summary
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Lower limb immobilization is associated with high risk of complications, i.e. venous thromboembolism (VTE) and failed healing. Pharmacoprophylaxis of VTE is in leg-immobilized patients, however, low- or non-effective and associated with adverse events. Thus, there is a need for novel treatments. This study aims to demonstrate in leg immobilized patients who have suffered an ankle fracture (1000 patients) or an Achilles tendon rupture (400 patients) that adjuvant intermittent pneumatic compression (IPC) therapy, which targets impaired vascular flow, compared to treatment-as-usual with plaster cast, reduces VTE incidence and improves healing.

Detailed Description
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The proposed intervention, intermittent pneumatic compression (IPC) is an evidence-based prevention for VTE in hospitalized patients and used in daily practice. IPC is, however, not currently used on outpatients and it is currently unknown if it reduces the risk of VTE during long term leg-immobilization. Plaster cast and orthosis treatments are currently used in daily practice on Achilles tendon ruptures and ankle fractures. At present there is no consensus about using VTE prophylaxis in leg-immobilized patients. Since pharmacoprophylaxis has shown low- or no VTE preventive effects in leg-immobilization, is not recommended by some guidelines. Furthermore, since all patients will undergo clinical examinations and have DVT-screening performed with compression Doppler ultrasound (CDU) removal of leg immobilization this will comprise an extra security for the included patients to detect a VTE. If a VTE is detected clinical guidelines will be followed by initiating chemical VTE-treatment.

Official Title
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Prevention of Thromboembolism and Failed Healing During Lower Limb Immobilization - Multicenter Study With Adjuvant Intermittent Pneumatic Compression Therapy

Conditions
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Achilles Tendon Rupture, Ankle Fractures, Venous Thromboembolism

Intervention / Treatment
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* Device: Adjuvant IPC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute unilateral Achilles tendon rupture or isolated Ankle Fracture Treatment starts within 10 days in a hospital setting Exclusion Criteria: Inability or refusal to give informed consent for participation in the study Inability to comply with the study instructions Known kidney disorder Heart failure with pitting oedema Presence of known malignancy Current bleeding disorder Pregnancy Planned follow-up at another hospital Pilon fracture

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Leg Immobilization<br>Routine care include that the lower limb will be immobilized in an orthosis or a below-knee plaster cast according to local routines. | |
| Experimental: Adjuvant IPC<br>Leg Immobilization with the addition of IPC. Patients will during lower limb immobilization receive bilateral calf IPC. | Device: Adjuvant IPC<br>* This IPC-system delivers sequential circumferential compression. The IPC device is mobile and should therefore not restrict patient mobilization, but can be taken off if the patient wants to mobilize independently.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous Thromboembolic Events (VTE) | The primary outcome is VTE defined as symptomatic Deep venous Thrombosis (DVT) or asymptomatic DVTs,or symptomatic pulmonary embolism | Up til the time of removal of leg immobilization, approx. 6-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient reported Outcome - ATRS | symptoms will be assessed using the reliable and valid score; the Achilles tendon Total Rupture Score (ATRS) | 6 months and 1 year | 
| Patient reported Outcome - FAOS | symptoms will be assessed using the reliable and valid score; the Foot and Ankle Outcome Score (FAOS) | 6 months and 1 year | 
| Patient reported Outcome - OMAS | symptoms will be assessed using the reliable and valid score; the Olerud-Molander Ankle Score (OMAS) | 6 months and 1 year | 
| Patient reported Outcome - EQ-5D-5L | symptoms will be assessed using the reliable and valid score; EuroQol Group's questionnaire (EQ-5D-5L). | 6 months and 1 year | 
| Functional outcome - muscular endurance tests (heel-rise) | Patient leg function will be measured by a validated endurance test (i.e. the heel-rise test) at 1 year post-injury. | 1 year | 
| Callus production | Microdialysis followed by quantification of procollagens will assess callus production in Achilles tendon healing. | 6 weeks | 
| VTE-preventive mechanisms | VTE-preventive mechanisms will be analyzed at the 6 week visit by assessments of profibrinolysis and coagulation factors as well as by blood-flow quantification . | 6 weeks | 
| Incidence of VTE in patients using low molecular weight heparin(LMWH) with or without adjvant IPC | Efficacy of LMWH with and without the use of IPC as to prevent VTE will be studied in order to confirm the efficency of a commonly used drug for VTE prophylaxis. | 6-8 weeks | 
| Patient mortality | Mortality of patients included will be recorded and investigated for cause of death. If the cause of death is VTE, this will be reported. The overall mortality rate in this study is expected to be low. Mortality will be investigated via patient journals at one year after study inclusion, and at 2 years via national mortality register. | 1year and 2 years | 
| Health economic analyses | Together with Karolinska Institutet, LIME, the trial treatment effects will involve a within-trial evaluation of cost effectiveness integrated into a decision-analytic model of longer run costs and health effects | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Achilles tendon, Microdialysis, Immobilization, Wound healing, Intermittent Pneumatic Compression, Ultrasonography