Clinical trials of dabigatran - TrialResults-center.org

pathology

Demonstrated benefit and harm

acute coronary syndrome

versus placebo and control

No demonstrated result for efficacy

meta-analysis

atrial fibrillation

versus anticoagulant

No demonstrated result for efficacy

dabigatran 150mg inferior to warfarin standard dose in terms of Gastrointestinal major bleeding in RE-LY (150mg), 2009

meta-analysis

Trial	control	p<0.05	harm	NS
PETRO (150mg), 2007	dabigatran 150mg vs warfarin standard dose
RE-LY (150mg), 2009	dabigatran 150mg vs warfarin standard dose	haemorragic stroke(or intracerebral hemorrhage) 0.26 [0.14; 0.49] fatal stroke(ischemic+hemorrhagic) 0.67 [0.51; 0.89] non fatal stroke 0.63 [0.43; 0.92] fatal bleeding 0.82 [0.67; 1.00] thrombo-embolic event (cerebral or systemic) 0.66 [0.53; 0.82] ischemic stroke 0.76 [0.59; 0.97] All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.64 [0.51; 0.81] Life threatening major bleeding 0.82 [0.67; 1.00]	Gastrointestinal major bleeding 1.50 [1.20; 1.89]	all death 0.88 [0.77; 1.00] coronary events 1.29 [0.99; 1.69] vascular death 0.85 [0.72; 1.00] major bleeding 0.93 [0.81; 1.07] Non–life threatening Major bleeding 1.08 [0.90; 1.30] systemic thrombo-embolic complication 0.85 [0.39; 1.84]
RE-LY (110mg), 2009	dabigatran 110mg vs warfarin standard dose	major bleeding 0.80 [0.69; 0.93] haemorragic stroke(or intracerebral hemorrhage) 0.31 [0.17; 0.56] Life threatening major bleeding 0.68 [0.56; 0.84]		all death 0.91 [0.80; 1.03] vascular death 0.90 [0.77; 1.06] fatal stroke(ischemic+hemorrhagic) 0.95 [0.74; 1.23] non fatal stroke 0.87 [0.62; 1.23] thrombo-embolic event (cerebral or systemic) 0.91 [0.74; 1.11] ischemic stroke 1.11 [0.89; 1.39] thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.92 [0.75; 1.12] All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.92 [0.74; 1.14] Gastrointestinal major bleeding 1.11 [0.87; 1.42] Non–life threatening Major bleeding 0.95 [0.79; 1.15] systemic thrombo-embolic complication 0.79 [0.36; 1.73]
RE-LY 150mg (2nd prevention subgroup)	dabigatran 150mg vs warfarin	haemorragic stroke(intracerebral hemorrhage) 0.27 [0.10; 0.72] intra cranial hemorrhage(intracerebral hemorrhage + hematomas) 0.41 [0.21; 0.80]		thromboembolic event(cerebral or systemic) 0.76 [0.53; 1.09] thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.76 [0.53; 1.09]
RE-LY 110mg (2nd prevention subgroup) , 2010	dabigatran 100mg vs warfarin	haemorragic stroke(intracerebral hemorrhage) 0.11 [0.03; 0.44] intra cranial hemorrhage(intracerebral hemorrhage + hematomas) 0.20 [0.08; 0.48]		thromboembolic event(cerebral or systemic) 0.85 [0.59; 1.22] thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.85 [0.59; 1.22]
phase 2 dabigatran	dabigatran vs warfarin standard dose

Trial	Treatments	Patients	Method
PETRO (150mg), 2007	dabigatran 150 mg twice daily (alone or combined with 81- or 325-mg aspirin) (n=166) vs. warfarin administered to achieve an international normalized ratio of 2 to 3 for (n=70) factorial design: Three doses of dabigatran etexilate (50, 150, and 300 mg twice daily) were combined in a 3 3 factorial fashion with no aspirin or 81- or 325-mg aspirin once daily.	patients with AF at high risk for thromboembolic events	double blind Factorial plan Sample size: 166/70 Primary endpoint: bleedings FU duration: 12 weeks
RE-LY (150mg), 2009	dabigatran 150 mg twice a day (n=6076) vs. warfarin adjusted-dose to a 2.0 to 3.0 INR (n=6022) 3 arms: dabigatran 110 mg, 150mg and warfarin	Patients With Non-Valvular Atrial Fibrillation	open (blind assessment) Parallel groups Sample size: 6076/6022 Primary endpoint: stroke or systemic embolism FU duration: 2 y (median)
RE-LY (110mg), 2009	dabigatran 110 mg twice a day (n=6015) vs. warfarin adjusted dose to a 2-3 INR (n=6022) 3 arms: dabigatran 110 mg, 150mg and warfarin	Patients With Non-Valvular Atrial Fibrillation	open (blind assessment) Parallel groups Sample size: 6015/6022 Primary endpoint: stroke or systemic embolism FU duration: 2 y (median)
RE-LY 150mg (2nd prevention subgroup)	dabigatran 150mg daily (n=-9) vs. warfarin (n=-9)	patients with a prior stroke or transient ischemic attack	open Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 2 y sub group ( 20% of the overall study population in RE-LY)
RE-LY 110mg (2nd prevention subgroup) , 2010	dabigatran 110mg daily (n=-9) vs. warfarin (n=-9)	patients with a prior stroke or transient ischemic attack	open Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 2 y sub group ( 20% of the overall study population in RE-LY)
phase 2 dabigatran	Dabigatran 110, 220, 300 mg twice daily (n=-9) vs. warfarin (n=-9)	patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent)	open Parallel groups Sample size: -9/-9 Primary endpoint: major bleeding event, , FU duration:

post acute coronary syndromes

versus placebo and control

No demonstrated result for efficacy

meta-analysis

post myocardial infarction

versus placebo and control

No demonstrated result for efficacy

meta-analysis

thrombosis prevention

versus Low molecular weight heparin

No demonstrated result for efficacy

dabigatran 220mg inferior to enoxaparin (US regimen) in terms of total VTE and all-cause mortality in RE-MOBILIZE (220mg), 2008 (knee surgery patients)

dabigatran 150mg inferior to enoxaparin in terms of symptomatic DVT in RE-NOVATE (150mg), 2007 (hip surgery patients)

dabigatran 150mg inferior to enoxaparin (US regimen) in terms of distal DVT in RE-MOBILIZE (150mg), 2008 (knee surgery patients)

dabigatran 150mg inferior to enoxaparin (US regimen) in terms of total VTE and all-cause mortality in RE-MOBILIZE (150mg), 2008 (knee surgery patients)

meta-analysis

Trial	control	harm	NS
RE-MOBILIZE (220mg), 2008	dabigatran 220mg vs enoxaparin (US regimen)	total VTE and all-cause mortality 1.23 [1.03; 1.47]	coronary events 1.05 [0.48; 2.31] major bleeding 0.42 [0.15; 1.19] proximal DVT 1.49 [0.67; 3.33] distal DVT 1.20 [0.99; 1.45] major VTE (fatal and non fatal DVT,PE) 1.51 [0.79; 2.91] major or clinically relevant non-major bleeding 0.86 [0.52; 1.41]
RE-MODEL (220mg), 2007	dabigatran 220mg vs enoxaparin (europe regimen)		death 1.01 [0.06; 16.19] coronary events 1.26 [0.40; 3.99] major bleeding 1.14 [0.46; 2.78] proximal DVT 0.82 [0.40; 1.69] distal DVT 1.02 [0.85; 1.21] asymptomatic DVT 1.00 [0.85; 1.18] total VTE and all-cause mortality 0.97 [0.82; 1.13] major VTE (fatal and non fatal DVT,PE) 0.73 [0.36; 1.47] symptomatic DVT 0.13 [0.02; 1.01] major or clinically relevant non-major bleeding 1.11 [0.76; 1.63]
RE-NOVATE (220mg), 2007	dabigatran 220mg vs enoxaparin		death ∞ [NaN; ∞] major bleeding 1.29 [0.70; 2.37] proximal DVT 0.57 [0.32; 1.00] distal DVT 0.94 [0.53; 1.66] non-fatal PE 1.70 [0.41; 7.09] asymptomatic DVT 0.73 [0.49; 1.08] total VTE and all-cause mortality 0.90 [0.63; 1.29] major VTE (fatal and non fatal DVT,PE) 0.78 [0.48; 1.27] symptomatic DVT 6.03 [0.73; 49.98]
RE-MODEL (150mg), 2007	dabigatran 150mg vs enoxaparin (europe regimen)		death 0.98 [0.06; 15.70] major bleeding 0.99 [0.39; 2.47] proximal DVT 1.03 [0.54; 1.98] distal DVT 1.07 [0.91; 1.27] non-fatal PE ∞ [NaN; ∞] asymptomatic DVT 1.10 [0.94; 1.29] total VTE and all-cause mortality 1.07 [0.92; 1.25] major VTE (fatal and non fatal DVT,PE) 1.08 [0.58; 2.01] symptomatic DVT 0.37 [0.10; 1.37] major or clinically relevant non-major bleeding 1.22 [0.84; 1.78]
RE-NOVATE (150mg), 2007	dabigatran 150mg vs enoxaparin	symptomatic DVT 8.89 [1.13; 70.07]	death NaN [NaN; NaN] coronary events 0.72 [0.31; 1.68] major bleeding 0.83 [0.42; 1.63] proximal DVT 0.90 [0.55; 1.49] distal DVT 1.50 [0.90; 2.50] non-fatal PE 0.33 [0.03; 3.16] asymptomatic DVT 1.15 [0.82; 1.63] total VTE and all-cause mortality 1.28 [0.93; 1.78] major VTE (fatal and non fatal DVT,PE) 1.09 [0.70; 1.70]
RE-MOBILIZE (150mg), 2008	dabigatran 150mg vs enoxaparin (US regimen)	distal DVT 1.33 [1.10; 1.59] total VTE and all-cause mortality 1.33 [1.12; 1.58]	death ∞ [NaN; ∞] major bleeding 0.42 [0.15; 1.17] non-fatal PE 0.00 [0.00; NaN] major VTE (fatal and non fatal DVT,PE) 1.36 [0.70; 2.63] major or clinically relevant non-major bleeding 0.82 [0.49; 1.34]
RE-NOVATE 2	dabigatran 220mg vs enoxaparin		coronary events 0.99 [0.06; 15.86]

Trial	Treatments	Patients	Method
RE-MOBILIZE (220mg), 2008	dabigatran etexilate 220 mg for 12-15 days (n=862) vs. Enoxaparin 30mg SC BID after surgery for 12-15 days (n=876)	Total knee replacement	double blind Parallel groups Sample size: 862/876 Primary endpoint: total VTE and all-cause mortality FU duration: 12-15 days, median 14d
RE-MODEL (220mg), 2007	dabigatran etexilate 220 mg q.d. 6-10 days (n=694) vs. Enoxaparin 40 mg q.d. for 6-10 days (n=699)	patients undergoing total knee replacement	double blind Sample size: 694/699 Primary endpoint: total VTE and all-cause mortality FU duration: 6-10 days, mean 8 days
RE-NOVATE (220mg), 2007	dabigatran etexilate 220 mg q.d. for 28-35 days (n=1157) vs. Enoxaparin 40 mg q.d. for 23-35 days (n=1162) 3 arms dabigatran 220mg, 150mg and placebo	Total hip replacement	double blind Parallel groups Sample size: 1157/1162 Primary endpoint: total VTE and all-cause mortality FU duration: 28-35 days, median 33d
RE-MODEL (150mg), 2007	dabigatran etexilate 150 mg q.d. for 6-10 days (n=708) vs. Enoxaparin 40 mg q.d. for 6-10 days (n=699)	Total knee replacement	double blind Parallel groups Sample size: 708/699 Primary endpoint: total VTE and all-cause mortality FU duration: 6-10 days, mean 8 days
RE-NOVATE (150mg), 2007	dabigatran etexilate 150 mg q.d. 28-35 days (n=1174) vs. Enoxaparin 40 mg q.d. for 28-25 days (n=1162) 3 arms dabigatran 220mg, 150mg and placebo	Total hip replacement	double blind Sample size: 1174/1162 Primary endpoint: total VTE and all-cause mortality FU duration: 28-35 days, median 33d
RE-MOBILIZE (150mg), 2008	dabigatran etexilate 150 mg q.d. for 12-15 days (n=877) vs. enoxaparin 30 mg SC BID after surgery for 12-15 days (n=876)	Total knee replacement	double blind Sample size: 877/876 Primary endpoint: total VTE and all-cause mortality FU duration: 12-15 days, median 14d
RE-NOVATE 2	dabigatran 220mg once daily for 28-35 Days (n=1010) vs. enoxaparin 40mg subcutaneous once daily for 28-35 Days (n=1003)	patients undergoing total hip-replacement surgery	double-blind Parallel groups Sample size: 1010/1003 Primary endpoint: venous thromboembolism or death FU duration: 28-35 days (mean 32d)