Clinical trial NCT01252420: Two Weeks of Low Molecular Weight Heparin for Distal Vein Thrombosis
Official title: Two Weeks of Low Molecular Weight Heparin for Distal Vein Thrombosis (TWISTER)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Venous Thrombosis
Pulmonary Embolism
Keywords: Distal Vein Thrombosis
Proximal Vein Thrombosis
Pulmonary Embolism
Post-thrombotic syndrome
Limited duration treatment
Lead sponsor: Monash Medical Centre
Sponsor class: OTHER
Collaborators: name: Southern Health, Victoria
name: Eastern Health, Victoria
name: Royal Adelaide Hospital, Adelaide
name: Prince of Wales Hospital, Sydney
name: Christchurch Hospital, NZ
name: Auckland City Hospital
name: North Shore Hospital, New Zealand
name: Middlemore Hospital, New Zealand
First posted: 2010-12-03
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Symptomatic recurrence of venous thrombosis (DVT, non fatal and fatal pulmonary embolism) within 3 months.
timeFrame: 3 months
Secondary outcomes:
measure: Asymptomatic proximal thrombus extension at 2 weeks
timeFrame: 2 weeks
measure: Time course of symptom resolution and the proportion of patients with complete resolution at two weeks.
timeFrame: 2 weeks
measure: All-cause mortality
timeFrame: 3 months
measure: Post-thrombotic syndrome
timeFrame: 6 months
measure: Predictors of recurrent or progressive DVT or new PE
timeFrame: 3 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Monash Medical Centre, Southern Health
state: Victoria
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: Canterbury
Study officials:
affiliation: Monash Medical Centre
name: Huyen Tran, MBBs(Hons), MClin Epidem
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Nov;207:33-39. doi: 10.1016/j.thromres.2021.09.004. Epub 2021 Sep 11.