| 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 days | single 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 ultrasonography | open 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 embolism | open 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 ultrasonography | open 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 Venography | open Follow-up duration: 3 mo |
| edoxaban versus dalteparin | |||
| Hokusai-VTE Cancer, 2017 NCT02073682 | low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily. Treatment was given for atleast 6 months and up to 12 months. versus subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily | patients with cancer who had acute symptomatic or incidental venous thromboembolism | open label |
| 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 Venography | open 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 DVT | open, 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 DVT | open 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 ultrasonography | open 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 Venography | open 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 | |||
| CLOT (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 2 | outcome 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 DVT | NA 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 PE | none 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 months | outcome 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 limb | outcome 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 imag | outcome 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 thrombosis | double 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 embolism | open 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 days | double 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 days | double-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 scan | open 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 enrolment | NA 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 scan | open 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 venography | open 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 onset | open 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 anticoagulation | double-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 ultrasonography | open 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 Venography | open 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 phlebographytio | open 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 ultrasonographyA | NA 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 DVT | single 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 venography | double blind Europe |
| rivaroxaban versus dalteparin | |||
| SELECT D, 2018 | rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months) versus dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) | patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lowerextremity proximal deep vein thrombosis (DVT) | open-design |
| 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 VTE | double blind 28 countries |
| rivaroxaban versus enoxaparin | |||
| EINSTEIN (subgroup), 2014 | rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily versus (enoxaparin1·0 mg/kg twice daily and warfarin or acenocoumarol; international normalised ratio 2·0–3·0 | subgroup analysis of patients with active cancer (either at baseline or diagnosed during the study) who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials | |
| 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 thrombosis | open |
| 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 Embolism | open (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 thrombosis | open 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 days | single 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 daysicatio | single 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 days | single 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 days | single 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 scan | open 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 setting | outcome 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 ultrasonography | open 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 duration | single 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 days | single 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 days | double 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 duration | single 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 hours | Double 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 days | single 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 days | single 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 days | single 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 embolism | open 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 thromboembolism | double-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 therapy | double 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 thrombosis | double 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 recurrence | single 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 | |
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