Evaluation of Potential Off-label Use of Dabigatran Etexilate in Europe

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02240654
• Collaborator: (none)
• Enrollment: 36,573
• Location: 1
• Actual Duration (Months): 17.7
• Patients Per Site Per Month: 2065.3

Study Details

Study Description

Brief Summary

This is a descriptive, observational, multi-country European cross-sectional study of new users of dabigatran etexilate that aims to characterise on- and off-label status and other medical characteristics at the time of the first captured prescription of dabigatran etexilate in each database. The study will be conducted using Cegedim Strategic Database (CSD, France), Danish National Databases (Denmark) and Clinical Practice Research Datalink (CPRD, UK).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation

Detailed Description

Study Design:

Study Design

• Study Type: Observational
• Actual Enrollment: 36573 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: Evaluation of Potential Off-label Use of Dabigatran Etexilate in Europe
• Actual Study Start Date: Nov 28, 2014
• Actual Primary Completion Date: May 20, 2016
• Actual Study Completion Date: May 20, 2016

Arms and Interventions

Arm	Intervention/Treatment
Dabigatran etexilate

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Potential Off-label Use Estimated Among New Users of Dabigatran Etexilate in Each of the Data Sources. [Time period since approval of the SPAF indication in, France: 01 August 2011 to 30 June 2014; Denmark: 01 August 2011 to 30 November 2013; UK: 01 August 2011 to 30 August 2015.]

   Definition of off-label use of oral dabigatran etexilate (DE) was based on use for a disease/medical condition other than labelled indications,as described/documented in the data source used in the respective countries, taking into account the changes in the label within the study period. The prevalence of potential off-label use among new users of DE during the overall study period is calculated as the proportion of patients meeting the definition of off-label use by dividing the number of index prescriptions that represented off-label use by the total number of index prescriptions. Two definitions were applied to estimate potential off-label use based on either recorded diagnoses or proxies: a broad definition of on-label prescribing using codes for disease indication e.g.atrial fibrillation(AF) and a restrictive definition excluding patients with conditions for which the drug is not indicated e.g.valvular AF. SPAF:Stroke & systemic embolism in adult patients with non-valvular AF

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Have at least 1 year of enrolment in the electronic database.

2. Have not been prescribed dabigatran etexilate during the 1-year period prior to the index date.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1160.144.1 Boehringer Ingelheim Investigational Site	Barcelona		Spain

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02240654
• Other Study ID Numbers: 1160.144
• First Posted: Sep 16, 2014
• Last Update Posted: Dec 15, 2017
• Last Verified: Nov 1, 2017

• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

Participant Flow

Recruitment Details	This was a descriptive, observational, non-interventional (NIS) multinational, European cross-sectional study with sources of information for clinical conditions available being highly variable across countries/data sources
Pre-assignment Detail	Because it is not possible to rule out duplicate patients across the 2 French panels, all numbers were calculated stratified by data source, and for France further stratified by panel - i.e., not overall.

Arm/Group Title	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)	Dabigatran Etexilate (Pradaxa®)_France (GPs)	Dabigatran Etexilate (Pradaxa®)_Denmark	Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)	Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)
Arm/Group Description	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of cardiologists in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of general practitioners (GPs) in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in National Health Databases in Denmark (DK) (hospital episodes, dispensed ambulatory medications)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) Hospital Episode Statistics (HES) linkable (primary care information, hospital episodes, dispensed ambulatory medications)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) non-linkable HES (primary care information)
Period Title: Overall Study
STARTED	1706	2813	28619	2150	1285
COMPLETED	1706	2813	28619	2150	1285
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)	Dabigatran Etexilate (Pradaxa®)_France (GPs)	Dabigatran Etexilate (Pradaxa®)_Denmark	Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)	Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)	Total
Arm/Group Description	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of cardiologists in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of general practitioners (GPs) in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in National Health Databases in Denmark (DK) (hospital episodes, dispensed ambulatory medications)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) Hospital Episode Statistics (HES) linkable (primary care information, hospital episodes, dispensed ambulatory medications)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) non-linkable HES (primary care information)	Total of all reporting groups
Overall Participants	1706	2813	28619	2150	1285	36573
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.5 (10.0)	74.0 (10.4)	71.8 (10.9)	74.1 (11.2)	73.1 (11.5)	NA (NA)
Sex: Female, Male (Count of Participants)
Female	NA NaN	1272 45.2%	13567 47.4%	938 43.6%	571 44.4%	NA NaN
Male	NA NaN	1541 54.8%	15052 52.6%	1212 56.4%	714 55.6%	NA NaN

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Potential Off-label Use Estimated Among New Users of Dabigatran Etexilate in Each of the Data Sources.
Description	Definition of off-label use of oral dabigatran etexilate (DE) was based on use for a disease/medical condition other than labelled indications,as described/documented in the data source used in the respective countries, taking into account the changes in the label within the study period. The prevalence of potential off-label use among new users of DE during the overall study period is calculated as the proportion of patients meeting the definition of off-label use by dividing the number of index prescriptions that represented off-label use by the total number of index prescriptions. Two definitions were applied to estimate potential off-label use based on either recorded diagnoses or proxies: a broad definition of on-label prescribing using codes for disease indication e.g.atrial fibrillation(AF) and a restrictive definition excluding patients with conditions for which the drug is not indicated e.g.valvular AF. SPAF:Stroke & systemic embolism in adult patients with non-valvular AF
Time Frame	Time period since approval of the SPAF indication in, France: 01 August 2011 to 30 June 2014; Denmark: 01 August 2011 to 30 November 2013; UK: 01 August 2011 to 30 August 2015.

Outcome Measure Data

Analysis Population Description

The study population included new users of dabigatran etexilate in the study period. New users were defined as those patients who initiated treatment with dabigatran etexilate during the study period and who had not used it during the previous year.

Arm/Group Title	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)	Dabigatran Etexilate (Pradaxa®)_France (GPs)	Dabigatran Etexilate (Pradaxa®)_Denmark	Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)	Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)
Arm/Group Description	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of cardiologists in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of general practitioners (GPs) in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in National Health Databases in Denmark (DK) (hospital episodes, dispensed ambulatory medications)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) Hospital Episode Statistics (HES) linkable (primary care information, hospital episodes, dispensed ambulatory medications)	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) non-linkable HES (primary care information)
Measure Participants	1706	2813	28619	2150	1285
Broad definition	24.1 1.4%	34.0 1.2%	17.1 0.1%	5.7 0.3%	11.5 0.9%
Restrictive definition	37.5 2.2%	44.1 1.6%	29.1 0.1%	17.4 0.8%	25.6 2%

Adverse Events

Adverse Event Reporting Description	International Society for Pharmacoepidemiology and European Medicines Agency guidelines state that NIS studies conducted using medical chart reviews/electronic claims/health care records do not require expedited reporting of suspected Adverse events (AEs)/reactions.Given the type of data used for this study,no suspected AEs/reactions were reported
Arm/Group Title	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)		Dabigatran Etexilate (Pradaxa®)_France (GPs)		Dabigatran Etexilate (Pradaxa®)_Denmark		Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)		Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)
Arm/Group Description	New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of cardiologists in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)		New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) identified from panels of general practitioners (GPs) in Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD) in France (primary care information)		New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in National Health Databases in Denmark (DK) (hospital episodes, dispensed ambulatory medications)		New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) Hospital Episode Statistics (HES) linkable (primary care information, hospital episodes, dispensed ambulatory medications)		New users of Dabigatran etexilate (Pradaxa capsules, 75 mg, 110 mg and 150 mg) in Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK) non-linkable HES (primary care information)
All Cause Mortality
	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)		Dabigatran Etexilate (Pradaxa®)_France (GPs)		Dabigatran Etexilate (Pradaxa®)_Denmark		Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)		Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)		Dabigatran Etexilate (Pradaxa®)_France (GPs)		Dabigatran Etexilate (Pradaxa®)_Denmark		Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)		Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Dabigatran Etexilate (Pradaxa®)_France (Cardiologists)		Dabigatran Etexilate (Pradaxa®)_France (GPs)		Dabigatran Etexilate (Pradaxa®)_Denmark		Dabigatran Etexilate (Pradaxa®)_UK (HES Linkable)		Dabigatran Etexilate (Pradaxa®)_UK (HES Non-linkable)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Clinical information being highly variable across countries was likely to be major driver of different proportions.UK(HES link) is likely to provide most accurate estimate(France and DK data need to be interpreted cautiously because of limited info)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.