Ximelagatran antithrombotics

Description Results NMA

oral ximelagatran at doses of 24 mg, 36 mg, 48 mg, or 60 mg twice daily (n=1245)

vs.

placebo (n=638)

double-blind

Parallel groups

Sample size: 1245/638

Primary endpoint: death, MI, severe recurrent ischaemia

FU duration: 6 months

dose ranging

non fatal TE events,bleedings and vascular death* 0.71 [0.48; 1.07]

all death 0.99 [0.73; 1.34]

coronary events 1.85 [0.94; 3.61]

vascular death 1.21 [0.77; 1.91]

major bleeding 0.71 [0.44; 1.13]

haemorragic stroke(or intracerebral hemorrhage) 0.44 [0.14; 1.44]

fatal stroke(ischemic+hemorrhagic) 1.11 [0.45; 2.73]

thrombo-embolic event (cerebral or systemic) 0.71 [0.48; 1.07]

ischemic stroke 0.70 [0.45; 1.09]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.70 [0.45; 1.09]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.67 [0.44; 1.01]

systemic thrombo-embolic complication 2.00 [0.37; 10.90]

hypertransaminasemia 7.81 [4.58; 13.32]

non fatal TE events,bleedings and vascular death* 1.38 [0.91; 2.10]

all death 0.94 [0.74; 1.21]

coronary events 0.70 [0.43; 1.16]

major bleeding 0.75 [0.54; 1.03]

haemorragic stroke(or intracerebral hemorrhage) 1.00 [0.14; 7.10]

fatal stroke(ischemic+hemorrhagic) 3.34 [0.92; 12.11]

thrombo-embolic event (cerebral or systemic) 1.38 [0.91; 2.10]

ischemic stroke 1.25 [0.81; 1.93]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.25 [0.81; 1.93]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 1.24 [0.81; 1.89]

systemic thrombo-embolic complication 6.01 [0.72; 49.84]

ximelegatran 20,40,60 mg twice daily (n=187)

vs.

warfarin standard dose(target INR 2-3) (n=67)

-treatment with either NSAI agents or fibrinolytic agents within the week before the start was prohibited -patient previously receiving warfarin were given ximelegatran once INR value was 1.5 or under/after the end of the study patients who stopped ximelegatran began warfarin 12 to 24 h after last intake.

-SPORTIF II is a dose guiding study -66 patient received 20mg,62 received 40mg,59 received 60 mg

Open

Parallel groups

Sample size: 187/67

Primary endpoint: Thrombo-embolic events and bleedings

FU duration: 16 weeks

it is a dose guiding study

ximelagatran 36 mg twice daily (n=1704)

vs.

warfarin standard dose (target INR 2-3) (n=1703)

Aspirin was used concurrently for at least half the period on study drug by 13% patients assigned to ximelagatran and 10% on warfarin(p=0.01).

Open

Parallel groups

Sample size: 1704/1703

Primary endpoint: All stroke or systemic embolism

FU duration: 17.4 months

Premature termination of study treatment was the result of study endpoint (4% warfarin group,3% ximelegatran) and adverse effects(4% warfarin group,8% ximelegatran group:this difference is related to elevation of liver enzymes in some patients treated with ximelegatran). The trial was a non inferiority trial but the primary analysis was only by intention to treat.

ximelegatran 36 mg twice daily (n=1960)

vs.

warfarin standard dose(target INR 2-3) (n=1962)

Double blind

Parallel groups

Sample size: 1960/1962

Primary endpoint: All stroke and systemic embolism

FU duration: 20 months

serious bleeding 0.00 [0.00; NaN]

DVT+PE 0.70 [0.39; 1.26]

DVT+PE 1.71 [1.15; 2.54]

serious bleeding 0.88 [0.32; 2.41]

serious bleeding NaN [NaN; NaN]

DVT+PE 0.83 [0.25; 2.76]

DVT+PE 0.53 [0.38; 0.74]

serious bleeding 2.01 [0.91; 4.42]

serious bleeding 0.86 [0.48; 1.56]

DVT+PE 1.14 [1.00; 1.29]

DVT+PE 0.76 [0.66; 0.88]

serious bleeding 2.89 [1.65; 5.09]

Ximelagatran 8, 12, 18 or 24 mgorally b.d., at least 12 h after surgery for 6–12 days (n=600)

vs.

Enoxaparin 30 mg s.c. b.d.,starting at least 12 h after surgery for 6–12 days (n=0)

double-blind

parallel group

Sample size: 600/0

Primary endpoint:

FU duration: 6–12 days

Ximelagatran 24 mg orally b.d., starting at least 12 h after surgery for 7–12 days (n=906)

vs.

Enoxaparin 30 mg s.c. b.d.,starting at least 12 h after surgery for 7–12 days (n=910)

double-blind

parallel group

Sample size: 906/910

Primary endpoint:

FU duration: 7–12 days

Melagatran 1–4 mg s.c. immediately before surgery, melagatran at 20.00 hours, then ximelagatran 6–24 mg orally b.d. for 6–9 days (n=103)

vs.

Dalteparin 5000 IU o.d., started evening before surgery for 6–9 days (n=0)

open

parallel group

Sample size: 103/0

Primary endpoint:

FU duration: 6–9 days

Melagatran 1–3 mg s.c. immediately before surgery,melagatran same day, then ximelagatran 8–24 mg orally b.d. for 7–10 days (n=1495)

vs.

Dalteparin 5000 IU o.d., started evening before surgery for 7–10 days (n=381)

double-blind

Parallel groups

Sample size: 1495/381

Primary endpoint: deep-vein thrombosis and pulmonary embolism

FU duration: 7–10 days

Melagatran 3 mg s.c. 4–12h after surgery, then ximelagatran24 mg orally b.d. for 7–10 days (n=2788)

vs.

Enoxaparin 40 mg s.c. o.d. 12 h before surgery for 7–10 days (n=0)

double-blind

Sample size: 2788/0

Primary endpoint: venous thromboembolism

FU duration: 8–11 days

Melagatran 2 mg s.c. up to 30 min before surgery, then melagatran 3 mg at least 8 hafter surgery, then ximelagatran 24 mg orally b.d. for 8–11 days (n=2835)

vs.

Enoxaparin 40 mg s.c. o.d.,starting 12 h before surgery for 8–11 days (n=0)

double-blind

parallel group

Sample size: 2835/0

Primary endpoint: venous thromboembolism

FU duration: 8–11 days

Recurrent DVT/DVT extension (symptomatic) 0.17 [0.09; 0.31]

VTA 0.24 [0.15; 0.40]

All-cause mortality 0.86 [0.29; 2.53]

Major hemorrhage 1.20 [0.37; 3.90]

any bleedings 1.21 [0.96; 1.51]

ximelagatran 24 mg twice daily for 18 months (n=612)

vs.

placebo for 18 months (n=611)

double blind

Parallel groups

Sample size: 612/611

Primary endpoint: symptomatic recurrent venous

FU duration: 18 months

extended treatment with Ximelagatran 24mg twice daily after initial anticoagulant treatment for 6 months (n=-9)

vs.

placebo (initial anticoagulant treatment for 6 months) (n=-9)

single blind and outcome ass.

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 18 months

oral ximelagatran (24, 36, 48 or 60 mg twice daily) for 2 weeks (n=-9)

vs.

dalteparin and warfarin for 2 weeks (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

ximelagatran 36 mg twice daily (n=-9)

vs.

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. (n=-9)

double blind

Sample size: -9/-9

Primary endpoint: 28 countries

FU duration: