Two Weeks of Low Molecular Weight Heparin for Distal Vein Thrombosis (TWISTER)

Two Weeks of Low Molecular Weight Heparin for Distal Vein Thrombosis (TWISTER)

The purpose of this study is to determine whether a limited duration of treatment (two weeks of low molecular weight treatment) is a safe and effective treatment for distal deep vein thrombosis of the lower limb.

Study Overview

• Status: Unknown
• Conditions: Venous Thrombosis; Pulmonary Embolism
• Intervention / Treatment: Drug: Enoxaparin

Detailed Description

Approximately 50% of symptomatic episodes of deep vein thrombosis (DVT) will be confined to the calf veins (distal DVT). The proportion of distal DVT that propagate to the proximal veins, increasing the risk of pulmonary embolism, is not known. The best treatment of isolated distal DVT is therefore controversial and options include no treatment, follow-up scanning and treatment of only those patients with thrombus propagating to proximal veins, and full anticoagulation for periods ranging from 2 weeks to 3 months.

There is good evidence that the 3-month thromboembolic risk in patients with a negative CUS that is limited to the proximal veins is low, in the order of 1%. Previous studies have demonstrated that patients treated with a short period of anticoagulation (4-6 weeks) have a low risk of developing recurrent DVT or PE. In addition, the specificity of CUS for distal DVT is lower than that for proximal DVT, increasing the proportion of false positive findings, making it likely that a proportion of patients diagnosed with distal DVT are treated unnecessarily, with the attendant risks of major and fatal haemorrhage.

The need for anticoagulation of patients with distal DVT to prevent recurrent DVT is therefore uncertain, however a survey of current practice suggested that most patients with this condition currently receive antithrombotic therapy. The impact of anticoagulation on initial patient symptoms, and the subsequent risk of the post-thrombotic syndrome are also unclear, and may be a possible alternative justification for antithrombotic therapy.

In this proposed multicentre, prospective, cohort study, we plan to determine if a shorter duration of anticoagulation (minimum 2 weeks) is a safe and effective treatment for isolated distal vein thrombosis.

• Study Type: Interventional
• Enrollment (Anticipated): 330
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Not yet recruiting
      • Prince of Wales Hospital
      • Contact: Tim Brighton, MBBs, MD; Phone Number: +61293829013; Email: Tim.Brighton@SESIAHS.HEALTH.NSW.GOV.AU
      • Principal Investigator: Tim Brighton, MBBs, MD
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Not yet recruiting
      • Royal Adelaide Hospital
      • Contact: Simon McRae, MBBs, BMedSci; Phone Number: +61 448882279
      • Principal Investigator: Simon McRae, MBBs, BMedSci
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre, Southern Health
      • Contact: Eileen Merriman, MBChB; Phone Number: +61 450011998; Email: eileen.merriman@southernhealth.org.au
      • Contact: Huyen Tran, MBBS, BClinEpi; Phone Number: +61 408780785; Email: huyen.tran@southernhealth.org.au
      • Principal Investigator: Huyen Tran, MBBs, MClinEp
      • Sub-Investigator: Eileen Merriman, MBChB
      • Sub-Investigator: Sanjeev Chunilal, MBChB
• New Zealand
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Not yet recruiting
      • Christchurch Hospital
      • Contact: Mark Smith, MBChB; Phone Number: +64 3 3640640; Email: mark.smith@cdhb.govt.nz
      • Principal Investigator: Mark Smith, MBChB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18 years or older with acute symptomatic provoked or unprovoked distal vein thrombosis (axial or muscular veins but not involving trifurcation or distal popliteal vein)
• Absence of symptomatic pulmonary embolism

Exclusion Criteria:

• DVT involving trifurcation or more proximal leg veins on imaging
• Prior DVT
• Active malignancy ie present at time of diagnosis, or on treatment, or treatment completed within 3 months
• Ongoing risk factors for propagation e.g. immobility (>50% of day in bed or ≥72 hours), plaster cast or non-weight bearing
• Other indication for therapeutic anticoagulation (e.g. AF)
• Active gastro-oesophageal ulceration or bleeding
• Other high risk for bleeding (e.g. recent neurosurgery, vascular retinopathy, coagulopathy)
• Platelet count <80 x 109/L
• Renal impairment (CrCl <30ml/min) • Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Symptomatic recurrence of venous thrombosis (DVT, non fatal and fatal pulmonary embolism) within 3 months.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		3 months
Asymptomatic proximal thrombus extension at 2 weeks		2 weeks
Time course of symptom resolution and the proportion of patients with complete resolution at two weeks.	Time course of symptom resolution including time to complete resolution of symptoms, and the proportion of patients with complete resolution at two weeks.	2 weeks
Post-thrombotic syndrome		6 months
Predictors of recurrent or progressive DVT or new PE		3 months

Collaborators and Investigators

• Sponsor: Monash Medical Centre
• Collaborators: Middlemore Hospital, New Zealand; Prince of Wales Hospital, Sydney; Auckland City Hospital; Southern Health, Victoria; Eastern Health, Victoria; Royal Adelaide Hospital, Adelaide; Christchurch Hospital, NZ; North Shore Hospital, New Zealand
• Investigators: Principal Investigator: Huyen Tran, MBBs(Hons), MClin Epidem, Monash Medical Centre

Publications and helpful links

General Publications

• Merriman E, Chunilal S, Brighton T, Chen V, McRae S, Ockelford P, Curnow J, Tran H, Chong B, Smith M, Royle G, Crowther H, Slocombe A, Tran H. Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study). Thromb Res. 2021 Sep 11;207:33-39. doi: 10.1016/j.thromres.2021.09.004. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): November 1, 2013
• Study Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: July 20, 2010
• First Submitted That Met QC Criteria: December 2, 2010
• First Posted (Estimate): December 3, 2010

Study Record Updates

• Last Update Posted (Estimate): December 6, 2010
• Last Update Submitted That Met QC Criteria: December 3, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: Pulmonary Embolism; Distal Vein Thrombosis; Proximal Vein Thrombosis; Post-thrombotic syndrome; Limited duration treatment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: DDVTANZ