title: The Anticoagulation of Calf Thrombosis (ACT) project: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Half of all lower limb deep vein thrombi (DVT) in symptomatic ambulatory patients are located in the distal (calf) veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT) trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis.
  
  
  METHODS
  ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1) a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2) the incidence of major and minor bleeding episodes; (3) the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4) the incidence of venous thromboembolism (VTE) recurrence at 2 years.
  
  
  CONCLUSIONS
  The ACT trial will explore the feasibility of comparing therapeutic anticoagulation to conservative management in acute distal DVT, within a modern cohort. We also aim to provide contemporary data on clot propagation, bleeding rates and long-term outcomes within both groups. These results will inform the conduct of a definitive study if feasibility is established.
authors.affiliation: Emergency Department, Manchester Royal Infirmary, Central Manchester NHS Foundation Trust, Oxford Road, Manchester, UK. Danielhorner@nhs.net
authors.forename: Daniel
authors.initials: D
authors.lastname: Horner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hogg
authors.forename: Richard
authors.initials: R
authors.lastname: Body
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nash
authors.forename: Kevin
authors.initials: K
authors.lastname: Mackway-Jones
mesh_terms: D000208:Acute Disease; D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D002985:Clinical Protocols; D006801:Humans; D007866:Leg / Q000098:blood supply; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D018401:Sample Size; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants