venous thrombosis clinical trials results

3-6 months versus 1.5-3 months
Pinede, 2001
Long course of therapy (6 months for proximal DVT and/or PE; 12 weeks for calf DVT) by fluindione adjusted for INR range of 2.0 to 3.0
versus
Short oral anticoagulant course (3 months for proximal DVT and/or PE; 6 weeks for isolated calf DVT) by fluindione adjusted for INR range of 2.0 to 3.0
open
Follow-up duration: 15 months after randomizationÛ
France
6 months versus 1.5 months
Schulman, 1995
6 months treatment with warfarin or dicoumarol adjusted for a target INR between 2.0 - 2.85
versus
1.5 months warfarin or dicoumarol adjusted for a target INR between 2.0 - 2.85
open
Follow-up duration: Two years after randomization
Sweden
apixaban (without LMWH) versus LMWH/VKA
AMPLIFY, 2013
NCT00643201
apixaban 10 mg twice daily for 7 days then 5 mg, twice daily, 6 months
versus
conventional therapy: enoxaparin 1mg/kg twice daily until INR>=2 then warfarin for an INR between 2-4, once daikly, 6 months
patients with deep vein thrombosis or pulmonary embolism double blind
Follow-up duration: 6 mo
Botticelli DVT, 2008
NCT00252005
apixaban 5 mg twice-daily, 10 mg twice-daily, or 20 mg once-daily for 84-91 days
versus
low molecular weight heparin followed by vitamin K antagonists
patients with symptomatic deep vein thrombosis open
apixaban 2.5mg versus discontinuation
AMPLIFY-EXT 2.5mg, 2012
NCT00633893
Extended Treatment with apixaban 2.5 mg twice daily 12 months
versus
placebo
patients who have completed their intended treatment for deep vein thrombosis or pulmonary embolism double blind
Follow-up duration: 12 mo
apixaban 2.5mg versus placebo
AMPLIFY EXT 2.5mg, 2013
apixaban (2.5 mg and 5 mg, twice daily)
versus
placebo
patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy
apixaban 5mg versus discontinuation
AMPLIFY-EXT 5mg, 2012
NCT00633893
Extended Treatment with apixaban 5 mg twice daily 12 months
versus
placebo
patients who have completed their intended treatment for deep vein thrombosis or pulmonary embolism double blind
Follow-up duration: 12 mo
apixaban 5mg versus placebo
AMPLIFY EXT 5mg, 2013
apixaban (2.5 mg and 5 mg, twice daily)
versus
placebo
patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy
arvin versus no fibrinolysis
Kakkar (arvin), 1969
streptokinase 500,000 U IV over 30 minutes, 900,000 U every 6 hours for 5 days
versus
heparin 10,000 U over 5 minutes, then 10,000 to 15,000 U every 6 hours for 5 dayslicatio
patients with venographically confirmed DVT of leg of duration < 4 dayssingle blind
UK
aspirin versus discontinuation
WARFASA, 2012
NCT00222677
aspirin, 100 mg daily for 2 years
versus
placebo
patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment double-blind
Follow-up duration: 24.6 mo (median)
ASPIRE, 2012
ACTRN12605000004662
aspirin, at a dose of 100 mg daily up to 4 years
versus
patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism
Follow-up duration: 37.2 montsh (median)
aspirin versus placebo
ASPIRE, 2012
aspirin, at a dose of 100 mg daily, for up to 4 years
versus
placebo
patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism
Follow-up duration: 37.2 months median
WARFASA, 2012
aspirin, 100 mg daily for 2 years
versus
placebo
patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment
Bemiparin versus warfarin
Kakkar, 2003
LMWH, 115 IU/kg qd followed by Bemiparin 3,500 IU qd
versus
A: UFH, 30/40,000IU qd; B: LMWH, 115 IU/kg qd followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 3 mo
caval filter versus no filter
PREPIC, 1998
caval filter
versus
no filter
patients with documented proximal DVT or PE, and considered high risk for pulmonary embolismopen
Follow-up duration: 12 days and 2 years
dabigatran versus discontinuation
RE-SONATE, 2011
NCT00558259
dabigatran 150 mg twice daily for an additional period of 6 months
versus
placebo
Secondary prevention of VTE in patients with VTE who had completed 6-18 months of anticoagulant therapy double-blind
dabigatran versus placebo
RESONATE, 2013
dabigatran at a dose of 150 mg twice daily
versus
placebo
dabigatran versus warfarin
RE-MEDY, 2011
NCT00329238
dabigatran 150 mg twice daily for an additional period of 6 to 36 months
versus
warfarin (to maintain an international normalized ratio of 2.0 to 3.0) for an additional period of 6 to 36 months
Secondary prevention of VTE in patients with VTE who had initially received 3 to 12 months of anticoagulant therapy double-blind
Follow-up duration: 6 to 36 months
REMEDY, 2013
dabigatran at a dose of 150 mg twice daily
versus
Dalteparin versus unfractionated heparin
Holm et al , 1986
Dalteparin Subcutaneous twice daily ajusted for 7 Days, 57-107 U/kg BID
versus
unfractionated heparin subcutaneous twice daily 16000-30000 U

Follow-up duration: Hospital Stay
Bratt et al , 1985
Dalteparin Intravenousv (ajusted) for >=5 Days, 120 U/kg BID
versus
unfractionated heparin intravenous APPTx1.7-3.5

Follow-up duration: 23 Months (mean)
Bratt et al, 1990
Dalteparin Subcutaneous twice daily ajusted for >= 5 Days, 120 U/kg BID
versus
unfractionated heparin intravenous APPTx2-4

Follow-up duration: Hospital stay
Lindmarker et al , 1993
Dalteparin Subcutaneous once daily for >= 5 Days, 200 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-3

Follow-up duration: 6 Months
Dalteparin versus warfarin
Lee, 2003
LMWH, 200 IU/kg qd followed by Dalteparin 150 IU/kg qd
versus
LMWH, 200 IU/kg qd followed by Warfarin target INR 2-3
patients with cancer and objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 6 mo
Das, 1996
UFH followed by Dalteparin 5,000 IU qd
versus
UFH followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 3 mo
Enoxaparin versus acenocoumarol
Veiga, 2000
UFH, APTT 1.5–2.0d followed by Enoxaparin 4,000 IU qd
versus
UFH, APTT 1.5–2.0d followed by Acenocoumarol target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 6-9 mo
Enoxaparin versus coumarin
González-Fajardo, 2008
long-term anticoagulant treatment with enoxaparin during at least 3 months
versus
long-term anticoagulant treatment with coumarin during at least 3 months
patients with symptomatic, unilateral, first-episode DVTopen, blind assessment
Follow-up duration: 1y, 5y
Spain
Enoxaparin versus unfractionated heparin
Simonneau et al , 1993
Enoxaparin Subcutaneous twice daily for 0 Days, 100 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-2.5

Follow-up duration: 3 Months
Enoxaparin versus warfarin
Deitcher, 2003
LMWH: 1a, 1 mg/kg q12h; 1b, 1 mg/kg qd12h followed by Enoxaparin 1a: 1 mg/kg qd; 1b: 1.5 mg/kg qd
versus
LMWH, 1 mg/kg q12h followed by Warfarin target INR 2-3
patients with objective diagnosis of DVTopen
Follow-up duration: 6 mo
Meyer, 2002
LMWH, 1.5 mg/kg qd followed by Enoxaparin 1.5 mg/Kg qd
versus
LMWH, 1.5 mg/kg qd followed by Warfarin target INR 2-3
patients with cancer and objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 3 mo
Gonzalez-Fajardo, 1999
LMWH, 4,000 IU bid followed by Enoxaparin 4,000 IU qd
versus
UFH followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 9 mo
Pini, 1994
UFH, APTT 1.3–1.9 followed by Enoxaparin 4,000 IU qd
versus
UFH, APTT 1.3–1.9 followed by Warfarin target INR 2-3.5
patients with objective diagnosis of DVT by Venography (diagnosed by strain-gauge plethysmography plus D-dimer latex assay and confirmed by venography)open
Follow-up duration: 9 mo
extended dalteparin versus standard treatment
Lee, 2003
Dalteparin 200 IU/kg daily for 1 month followed by 150 IU/kg daily for 5 months
versus
Dalteparin 200 IU/kg daily for 5-7 days followed by wafarin or acecumarol (target INR 2-3) for 6 months
patients with active cancer and with DVT or pulmonary embolism or both, and ECOG 1 or 2outcome assessment blinded
Follow-up duration: 6 months
extended enoxaparin versus standard treatment
Cesarone, 2003
Enoxaparin 100UL/Kg twice daily for 3 months
versus
coumadin (target INR 3) for 3 months.
patients with cancer with DVTNA
Follow-up duration: 3 months
Deitcher, 2006
Enoxaparin 1mg/kg twice daily for 5 days followed by 1-1.5mg/kg daily for 175 days
versus
Enoxaparin 1mg/kg twice daily for 5 days followed by warfarin (target INR 2-3) for a total of 180 days
patients with cancer with DVT and/or PEnone
Follow-up duration: 12 months
Meyer, 2002
Enoxaparin 1.5 mg/kg daily for 3 monthsmag
versus
Enoxaparin 1.5 mg/kg daily for 4 days followed by warfarin (target INR 2-3) for 3 months
patients with cancer (solid or hematological; active or in remission but on treatment); with pulmonary embolism and/or DVT and a minimum life expectancy of 3 monthsoutcome assessment blinded
Follow-up duration: 3 months
extended nadroparin versus standard treatment
Lopez Beret, 2001
Nadroparin 1.025 antiXa IU/10Kg twice daily after aadroparin 1.025AXa IU/10Kg twice daily for 3 days. After 3 months, nadroparin was switched to once daily
versus
acenocoumarol (target INR 2-3) for 3-6 months after nadroparin 1.025AXa IU/10Kg twice daily for 3 days
patients with known malignancy treated for symptomatic DVT of the lower limboutcome assessment blinded
Follow-up duration: 12 months
extended tinzaparin versus standard treatment
Hull, 2006
Tinzaparin 175 antiXa/kg SQ daily for 12 weeks
versus
UFH for 5 days followed by vitamin K antagonist (target INR 2-3) for 12 weeks
patients with cancer (solid or hematological) with proximal DVT with or without PE and with a minimum life expectancy of 3 months imagoutcome assessment blinded
Follow-up duration: 3 months
fondaparinux versus enoxaparin
MATISSE, 2004
fondaparinux 7.5 mg subcutaneously once daily for at least 5 days and until vitamin K antagonists induced an INR greater than 2.0.
versus
enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an INR greater than 2.0.
patients with acute symptomatic deep venous thrombosisdouble blind
Follow-up duration: 3 months
international
fondaparinux versus heparin
MATISSE PE, 2003
fondaparinux subcutaneously once daily
versus
continuous intravenous infusion of unfractionated heparin
patients with acute symptomatic pulmonary embolismopen
Follow-up duration: 3 mo
heparin+phenprocoumon versus phenylbutazone
Nielsen importé, 1994
heparin and phenprocoumon for 3 months
versus
phenylbutazone
open
Denmark
heparin+warfarin versus placebo
Ott importé, 1998
anticoagulants (s.c. heparin followed by oral warfarin) (duration NA)
versus
s.c. saline followed by oral placebo tablets
double blind
Denmark
heparin/dabigatran versus heparin/VKA
RE-COVER, 2009
NCT00291330
dabigatran 150 mg twice daily in a fixed-dose
versus
warfarin dose-adjusted to an INR between 2.0 and 3.0
patients with acute venous thromboembolism , treated with low molecular weight or unfractionated heparin for 5 to 11 daysdouble blind
Follow-up duration: 6 months
RE-COVER II, 2011
NCT00680186
dabigatran, 150 mg twice daily, for 6 months
versus
warfarin, dose-adjusted to an INR of 2.0 and 3.0, for 6 months
patients with acute VTE, treated with low molecular weight or unfractionated heparin for 5 to 11 daysdouble-blind
Follow-up duration: 6 months
31 countries
heparin/edoxaban versus heparin/VKA
Edoxaban Hokusai VTE, 2013
NCT00986154
heparin then edoxaban 60mg daily (30mg if creatine clearnce of 30 to 50 ml/min or <60kg) for 3 to 12 months
versus
heparin then warfarin
patients with acute venous thromboembolism, who had initially received heparin,double-blind
idraparinux versus discontinuation
VanGogh extension, 2007
NCT00071279
once-weekly injections of 2.5 mg of idraparinux for 6 months
versus
placebo
patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted
Follow-up duration: 6 months
idraparinux versus placebo
Van Gogh, 2007
NCT00071279
once-weekly injections of 2.5 mg of idraparinux for 6 months without monitoring
versus
placebo
patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted double-blind
idraparinux versus standard treatment
Van Gogh (subgroup), 2011
once-weekly subcutaneous injection of idraparinux (2.5 mg) for 6 months
versus
standard treatment for three months (8%) or six months (92%)
non-active and active cancer patients with deep venous thrombosis and without pulmonary embolism, included in the Van Gogh DVT clinical trial
Follow-up duration: 6 months
idraparinux (without heparin) versus heparin/VKA
VanGogh DVT, 2007
NCT00067093
subcutaneous idraparinux (2.5 mg once weekly)
versus
heparin followed by an adjusted-dose vitamin K antagonist
patients with deep-vein thrombosis open
Follow-up duration: 3 mo (6 mo)
VanGogh PE, 2007
NCT00062803
subcutaneous idraparinux (2.5 mg once weekly)
versus
heparin followed by an adjusted-dose vitamin K antagonist
patients with pulmonary embolism open
Follow-up duration: 3 mo (6 mo)
LMWH at home versus UFH in hospital
Koopman, 1996
home treatment with twice daily injections of nadroparin at a dose adjusted for patient’s weight;
versus
UH (APTT adjusted dose, continuous intravenous infusion of 1250 IU per hour after initial intravenous bolus of 5000 IU) in hospital.
patients with acute symptomatic proximal DVT proven by venography or duplex scanopen
Follow-up duration: 12 weeks
The Netherlands, France, Italy, New Zealand Australia
Boccalon, 2000
home treatment with sub-cutaneous injection of LMWH (dalteparin sodium, enoxaparin sodium or nadroparin calciumas chosen by the attending physician) at the recommended dose followed by anticoagulant for 6months
versus
Sub-cutaneous injection of LMWH(dalteparin sodium, enoxaparin sodium or nadroparin calcium as chosen by attending physician) at the recommended dose followed by anticoagulant for 6 months initially in hospital for 10 +/- 2 days then at home
patienst with confirmed diagnosis (by ultrasonography or venography) of proximal DVT not more than 30 days before enrolmentNA
Follow-up duration: 6 months
France
Levine, 1996
home treatment by Sub-cutaneous enoxaparin 1 mg per kg body weight twice a day for at least 5 days
versus
UH (APTT adjusted dose, continuous intravenous infusion of 20,000 IU after initial intravenous bolus of 5000 IU) in hospital for at least 5 days
patients with acute proximal DVT proven on venography or duplex scanopen
Follow-up duration: 90 days
Canada
Ramacciotti, 2004
home treatment by once daily Subcutaneous injection of enoxaparin at a dose of 1.5 mg/kg for 5-10 days
versus
in hospital intravenous bolus injection of 5000 IU of UFH followed by intravenous 500 IU/kg/day adjusted to maintain an aPTT of 1.5-2.5 times the normal value for 5-10 days.
patienst with DVT symptoms for greater than or equal to 10 days and proximal lower limb DVT confirmed by duplex ultrasound or venographyopen
Brazil
Daskalopoulos, 2005
home treatment with single sub- cutaneous injection of LMWH (tinzaparin sodium) in a weight adjusted dose (175 anti Xa IU/Kg) daily for 6 months
versus
Intravenous bolus of 5000IU UFH followed by intrvenous infusion of UFH for 5-7 days. APTT was measured after 4 hours of the initiation of heparin administration and was repeated 6 hours thereafter to reach the therapeutic range (ratio: 1.5-2.5). Oral an
patients with acute proximal DVT confirmed by colour duplex UScan not more than 1 week onsetopen
Greece
Chong, 2005
once daily sub-cutaneous injection of enoxaparin 1.5mg/kg for a minimum of 5 days plus 10mg of warfarin for 3 months adjusted to achieve INR above 2 and within range accepted by the investigator
versus
5000 IU bolus of unfractionated heparin (UFH) for a minimum of 5 days plus 10mg warfarin started on day 1 of the treatment for 3 months
patients with diagnosis of symptomatic lower extrimity DVT (proimal or distal) confirmed by either contrast venography and/or ultrasonography, be suitable for treatment in an outpatient setting open
Follow-up duration: 24 months
Australia, New Zealand, Poland, South Africa
low-intensity warfarin versus placebo
PREVENT, 2003
low-intensity warfarin (target INR, 1.5 to 2.0)
versus
placebo
Patients with idiopathic venous thromboembolism who had received full-dose anticoagulationdouble-blind
Follow-up duration: 2.1 years mean
Minoctoparine versus unfractionated heparin
Faivre et al , 1988
Minoctoparine (CY222) Subcutaneous twice daily for 10 Days,155 U/kg BID
versus
unfractionated heparin subcutaneous twice daily APPTx2-3

Follow-up duration: 10 Days
Nadroparin versus acenocoumarol
Lopez-Beret, 2001
LMWH, 1,025 IU/10 kg bid followed by Nadroparin 1,025 IU/10 kg bid
versus
LMWH, 1,025 IU/10 kg bid followed by Acenocoumarol target INR 2-3
patients with objective diagnosis of DVT by compression ultrasonographyopen
Follow-up duration: 6-9 mo
Lopaciuk, 1999
LMWH, 85 UI/kg bid followed by Nadroparin 85 IU/kg qd
versus
LMWH, 85 UI/kg bid followed by Acenocoumarol target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 9 mo
Nadroparin versus unfractionated heparin
Collaborative European Multicentre, 1991
Nadroparin Subcutaneous twice daily for 10 Days, 90 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-2

Follow-up duration: 12 Weeks
Prandoni et al , 1992
Nadroparin Subcutaneous twice daily for >=0 Days, 90 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-2

Follow-up duration: 6 Months
Lopaciuk et al , 1992
Nadroparin Subcutaneous twice daily for 10 Days, 92 U/kg BID
versus
unfractionated heparin subcutaneous twice daily APPTx1.5-2.5

Follow-up duration: 3 Months
once daily dalteparin versus twice daily dalteparin
Holmström, 1992
once daily dalteparin 200 U (anti-FXa)/kg for at least 5 days
versus
twice daily dalteparin 100 U (anti-FXa)/kg for at least 5 days
Patients with a first occurence of DVT in the lower limb, confirmed with phlebographytioopen
Sweden
Partsch, 1996
Fragmin administered 200 IU/kg once daily for at least 7 days
versus
Fragmin 100 IU/kg twice daily for at least 7 days
patients presented with DVT extending into the iliofemoral segment diagnosed by duplex ultrasonographyANA
Austria
once daily enoxaparin versus twice daily enoxaparin
Merli, 2001
enoxaparin 1.5 mg/kg body weight once daily
versus
S.c. enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily
patients with a symptomatic lower-extremity DVT confirmed by venography or ultrasonography (including patients with confirmed PE)double blind
Europe, United States of America and Australia, image/pj
once daily enoxaparin versus UFH
Merli (once daily vs UFH), 2001
Initial therapy with enoxaparin 1.5 mg/kg body weight once daily
versus
Initial therapy with dose-adjusted intravenous unfractionated heparin
patients with a symptomatic lower-extremity DVT confirmed by venography or ultrasonography (including patients with confirmed PE) partialy blinded
Follow-up duration: 3 months
Europe, United States of America and Australia, image/pj
once daily logiparin versus twice daily logiparin
Siegbahn, 1989
Once daily logiparin 150 XaI U/kgp, imag
versus
twice daily logiparin 75 XaI U/kg
patients with a venographically confirmed episode of DVTsingle blind
Sweden and Denmark
once daily nadroparin versus twice daily nadroparin
Charbonnier, 1998
Once daily nadroparin 20,500 (AXa IU/ml)continued for at least 5 days
versus
twice daily nadroparin 10,250 (AXa IU/ml)continued for at least 5 days
patients with acute symptomatic proximal DVT in popliteal vein or above documented by venographydouble blind
Europe
rivaroxaban versus discontinuation
EINSTEIN-extension, 2009
NCT00439725
rivaroxaban 20 mg once-daily for an additional 6 or 12 months
versus
placebo
patients who had completed six to 12 months of anticoagulant treatment for an acute episode of VTEdouble blind
28 countries
rivaroxaban (without LMWH) versus LMWH/VKA
Einstein-DVT Dose-Ranging Study, 2008
rivaroxaban 20, 30, or 40 mg once daily
versus
low-molecular-weight heparin followed by vitamin K antagonists
patients with deep vein thrombosisopen
Einstein-DVT Evaluation, 2010
NCT00440193
rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg daily
versus
enoxaparin 1 mg/kg twice daily >=5 days, then warfarin with target INR between 2-3
Patients with Confirmed Acute Symptomatic Deep-Vein Thrombosis without Pulmonary Embolismopen (assessor-blind)
Einstein-PE Evaluation, 2012
NCT00439777
rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) for 3, 6, or 12 months
versus
standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist
patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosisopen
Follow-up duration: 9.8 months
38 countries
rivaroxaban 10mg versus aspirin
EINSTEIN CHOICE (10mg), 2017
NCT02064439
Rivaroxaban 10 mg once daily for 12 months
versus
ASA (Acetylsalicylic Acid) 100 mg once daily for 12 months
Patients with confirmed symptomatic DVT (Deep Vein Thrombosis) or PE (Pulmonary embolism) who completed 6 or 12 months of treatment of anticoagulation
rivaroxaban 20mg versus aspirin
EINSTEIN CHOICE (20mg), 2017
NCT02064439
Rivaroxaban 20 mg once daily for 12 months
versus
ASA (Acetylsalicylic Acid) 100 mg once daily for 12 months
Patients with confirmed symptomatic DVT (Deep Vein Thrombosis) or PE (Pulmonary embolism) who completed 6 or 12 months of treatment of anticoagulation
rivaroxaban 20mg versus placebo
EISNTEIN EXT, 2010
rivaroxaban alone (20 mg once daily)for an additional 6 or 12 months
versus
placebo
patients who had completed 6 to 12 months of treatment for venous thromboembolism
streptokinase versus no fibrinolysis
Arneson, 1978
streptokinase 250,000 U loading IV, then 100,000 IU/hour IV 72-96 hours
versus
heparin 15,000 IU IV bolus, 30,000 IU infusion IV 72-90 hours¢ßl
inpatients with venographically confirmed DVT extending proximally beyond the calf <5 days duration?single blind
Norway
Common, 1976
hydrocortisone 100 mg IV then streptokinase IV 250,000 U over 30 minutes, then 100,000 U/hour titrated for 72 hours. Followed by IV heparin titrated over 7 days
versus
IV heparin 150 U/kg loading dose then titrated for 10 days
patients with venographically confirmed DVT duration < 14 dayssingle blind
US
Elsharawy, 2002
catheter-directed thrombolysis with streptokinase using popliteal approach.
versus
heparin IV bolus 5000 U, then adjusted continuous infusion. Warfarin begun the same evening
iliofemoral venous thrombosis confirmed by duplex or venography duration < 10 daysicatiosingle blind
Egypt
Schulman, 1986
streptokinase 50,000 IU IV over 15 minutes then 100,000 IU over 12 hours for up to 7 days, titrated. Given with 5000 IU heparin IV over 12 hours. Warfarin begun after streptokinase ended
versus
heparin 5000 IUIVbolus then 30,000 IUper day, titrated for 7 days.Warfarin begun simultaneously
patients with venographically confirmed calf vein thrombosis of duration < 7 days.single blind
Sweden
Tsapogas, 1973
titrated dose of streptokinase IV into ankle veinmage/pj
versus
heparin IV into affected limbitm
patients with DVT confirmed by venogram of duration < 5 days.open
US
Kakkar (streptokinase), 1969
streptokinase 500,000 U IV over 30 minutes, 900,000 U every 6 hours for 5 days
versus
heparin 10,000 U over 5 minutes, then 10,000 to 15,000 U every 6 hours for 5 dayslicatio
patients with venographically confirmed DVT of leg of duration < 4 dayssingle blind
UK
Schweizer (systemic SK), 2000
Systemic streptokinase 3,000,000 U/day over 6 hours in conjunction with heparin for up to 7 days. Premedication: hydrocortisone 100 mg, ranitidine 50 mg, clemastine 2 mg
versus
heparin IV, adjusted
patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 dayssingle blind
Germany
subcutaneous heparin versus intravenous heparin
Krahenbuhl, 1979
subcutaneous sodic heparin 30 000 U daily (mean)
versus
intravenous sodic heparin 30 000 U daily (mean)
Bentley, 1980
subcutaneous calcic heparin 37 000 U daily (mean)
versus
intravenous sodic heparin 36 800 U daily (mean)
Andersson, 1982
subcutaneous sodic heparin 36 800 U daily (mean)
versus
intravenous sodic heparin 33 250 U daily (mean)
Hull, 1986
subcutaneous sodic heparin 32 300 U daily (mean)
versus
intravenous sodic heparin 29 700 U daily (mean)
Doyle, 1987
subcutaneous calcic heparin 29 200 U daily (mean)
versus
intravenous calcic heparin 29 600 U daily (mean)
Walker, 1987
subcutaneous calcic heparin 29 375 U daily (mean)
versus
intravenous calcic heparin 24 384 U daily (mean)
Lopaciuk, 3000
subcutaneous sodic heparin 34 400 U daily (mean)
versus
intravenous sodic heparin 37 000 U daily (mean)
Pini, 1990
subcutaneous calcic heparin 33 800 U daily (mean)
versus
intravenous sodic heparin 31 700 U daily (mean)
Tinzaparin versus acenocoumarol
Romera, 2009
tinzaparin SC 175 IU anti-Xa per kg once daily for 6 months
versus
acenocoumarol for target INR 2-3 for 6 months after initial LMWH (until INR 2-3)
patients with symptomatic proximal DVT of the lowerlimbs confirmed by compression duplex ultrasound scanopen
Follow-up duration: 12 months
Spain
tinzaparin versus dalteparin
Wells (subgroup), 2005
Tinzaparin 175 IU/kg SQ daily (warfarin started simultaneously and continued for 90 days)
versus
dalteparin 200 IU/kg daily for at least 5 days ((warfarin started simultaneously and continued for 90 days)
study subgroup of patients with cancer treated for upper or lower extremity DVT or PE in the outpatient settingoutcome assessment blinded
Follow-up duration: 3 months
Tinzaparin versus unfractionated heparin
Hull et al , 1992
Tinzaparin Subcutaneous once daily for >= Days, 175 U/kg BID
versus
unfractionated heparin intravenous APPTx2-3

Follow-up duration: 3 Months
Tinzaparin versus warfarin
Hull, 2002
LMWH, 175 IU/kg qd followed by Tinzaparin 175 IU/kg qd
versus
UFH 5 d, followed by UFH therapeutic APTT followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 9 mo
tPA versus no fibrinolysis
Goldhaber (tPA alone), 1990
tPA alone 0.05 mg/kg/hour IV over 24 hours, then heparin100U/kg bolus, then 1000 U/hour, adjusted
versus
heparin alone 100 U/kg bolus, then 1000 U/hour
venographically documented DVT, in popliteal ormore proximal veins < 14 days durationsingle blind
US
Schweizer (local tPA), 2000
local tPA 20 mg/day, over 4 hours via pedal vein for 4-7 days. IV heparin given simultaneously at 1000 IU/hour, adjusted
versus
heparin IV, adjusted
patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 dayssingle blind
Germany
Turpie, 1990
tPA + IV heparin
versus
5000 U bolus then 30,000 U/24 hours, adjusted for 7-10 days (+placebo)
patients with venographically confirmed proximal DVT of lower limb of duration < 7 daysdouble blind
Canada
Verhaeghe (high dose), 1989
IV tPA 100 mg on day 1, 50 mg tPA on day 2. 10% of dose given as bolus; heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours
versus
heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours (+placebo)
hospitalised patients with DVT of popliteal or more proximal veins of the lower leg, confirmed by venography of duration < 10 days.double blind
France, Belgium, Switzerland
Goldhaber (tPA+heparin), 1990
tPA 0.05 mg/kg/hour IV over 24 hours and heparin 100U/kg bolus, then 1000 U/hour, adjusted
versus
heparin alone 100 U/kg bolus, then 1000 U/hour.
patients with venographically documented DVT, in popliteal ormore proximal veins < 14 days durationsingle blind
US
Verhaeghe (low dose), 1989
IV tPA 50 mg on day 1, repeated on day 2. 10% of dose given as bolus; heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours
versus
heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours (+placebo)
hospitalised patients with DVT of popliteal or more proximal veins of the lower leg, confirmed by venography of duration < 10 days.double blind
France, Belgium, Switzerland
tPA+heparin versus no fibrinolysis
Schweizer tPA, 1998
tPA 20 mg IV into pedal vein over 4 hours each day for 7 days. Heparin IV given concomitantly, with adjustment
versus
heparin IV, adjusted for 7 days
patients with venographically confirmed DVT of leg duration < 7 days.single blind
Germany
urokinase versus no fibrinolysis
Kiil, 1981
urokinase 200,000 U IV over 24 hours. After 18 hours, heparin loading dose of 15,000 units then 40,000 U/day for 5 days (+placebo)
versus
heparin 40,000 U/day IV for 6 days (+placebo)
patients with venographically confirmed DVT duration < 72 hoursDouble blind
Denmark
Schweizer (urokinase), 1998
Urokinase 100,000 IU/hr IV into pedal vein continuously for 7 days. Heparin IV for 7 days. Plasminogen monitored. Warfarin from day 7 to 12 monthsd=132
versus
heparin IV, adjusted for 7 days
patients with venographically confirmed DVT of leg duration < 7 dayssingle blind
Germany
Schweizer (local urokinase), 2000
Local urokinase 100,000 IU/day infused continuously. Fibrinogen and plasminogen monitored. Heparin IV given concomitantly
versus
heparin IV, adjusted
patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 dayssingle blind
Germany
Schweizer (systemic urokinase), 2000
Systemic urokinase 5,000,000 IU/day over 4 hours for up to 7 days. IV heparin given concomitantly
versus
heparin IV, adjusted
patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 dayssingle blind
Germany
VKA versus control
AUREC FVII, 2009
continue VKA for additional 24 months
versus
discontinuation
patients with first spontaneous VTE and FVIII levels >230 IU/dl after 6 montsh of VKA
Follow-up duration: 37 months mean
DACUS (Siragusa), 2008
NCT00438230
anticoagulants for 9 additional months
versus
no treatment
with a first episode of deep vein thrombosis, treated with OAT for 3 months and with Residual vein thrombosis
DURAC II, 1997
anticoagulant therapy continued indefinitely
versus
six months of oral anticoagulant therapy
patients who had had a second episode of venous thromboembolism
Follow-up duration: 4 years
PROLONG (Palarati), 2006
NCT00264277
resume treatment
versus
discontinue treatment
patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months and with abnormal D-dimer testing 1 month after the discontinuation of anticoagulation
Follow-up duration: 1.4 years
WODIT DVT, 2001
continuation for nine additional months
versus
discontinuation
Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy
Follow-up duration: at least two years
WODIT PE, 2003
Extended oral anticoagulant therapy
versus
patients after a first episode of pulmonary embolismwho had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding
VKA versus placebo
PADIS-PE (Couturaud), 2015
NCT00740883
additional 18-month treatment with warfarin
versus
placebo
patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist double-blind
warfarin versus control
Vitotec, 2009
continuation of warfarin for another 6 months
versus
discontinuation of warfarin
patients with idiopathic DVT After 6 months of standard therapy (heparin/LMWH, warfarin with target INR 2-3) and persistent echogenic masses of over 20% of venous diameter
warfarin versus discontinuation
PROLONG (Palareti), 2006
NCT00264277
prolongation
versus
no anticoagulation
patients with an abnormal d-dimer level 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months
Follow-up duration: 1.4 yeras
PREVENT (Ridker), 2003
extension with low-intensity warfarin (target INR, 1.5 to 2.0)
versus
placebo
Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months
Follow-up duration: 2.1 years
Agnelli, 2003
continuation for 3 or 9 additionnal months of warfarin or other oral anticoagulant was adjusted to achieve a target INR between 2.0 and 3.0.
versus
discontinuation (after 3 months)
patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding after a first episode of pulmonary embolismopen
Follow-up duration: 33 months
Italy
Agnelli, 2001
continuation for 9 additional months; warfarin or acenocoumarol adjusted to achieve a target INR between 2.0 and 3.0
versus
discontinuation (after 3 months months)
Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy open
Follow-up duration: 33 months
Italy
LAFIT (Kearon), 1999
Continuation of the oral anticoagulant therapy up to 24 months, warfarin was adjusted to achieve a target INR between 2.0 and 3.0.
versus
discontinuation (after 3 months)
patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism
ELAET (Kearon), 2004
continuation for 2 additionnal months of warfarin adjusted to achieve a target INR between 2.0 and 3.0.
versus
discontinuation (after 1 months)
double blind
Follow-up duration: 11 months (after randomizatio)
Canada, US
Levine, 1995
continuation for 2 months of warfarin adjusted INR value of 2.0 to 3.0
versus
Discontinue oral anticoagulant therapy (after 1 months)
Patients with venographically confirmed acute proximal DVT who had received four weeks of warfarin after initial heparin and whose four week IPG was normal double blind
Follow-up duration: 11 months after randomization.
Canada, Italy
DURAC (Schulman), 1997
indefinite warfarin or dicoumarol adjusted for a target INR between 2.0 and 2.85
versus
6 months warfarin or dicoumarol adjusted for a target INR between 2.0 and 2.85
open
Follow-up duration: Four years after randomization
Sweden
warfarin versus low intensity warfarin
ELATE, 2003
continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0
versus
target INR of 1.5 to 1.9 (low intensity)
patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism open-label
Follow-up duration: 2.4 years mean
warfarin versus placebo
LAFIT, 1999
warfarin for a further 24 months
versus
placebo
patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolismdouble-blind
Follow-up duration: 10 months
Levine, 1995
continue warfarin (targeted International Normalized Ratio 2.0 to 3.0) for a further eight weeks
versus
placebo
Patients with venographically confirmed acute proximal DVT who had received four weeks of warfarin after initial heparin and whose four week IPG was normal
ximelagatran versus discontinuation
THRIVE III, 2003
ximelagatran 24 mg twice daily for 18 months
versus
placebo for 18 months
patients with venous thromboembolism who had undergone six months of anticoagulant therapydouble blind
Follow-up duration: 18 months
18 countries
ximelagatran versus LMWH/VKA
Fiessinger , 2005
ximelagatran 36 mg twice daily
versus
subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0.
patients with acute deep vein thrombosisdouble blind
ximelagatran versus placebo
Schulman (subgroup), 2003
extended treatment with Ximelagatran 24mg twice daily after initial anticoagulant treatment for 6 months
versus
placebo (initial anticoagulant treatment for 6 months)
study subgroup of patients with active cancer in the previous 5 years treated for DVT or pulmonary embolism for 6 months without recurrencesingle blind and outcome ass.
Follow-up duration: 18 months
THRIVE 3, 2003
ximelagatran (24 mg)
versus
placebo
patients with venous thromboembolism who had undergone six months of anticoagulant therapy
ximelagatran (without LMWH) versus LMWH/VKA
THRIVE I, 2003
oral ximelagatran (24, 36, 48 or 60 mg twice daily) for 2 weeks
versus
dalteparin and warfarin for 2 weeks
Patients with acute DVT