Swedish Multicenter Trial of Outpatient Prevention of Leg Clots (StopLegClots)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Venous Thromboembolism; Ankle Fractures; Achilles Tendon Rupture
• Intervention / Treatment: Device: Adjuvant IPC

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 1400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simon Svedman, MD; Email: Simon.svedman@ki.se
• Study Contact Backup: Name: Luigi Belcastro, RN; Phone Number: +46724641144; Email: luigi.belcastro@sll.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital
    • Contact: Simon Svedman, MD; Email: Simon.svedman@ki.se
    • Contact: Luigi Belcastro, RN; Phone Number: +46724641144; Email: luigi.belcastro@sll.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Leg Immobilization; 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; Leg Immobilization with the addition of IPC. Patients will during lower limb immobilization receive bilateral calf IPC.	Device: Adjuvant IPC; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Istituto Ortopedico Rizzoli; Sahlgrenska University Hospital, Sweden; University Hospital, Akershus; Danderyd Hospital; Uppsala University Hospital; Stockholm South General Hospital; Helsingborgs Hospital; Gävle Hospital; Höglandssjukhuset Eksjö; Norrtälje Hospital; Östersund Hospital; Uddevalla Hospital; Norra Älvsborgs Länssjukhus; Lugano Regional Hospital; Alingsås Lasarett
• Investigators: Principal Investigator: Paul W Ackermann, MD, PhD, Karolinska University Hospital, 171 76 Stockholm, SWEDEN

Publications and helpful links

General Publications

• Arverud ED, Anundsson P, Hardell E, Barreng G, Edman G, Latifi A, Labruto F, Ackermann PW. Ageing, deep vein thrombosis and male gender predict poor outcome after acute Achilles tendon rupture. Bone Joint J. 2016 Dec;98-B(12):1635-1641. doi: 10.1302/0301-620X.98B12.BJJ-2016-0008.R1.
• Domeij-Arverud E, Ackermann PW. Deep Venous Thrombosis and Tendon Healing. Adv Exp Med Biol. 2016;920:221-8. doi: 10.1007/978-3-319-33943-6_21.
• Domeij-Arverud E, Labruto F, Latifi A, Nilsson G, Edman G, Ackermann PW. Intermittent pneumatic compression reduces the risk of deep vein thrombosis during post-operative lower limb immobilisation: a prospective randomised trial of acute ruptures of the Achilles tendon. Bone Joint J. 2015 May;97-B(5):675-80. doi: 10.1302/0301-620X.97B5.34581.
• Abdul Alim M, Domeij-Arverud E, Nilsson G, Edman G, Ackermann PW. Achilles tendon rupture healing is enhanced by intermittent pneumatic compression upregulating collagen type I synthesis. Knee Surg Sports Traumatol Arthrosc. 2018 Jul;26(7):2021-2029. doi: 10.1007/s00167-017-4621-8. Epub 2017 Jul 1.
• Svedman S, Alkner B, Berg HE, Domeij-Arverud E, Jonsson K, Nilsson Helander K, Ackermann PW. STOP leg clots-Swedish multicentre trial of outpatient prevention of leg clots: study protocol for a randomised controlled trial on the efficacy of intermittent pneumatic compression on venous thromboembolism in lower leg immobilised patients. BMJ Open. 2021 May 20;11(5):e044103. doi: 10.1136/bmjopen-2020-044103.

Helpful Links

• Official study site

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 16, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Intermittent Pneumatic Compression; Wound healing; Microdialysis; Ultrasonography; Immobilization; Achilles tendon
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Fractures, Bone; Wounds and Injuries; Leg Injuries; Embolism and Thrombosis; Ankle Injuries; Rupture; Thromboembolism; Venous Thromboembolism; Ankle Fractures
• Other Study ID Numbers: 2017-00202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared on reasonable requests.
• IPD Sharing Time Frame: After completion of the study.
• IPD Sharing Access Criteria: Data will be shared on reasonable requests to the steering committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No