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NCT01671007

GLORIA-AF Registry Program (Phase II/III - EU/EEA Member States)

Completed Results posted Last updated 31 December 2020
What this trial tests

trial in Stroke in 10,471 participants. Completed in 13 December 2019.

Timeline
22 August 2012
Primary endpoint
13 December 2019
13 December 2019

Quick facts

Lead sponsorBoehringer Ingelheim
StatusCompleted
Study typeOBSERVATIONAL
Enrollment10,471
Start date22 August 2012
Primary completion13 December 2019
Estimated completion13 December 2019
Sites522 locations across Italy, Ireland, Poland, Croatia, Denmark, Netherlands, Belgium, Sweden

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) Primary · From baseline visit 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) and Vitamin K Antagonist (VKA) only. In case of multiple events for a patient, the first event was considered. Unknown death was imputed by multiple imputation. 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 bootstrapping approach was used to obtain the 95% confidence in

GroupValue95% CI
Dabigatran Etexilate - Baseline2.301.86 – 2.73
Vitamin K Antagonist (VKA) - Baseline3.022.54 – 3.54
Incidence Rate of Vascular Composite Outcome (Stroke, Systemic Embolism, Myocardial Infarction and Vascular Death) Primary · From baseline visit 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) and Vitamin K Antagonist (VKA) only. In case of multiple events for a patient, the first event was considered. Unknown death was imputed by multiple imputation. 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 bootstrapping approach was used to obtain the 95% confidence interval of the incidence rate.

GroupValue95% CI
Dabigatran Etexilate - Baseline1.911.52 – 2.32
Vitamin K Antagonist (VKA) - Baseline2.361.93 – 2.82
Incidence Rate of Stroke or Systemic Embolism Primary · From baseline visit 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) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.690.45 – 0.94
Vitamin K Antagonist (VKA) - Baseline1.010.76 – 1.30
Incidence Rate of Stroke Primary · From baseline visit 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) and Vitamin K Antagonist (VKA) 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 - Baseline0.640.42 – 0.89
Vitamin K Antagonist (VKA) - Baseline0.960.70 – 1.22
Incidence Rate of Transient Ischaemic Attack (TIA) Primary · From baseline visit 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) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.300.16 – 0.47
Vitamin K Antagonist (VKA) - Baseline0.260.12 – 0.41
Incidence Rate of Systemic Embolism (SEE) Primary · From baseline visit 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 (SEE) on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.070.00 – 0.16
Vitamin K Antagonist (VKA) - Baseline0.060.00 – 0.14
Incidence Rate of Pulmonary Embolism (PE) Primary · From baseline visit 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 pulmonary embolism (PE) on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.090.02 – 0.18
Vitamin K Antagonist (VKA) - Baseline0.060.00 – 0.14
Incidence Rate of Major Bleeding Events Primary · From baseline visit 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 major bleeding events on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only. Major bleeding was defined as meeting one or more of the following criteria: Overt bleeding associated with a reduction in haemoglobin of at least 20 grams per liter or leading to a transfusion of at least 2 units of blood or packed cells; Symptomatic bleeding in a critical area or organ: Intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding or pericardial bleeding; Life-threatening

GroupValue95% CI
Dabigatran Etexilate - Baseline0.730.49 – 0.98
Vitamin K Antagonist (VKA) - Baseline1.421.09 – 1.75
Incidence Rate of Life-threatening Bleeding Events Primary · From baseline visit 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 life-threatening bleeding events on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only. Life-threatening bleeding was defined as meeting one or more of the following criteria: Symptomatic intracranial bleed; Reduction in haemoglobin of at least 50 grams per liter; Transfusion of at least 4 units of blood or packed cells, associated with hypotension requiring the use of intravenous inotropic agents; Necessitated surgical intervention; Fatal bleeding.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.500.31 – 0.71
Vitamin K Antagonist (VKA) - Baseline1.040.77 – 1.34
Incidence Rate of Vascular Death Primary · From baseline visit 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 death on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.760.51 – 1.02
Vitamin K Antagonist (VKA) - Baseline1.000.73 – 1.29
Incidence Rate of Myocardial Infarction Primary · From baseline visit 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 myocardial infarction on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline0.340.18 – 0.53
Vitamin K Antagonist (VKA) - Baseline0.450.27 – 0.64
Incidence Rate of All-cause Death Primary · From baseline visit 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 all-cause death on restricted set that included Dabigatran etexilate (DE) and Vitamin K Antagonist (VKA) only.

GroupValue95% CI
Dabigatran Etexilate - Baseline2.081.69 – 2.51
Vitamin K Antagonist (VKA) - Baseline3.272.80 – 3.77

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline visit until study completion or discontinuation, up to 3 years of follow-up.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dabigatran Etexilate - at Least Once During the Study
Serious: 79/2385 (3%)
Deaths: 116/2385
Vitamin K Antagonist (VKA) - at Least Once During the Study
Serious: 157/3258 (5%)
Deaths: 264/3258
Rivaroxaban - at Least Once During the Study
Serious: 92/2576 (4%)
Deaths: 166/2576
Apixaban - at Least Once During the Study
Serious: 99/2934 (3%)
Deaths: 207/2934
Edoxaban - at Least Once During the Study
Serious: 10/368 (3%)
Deaths: 17/368
Acetylsalicylic Acid (ASA) - at Least Once During the Study
Serious: 70/1940 (4%)
Deaths: 141/1940
Antiplts Other Than ASA - at Least Once During the Study
Serious: 14/427 (3%)
Deaths: 33/427

Serious adverse events (177 terms)

ReactionSystemDabigatran 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 - …
EpistaxisRespiratory, thoracic and mediastinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Lower gastrointestinal haemorrhageGastrointestinal disorders
Cerebral haemorrhageNervous system disorders
HaematuriaRenal and urinary disorders
HaematomaVascular disorders
Ischaemic strokeNervous system disorders
Transient ischaemic attackNervous system disorders
Rectal haemorrhageGastrointestinal disorders
Subdural haematomaInjury, poisoning and procedural complications
International normalised ratio increasedInvestigations
Cardiac failureCardiac disorders
FallInjury, poisoning and procedural complications
Haemorrhage intracranialNervous system disorders
Haemorrhagic strokeNervous system disorders
Urogenital haemorrhageRenal and urinary disorders
HaemorrhageVascular disorders
Blood loss anaemiaBlood and lymphatic system disorders
MelaenaGastrointestinal disorders
Subdural haemorrhageInjury, poisoning and procedural complications
BradycardiaCardiac disorders
Myocardial infarctionCardiac disorders
Eye haemorrhageEye disorders

Most-reported serious reactions: Epistaxis, Gastrointestinal haemorrhage, Upper gastrointestinal haemorrhage, Anaemia, Lower gastrointestinal haemorrhage, Cerebral haemorrhage, Haematuria, Haematoma.

Data from ClinicalTrials.gov NCT01671007 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 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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry.
    Lip GYH, Kotalczyk A, Teutsch C, Diener HC, et al · · 2022 · cited 25× · PMID 35294625 · DOI 10.1007/s00392-022-01996-2
  8. Dabigatran versus vitamin K antagonists for atrial fibrillation in clinical practice: final outcomes from Phase III of the GLORIA-AF registry.
    Huisman MV, Teutsch C, Lu S, Diener HC, et al · · 2022 · cited 22× · PMID 35294623 · DOI 10.1007/s00392-021-01957-1

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