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NCT01468701

GLORIA-AF Registry Program - Second and Third Phases

Completed Results posted Last updated 29 March 2021
What this trial tests

trial in Stroke in 37,235 participants. Completed in 10 January 2020.

Timeline
7 November 2011
Primary endpoint
10 January 2020
10 January 2020

Quick facts

Lead sponsorBoehringer Ingelheim
StatusCompleted
Study typeOBSERVATIONAL
Enrollment37,235
Start date7 November 2011
Primary completion10 January 2020
Estimated completion10 January 2020
Sites666 locations across Hong Kong, Colombia, Japan, Ecuador, Taiwan, South Korea, Lebanon, Russia

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Stroke or Atrial Fibrillation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase II Primary · From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.

Incidence rate of composite outcome which includes events of Stroke, systemic embolism, myocardial infarction, life-threatening bleeding events and vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only. In case of multiple events for a patient, the first event was considered.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase II)2.061.74 – 2.42
Incidence Rate of Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction, Life-threatening Bleeding Events and Vascular Death) - Phase III Primary · From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.

Incidence rate of composite outcome which includes events of Stroke, systemic embolism, myocardial infarction, life-threatening bleeding events and vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. In case of multiple events for a patient, the first event was considered. Unknown cause of death was imputed by multiple imputation. Counts were based on the average of the 20 restricted data sets. The average of the 20 incidence rates from the 20 imputed datasets were used to obtain the point estimate of the incid

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase III)2.211.88 – 2.57
Vitamin K Antagonist (VKA) - Baseline (Phase III)3.232.83 – 3.62
Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase II Primary · From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.

Incidence rate of vascular composite outcome including events of stroke, systemic embolism, myocardial infarction and vascular death on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only. In case of multiple events for a patient, the first event was considered.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase II)1.741.45 – 2.07
Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) - Phase III Primary · From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.

Incidence rate of vascular composite outcome including events of stroke, systemic embolism, myocardial infarction and vascular death on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. In case of multiple events for a patient, the first event was considered. Unknown death was imputed by multiple imputation. Counts were based on the average of the 20 restricted data sets. The average of the 20 incidence rates from the 20 imputed datasets were used to obtain the point estimate of the incidence rate that is reported here. The bo

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase III)1.911.59 – 2.24
Vitamin K Antagonist (VKA) - Baseline (Phase III)2.622.27 – 2.96
Incidence Rate of Stroke or Systemic Embolism - Phase III Primary · From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.

Incidence rate of stroke or systemic embolism on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase III)0.800.61 – 1.01
Vitamin K Antagonist (VKA) - Baseline (Phase III)1.000.80 – 1.22
Incidence Rate of Stroke - Phase II Primary · From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.

Incidence rate of stroke on all eligible patients excluding prescribed but not taken set for Dabigatran etexilate (DE) of phase II only is presented. Stroke is an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke included ischemic or hemorrhagic or uncertain classification.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase II)0.650.48 – 0.87
Incidence Rate of Stroke - Phase III Primary · From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.

Incidence rate of stroke on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only. Stroke is an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke included ischemic or hemorrhagic or uncertain classification.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase III)0.770.58 – 0.97
Vitamin K Antagonist (VKA) - Baseline (Phase III)0.960.76 – 1.17
Incidence Rate of Transient Ischaemic Attack (TIA) - Phase II Primary · From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.

Incidence rate of transient ischaemic attack (TIA) on on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase II)0.210.12 – 0.34
Incidence Rate of Transient Ischaemic Attack (TIA) - Phase III Primary · From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.

Incidence rate of transient ischaemic attack (TIA) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase III)0.290.17 – 0.42
Vitamin K Antagonist (VKA) - Baseline (Phase III)0.320.21 – 0.45
Incidence Rate of Systemic Embolism (SE) - Phase II Primary · From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.

Incidence rate of systemic embolism (SE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase II)0.040.01 – 0.12
Incidence Rate of Systemic Embolism (SE) - Phase III Primary · From baseline visit of phase III until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days/ VKA+ 6 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 3 years.

Incidence rate of systemic embolism (SE) on restricted set that included Dabigatran etexilate (DE) of phase III and Vitamin K Antagonist (VKA) of phase III only.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase III)0.040.00 – 0.09
Vitamin K Antagonist (VKA) - Baseline (Phase III)0.050.01 – 0.09
Incidence Rate of Pulmonary Embolism (PE) - Phase II Primary · From baseline visit of Phase II until end of initial treatment regimen episode (minimum date of permanent stop of DE + 3 days, start date of other treatments - 1 day, and date of study completion/discontinuation), up to 2 years.

Incidence rate of pulmonary embolism (PE) on all eligible patients excluding prescribed but not taken set that included Dabigatran etexilate (DE) of phase II only is presented.

GroupValue95% CI
Dabigatran Etexilate - Baseline (Phase II)0.070.02 – 0.16

Adverse events — posted to ClinicalTrials.gov

Time frame: Phase (Ph) II: From baseline visit of Phase II until Phase II completion or discontinuation, up to 2 years of follow-up. Only patients who were prescribed Dabigatran etexilate at baseline of Phase II were followed up. Phase III: From baseline visit of Phase III until study completion or discontinuation, up to 3 years of follow-up for all patients irrespective of their antithrombotic treament.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dabigatran Etexilate - Baseline (Phase II)
Serious: 985/4943 (20%)
Deaths: 184/4943
Dabigatran Etexilate - at Least Once During Phase III of the Study
Serious: 118/4477 (3%)
Deaths: 199/4477
Vitamin K Antagonist (VKA) - at Least Once During Phase III of the Study
Serious: 296/5894 (5%)
Deaths: 465/5894
Rivaroxaban - at Least Once During Phase III of the Study
Serious: 185/5177 (4%)
Deaths: 292/5177
Apixaban - at Least Once During Phase III of the Study
Serious: 217/6024 (4%)
Deaths: 392/6024
Edoxaban - at Least Once During Phase III of the Study
Serious: 16/686 (2%)
Deaths: 23/686
Acetylsalicylic Acid (ASA) - at Least Once During Phase III of the Study
Serious: 225/6263 (4%)
Deaths: 469/6263
Antiplts Other Than ASA - at Least Once During Phase III of the Study
Serious: 19/780 (2%)
Deaths: 46/780

Serious adverse events (592 terms)

ReactionSystemDabigatran Etexilate - Bas…Dabigatran Etexilate - at …Vitamin K Antagonist (VKA)…Rivaroxaban - at Least Onc…Apixaban - at Least Once D…Edoxaban - at Least Once D…Acetylsalicylic Acid (ASA)…Antiplts Other Than ASA - …
Atrial fibrillationCardiac disorders
Cardiac failureCardiac disorders
DeathGeneral disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Cardiac failure congestiveCardiac disorders
PneumoniaInfections and infestations
Myocardial infarctionCardiac disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Lower gastrointestinal haemorrhageGastrointestinal disorders
Angina pectorisCardiac disorders
Cerebrovascular accidentNervous system disorders
AnaemiaBlood and lymphatic system disorders
Ischaemic strokeNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
SyncopeNervous system disorders
Sinus node dysfunctionCardiac disorders
Transient ischaemic attackNervous system disorders
BradycardiaCardiac disorders
Subdural haematomaInjury, poisoning and procedural complications
OsteoarthritisMusculoskeletal and connective tissue disorders
HaematuriaRenal and urinary disorders
Renal failureRenal and urinary disorders
Acute myocardial infarctionCardiac disorders

Most-reported serious reactions: Atrial fibrillation, Cardiac failure, Death, Gastrointestinal haemorrhage, Cardiac failure congestive, Pneumonia, Myocardial infarction, Dyspnoea.

Data from ClinicalTrials.gov NCT01468701 adverse events section.

Sponsor's own description

In this part of the Registry Program patients with non-valvular atrial fibrillation (AF) at risk for stroke are enrolled to characterize the target population and to collect real world data on important outcome events. For administrative purposes the study is divided into two protocol numbers: 1160.129 for all non-EU (European Union) and non-EEA (European Economic Area) countries, and 1160.136 for EU and EEA countries. The total number of patients enrolled in both protocols is estimated to be 48,000 patients, and all these patients will be included in the data analysis for study 1160.129.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2.
    Huisman MV, Rothman KJ, Paquette M, Teutsch C, et al · · 2017 · cited 212× · PMID 28209218 · DOI 10.1016/j.jacc.2016.11.061
  2. Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry.
    Mazurek M, Huisman MV, Rothman KJ, Paquette M, et al · · 2017 · cited 71× · PMID 29212125 · DOI 10.1160/th17-08-0555
  3. Evaluation of bleeding in patients receiving direct oral anticoagulants.
    Hellenbart EL, Faulkenberg KD, Finks SW. · · 2017 · cited 64× · PMID 28860793 · DOI 10.2147/vhrm.s121661
  4. Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.
    Romiti GF, Corica B, Mei DA, Bisson A, et al · · 2024 · cited 45× · PMID 38589864 · DOI 10.1186/s12916-024-03373-4
  5. Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry.
    Romiti GF, Corica B, Proietti M, Mei DA, et al · · 2023 · cited 32× · PMID 37753446 · DOI 10.1016/j.eclinm.2023.102039
  6. Global Oral Anticoagulation Use Varies by Region in Patients With Recent Diagnosis of Atrial Fibrillation: The GLORIA-AF Phase III Registry.
    Bayer V, Kotalczyk A, Kea B, Teutsch C, et al · · 2022 · cited 30× · PMID 35243870 · DOI 10.1161/jaha.121.023907
  7. Changes in anticoagulant prescription patterns over time for patients with atrial fibrillation around the world.
    Kozieł M, Teutsch C, Bayer V, Lu S, et al · · 2021 · cited 29× · PMID 34386125 · DOI 10.1002/joa3.12588
  8. Incidence and Risk Factors for Residual Adverse Events Despite Anticoagulation in Atrial Fibrillation: Results From Phase II/III of the GLORIA-AF Registry.
    Ding WY, Lane DA, Gupta D, Huisman MV, et al · · 2022 · cited 28× · PMID 35876418 · DOI 10.1161/jaha.122.026410

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing