Anticoagulants Comparative Benefit-risk Ratio in Real Life

An observational study of Atrial Fibrillation, run by Boehringer Ingelheim at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The study is an analysis using the French national health insurance database, six months after the beginning of NOAC launch in the NVAF indication. The aim is to compare the one-year, two-year and three-year benefit-risk (major bleeding, arterial thrombotic events, myocardial infarction (MI), death) between patients… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Atrial Fibrillation
Type of treatment: Pill or oral medicine
How many people: 103,101 participants
Where: 1 siteFrance
Study dates: 1 Mar 2016to 5 Apr 2016
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: New users of NOAC or VKA for NVAF

Who may be able to join

Patients with NVAF with a first reimbursed dispensation of Pradaxa®, Xarelto®, or VKA in 2013, with no other identified indication for anticoagulation; Without any VKA or NOAC (Pradaxa®, Xarelto®, or Eliquis®) reimbursed dispensation for the last 3 years before the first reimbursed dispensation of Pradaxa®, Xarelto®, or VKA

Who cannot join

None

Trial locations and contacts

1 site in 1 country.

France1 site

1160.263.1 Boehringer Ingelheim Investigational Site
Multiple Locations

Other trials in France

About this study

Official title: Engel 2: REal-life aNticoaGulants Comparative bEnefit-risk in Nonvalvular Atrial fibrilLation (NVAF) in France

The study is an analysis using the French national health insurance database, six months after the beginning of NOAC launch in the NVAF indication.

The aim is to compare the one-year, two-year and three-year benefit-risk (major bleeding, arterial thrombotic events, myocardial infarction (MI), death) between patients starting a NOAC and patients starting a VKA for NVAF in 2013

Conditions: Atrial Fibrillation
Medical subject headings: Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02785354
Study group	Role	What they receive
NOAC		New oral anticoagulant groups
VKA		VKA group

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinically Relevant Bleeding
First hospitalization with primary diagnosis (Tenth Revision codes of the International Classification of Diseases (ICD-10 codes)) of:
1. Hemorrhagic stroke,
2. Other critical organ or site bleeding,
3. Other bleeding (gastro-intestinal bleeding, urogenital bleeding and other bleeding subtype).
Measured: One year
Major Bleeding
First hospitalization with primary diagnosis (ICD-10 codes) of:
1. Hemorrhagic stroke,
2. Other critical organ or site bleeding,
3. Other bleeding with transfusion, or acute post-hemorrhagic anemia or death during hospital stay.
Measured: 1 year
Arterial Thrombotic Event
First hospitalization with primary diagnosis (ICD-10 codes) of:
1. Ischemic or undefined stroke,
2. Systemic arterial embolism.
Measured: 1 year
Acute Coronary Syndrome
First hospitalization with primary diagnosis (ICD-10 codes) of:
1. Myocardial infarction (ST-segment elevation Myocardial infarction (STEMI) and non-ST-segment elevation Myocardial infarction(NSTEMI)),
2. Unstable angina.
Measured: One year
Death (All-cause)
All-cause death (cause of death not available in the database).
Measured: 1 year
Composite Criterion (Clinically Relevant Bleeding, Arterial Thrombotic Events, Acute Coronary Syndrome, Death)
First event among clinically relevant bleeding, arterial thrombotic event, acute coronary syndrome, or death defined above.
Measured: One year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 20165 Apr 2016

First posted27 May 2016 (estimated)
Study start1 Mar 2016
Primary completion4 Mar 2016
Study completion5 Apr 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Atrial FibrillationStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 103,101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02785354
Sponsor's protocol ID: 1160.263
Status last verified: Feb 2018
First submitted: 25 May 2016
Last updated: 2 Nov 2018
Results posted: Yes, on ClinicalTrials.gov

Publications

Blin P, Dureau-Pournin C, Benichou J, Cottin Y, Mismetti P, Abouelfath A, Lassalle R, Droz C, Moore N. Comparative Real-Life Effectiveness and Safety of Dabigatran or Rivaroxaban vs. Vitamin K Antagonists: A High-Dimensional Propensity Score Matched New Users Cohort Study in the French National Healthcare Data System SNDS. Am J Cardiovasc Drugs. 2020 Feb;20(1):81-103. doi: 10.1007/s40256-019-00359-z.
PubMed 31254174
Blin P, Dureau-Pournin C, Cottin Y, Benichou J, Mismetti P, Abouelfath A, Lassalle R, Droz C, Moore N. Comparative Effectiveness and Safety of Standard or Reduced Dose Dabigatran vs. Rivaroxaban in Nonvalvular Atrial Fibrillation. Clin Pharmacol Ther. 2019 Jun;105(6):1439-1455. doi: 10.1002/cpt.1318. Epub 2019 Feb 6.
PubMed 30499605

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

All Atrial Fibrillation trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Engel 2: REal-life aNticoaGulants Comparative bEnefit-risk in Nonvalvular Atrial fibrilLation (NVAF) in France
ClinicalTrials.gov ID: NCT02785354
Acronym / sponsor ID: 1160.263
Conditions: Atrial Fibrillation
Study type: Observational
Recruitment status: Completed
Enrolment: 103,101 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 1 Mar 2016 (actual)
Primary completion: 4 Mar 2016 (actual)
Study completion: 5 Apr 2016 (actual)
First posted: 27 May 2016 (estimated)
Results: Posted 2 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study is an analysis using the French national health insurance database, six months after the beginning of NOAC launch in the NVAF indication.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
NOAC	–	–New oral anticoagulant groups
VKA	–	–VKA group

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: New users of NOAC or VKA for NVAF

Key inclusion criteria (1 listed)

Patients with NVAF with a first reimbursed dispensation of Pradaxa®, Xarelto®, or VKA in 2013, with no other identified indication for anticoagulation; Without any VKA or NOAC (Pradaxa®, Xarelto®, or Eliquis®) reimbursed dispensation for the last 3 years before the first reimbursed dispensation of Pradaxa®, Xarelto®, or VKA

Key exclusion criteria (1 listed)

None

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Clinically Relevant Bleeding
Time frame: One year
First hospitalization with primary diagnosis (Tenth Revision codes of the International Classification of Diseases (ICD-10 codes)) of: 1. Hemorrhagic stroke, 2. Other critical organ or site bleeding, 3. Other bleeding (gastro-intestinal bleeding, urogenital bleeding and other bleeding subtype).
Major Bleeding
Time frame: 1 year
First hospitalization with primary diagnosis (ICD-10 codes) of: 1. Hemorrhagic stroke, 2. Other critical organ or site bleeding, 3. Other bleeding with transfusion, or acute post-hemorrhagic anemia or death during hospital stay.
Arterial Thrombotic Event
Time frame: 1 year
First hospitalization with primary diagnosis (ICD-10 codes) of: 1. Ischemic or undefined stroke, 2. Systemic arterial embolism.
Acute Coronary Syndrome
Time frame: One year
First hospitalization with primary diagnosis (ICD-10 codes) of: 1. Myocardial infarction (ST-segment elevation Myocardial infarction (STEMI) and non-ST-segment elevation Myocardial infarction(NSTEMI)), 2. Unstable angina.
Death (All-cause)
Time frame: 1 year
All-cause death (cause of death not available in the database).
Composite Criterion (Clinically Relevant Bleeding, Arterial Thrombotic Events, Acute Coronary Syndrome, Death)
Time frame: One year
First event among clinically relevant bleeding, arterial thrombotic event, acute coronary syndrome, or death defined above.

Results and safety

Results posted to the registry on 2 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dabigatran	27,060	27,060
Rivaroxaban	31,388	31,388
Vitamin K Antagonists	44,653	44,653

Primary outcome: Clinically Relevant Bleeding

Time frame: One year. Number. Unit: participants with event

Measure	Dabigatran (Dabigatran vs VKA) n = 20489	VKA (Dabigatran vs VKA) n = 20489	Rivaroxaban (Rivaroxaban vs VKA) n = 23053	VKA (Rivaroxaban vs VKA) n = 23053
Value	367 (2.2 to 2.7)	668 (4.1 to 4.8)	635 (3.5 to 4.1)	767 (4.2 to 4.8)

Dabigatran (Dabigatran vs VKA) vs VKA (Dabigatran vs VKA): Hazard Ratio (HR): 0.58 (95% CI 0.51 to 0.66), p <0.0001, Fine and Gray model
Rivaroxaban (Rivaroxaban vs VKA) vs VKA (Rivaroxaban vs VKA): Hazard Ratio (HR): 0.83 (95% CI 0.75 to 0.92), p = 0.0006, Fine and Gray model

Population analysed: Patients (pts) with a first dispensing (dispen.) of DOAC or VKA in 2013 for NVAF. For each comparison (dabigatran versus VKA and rivaroxaban versus VKA), patients were matched 1:1 on the date of the first drug (DOAC or VKA) dispensing (± 2 weeks (wks.)), gender, age at index date (± 1 year (yr)) and high-dimensional propensity score (hdPS, ± 0.05).

Primary outcome: Major Bleeding

Time frame: 1 year. Number. Unit: participants with events

Measure	Dabigatran (Dabigatran vs VKA) n = 20489	VKA (Dabigatran vs VKA) n = 20489	Rivaroxaban (Rivaroxaban vs VKA) n = 23053	VKA (Rivaroxaban vs VKA) n = 23053
Value	178 (1.0 to 1.4)	341 (2.0 to 2.5)	280 (1.5 to 1.9)	417 (2.2 to 2.7)

Dabigatran (Dabigatran vs VKA) vs VKA (Dabigatran vs VKA): Hazard Ratio (HR): 0.55 (95% CI 0.46 to 0.66), p <0.0001, Fine and Gray model
Rivaroxaban (Rivaroxaban vs VKA) vs VKA (Rivaroxaban vs VKA): Hazard Ratio (HR): 0.68 (95% CI 0.58 to 0.79), p <0.0001, Fine and Gray model

Population analysed: Patients with a first dispensing of DOAC or VKA in 2013 for NVAF. For each comparison (dabigatran versus VKA and rivaroxaban versus VKA), patients were matched 1:1 on the date of the first drug (DOAC or VKA) dispensing (± 2 weeks), gender, age at index date (± 1 year) and high-dimensional propensity score (hdPS, ± 0.05).

Primary outcome: Arterial Thrombotic Event

Time frame: 1 year. Number. Unit: participants with events

Measure	Dabigatran (Dabigatran vs VKA) n = 20489	VKA (Dabigatran vs VKA) n = 20489	Rivaroxaban (Rivaroxaban vs VKA) n = 23053	VKA (Rivaroxaban vs VKA) n = 23053
Value	226 (1.4 to 1.8)	321 (1.9 to 2.4)	343 (1.8 to 2.2)	351 (1.9 to 2.3)

Dabigatran (Dabigatran vs VKA) vs VKA (Dabigatran vs VKA): Hazard Ratio (HR): 0.75 (95% CI 0.63 to 0.88), p = 0.0007, Fine and Gray model
Rivaroxaban (Rivaroxaban vs VKA) vs VKA (Rivaroxaban vs VKA): Hazard Ratio (HR): 0.98 (95% CI 0.85 to 1.14), p = 0.8341, Fine and Gray model

Primary outcome: Acute Coronary Syndrome

Time frame: One year. Number. Unit: participants with events

Measure	Dabigatran (Dabigatran vs VKA) n = 20489	VKA (Dabigatran vs VKA) n = 20489	Rivaroxaban (Rivaroxaban vs VKA) n = 23053	VKA (Rivaroxaban vs VKA) n = 23053
Value	176 (1.1 to 1.4)	238 (1.4 to 1.8)	230 (1.2 to 1.5)	277 (1.4 to 1.8)

Dabigatran (Dabigatran vs VKA) vs VKA (Dabigatran vs VKA): Hazard Ratio (HR): 0.79 (95% CI 0.65 to 0.95), p = 0.0147, Fine and Gray model
Rivaroxaban (Rivaroxaban vs VKA) vs VKA (Rivaroxaban vs VKA): Hazard Ratio (HR): 0.84 (95% CI 0.71 to 1.00), p = 0.0501, Fine and Gray model

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dabigatran	0 of 0	0 of 0	Not reported
Rivaroxaban	0 of 0	0 of 0	Not reported
Vitamin K Antagonists	0 of 0	0 of 0	Not reported

Limitations and caveats (from the sponsor): DOAC \& VKA were prescribed by physicians in their daily practice,with differences for pts \& disease characteristics,including stroke \& bleeding risk factors.To control this pts were 1:1 matched on date of 1st dispensing, gender,age \& hdPS.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31254174Blin P, Dureau-Pournin C, Benichou J, Cottin Y, Mismetti P, Abouelfath A, Lassalle R, Droz C, Moore N. Comparative Real-Life Effectiveness and Safety of Dabigatran or Rivaroxaban vs. Vitamin K Antagonists: A High-Dimensional Propensity Score Matched New Users Cohort Study in the French National Healthcare Data System SNDS. Am J Cardiovasc Drugs. 2020 Feb;20(1):81-103. doi: 10.1007/s40256-019-00359-z.
Derived from this study: PubMed 30499605Blin P, Dureau-Pournin C, Cottin Y, Benichou J, Mismetti P, Abouelfath A, Lassalle R, Droz C, Moore N. Comparative Effectiveness and Safety of Standard or Reduced Dose Dabigatran vs. Rivaroxaban in Nonvalvular Atrial Fibrillation. Clin Pharmacol Ther. 2019 Jun;105(6):1439-1455. doi: 10.1002/cpt.1318. Epub 2019 Feb 6.

Related trials for Atrial Fibrillation

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Atrial Fibrillation, run by Boehringer Ingelheim at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinically Relevant Bleeding (time frame: One year). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02785354, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.