BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME).

This study has been completed.

Sponsor:

Collaborator:

Eli Lilly and Company

Information provided by (Responsible Party):

Boehringer Ingelheim

ClinicalTrials.gov Identifier:

NCT01131676

First received: May 26, 2010

Last updated: April 7, 2016

Last verified: April 2016

History of Changes

Results First Received: April 7, 2016

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
Condition:	Diabetes Mellitus, Type 2
Interventions:	Drug: BI 10773 low dose Drug: Placebo BI 10773 high dose Drug: BI 10773 high dose Drug: Placebo BI 10773 low dose

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients randomised to treatments in 1:1:1 ratio.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomisation stratified by:BMI at randomisation(<30/≥30 kg/m2),HbA1c at screening (<8.5%/ ≥8.5%);geographical region(North America including Australia and New Zealand,Latin America,Europe,Africa,Asia);renal function at screening (normal:eGFR ≥90 mL/min, mild impairment:60 mL/min ≤ eGFR ≤89 mL/min, moderate impairment:30 mL/min ≤ eGFR≤59 mL/min).

Reporting Groups

	Description
Placebo	Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily)
Empagliflozin 10 mg	Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)
Empagliflozin 25 mg	Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)

Participant Flow for 2 periods

Period 1: Discontinuation From Treatment

	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg
STARTED	2337 ^[1]	2347 ^[1]	2344 ^[1]
COMPLETED	1650 ^[2]	1790 ^[2]	1800 ^[2]
NOT COMPLETED	687	557	544
Study drug stopped, reason missing	5	3	4
Not treated	4	2	2
Lack of Efficacy	11	1	0
Non compliant with protocol	15	15	12
Lost to Follow-up	15	9	6
Refusal to continue, not due to AE	172	118	122
Other than those specified	162	142	125
Adverse Event	303	267	273

^[1]	Randomised
^[2]	Not prematurely discontinued from trial medication

Period 2: Discontinuation From Study (Treated Set)

	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg
STARTED	2333	2345	2342
Final Vital Status (VS) Available	2316	2324	2327
COMPLETED	2266 ^[1]	2264 ^[1]	2279 ^[1]
NOT COMPLETED	67	81	63
Consent withdrawn: Final VS available	23	35	25
Consent withdrawn:Final VS not available	8	6	5
Site closure: Final VS available	20	21	19
Site closure:Final VS not available (NA)	5	9	7
Lost to FU for 3PMACE:Final VS available	7	6	5
Lost to FU for 3P-MACE:Final VS NA	4	4	2

^[1]	Completed the trial or died

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated set (TS): Consists of all randomised patients who received at least 1 dose of study medication. Patients were assigned to treatment groups according to the randomisation scheme.

Reporting Groups

	Description
Placebo	Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily)
Empagliflozin 10 mg	Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)
Empagliflozin 25 mg	Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)
Total	Total of all reporting groups

Baseline Measures

	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	Total
Overall Participants Analyzed [Units: Participants]	2333	2345	2342	7020

Age [Units: Years] Mean (Standard Deviation)	63.2 (8.8)	63.0 (8.6)	63.2 (8.6)	63.1 (8.6)

Gender [Units: Participants]
Female	653	692	659	2004
Male	1680	1653	1683	5016

Outcome Measures

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1. Primary:

Time to the First Occurrence of Any of the Following Adjudicated Components of the Primary Composite Endpoint (3-point MACE): CV Death (Including Fatal Stroke and Fatal MI), Non-fatal MI (Excluding Silent MI), and Non-fatal Stroke. [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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2. Secondary:

Percentage of Participants With the Composite of All Events Adjudicated (4-point MACE): CV Death (Including Fatal Stroke and Fatal MI), Non-fatal MI (Excluding Silent MI), Non-fatal Stroke and Hospitalization for Unstable Angina Pectoris [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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3. Secondary:

Percentage of Participants With Silent MI [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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4. Secondary:

Percentage of Participants With Heart Failure Requiring Hospitalisation (Adjudicated) [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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5. Secondary:

Percentage of Participants With New Onset Albuminuria [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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6. Secondary:

Percentage of Participants With New Onset Macroalbuminuria [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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7. Secondary:

Percentage of Participants With the Composite Microvascular Outcome [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
2 sets of duplicates(4 patients(pts)) were counted only once.652 sites were initiated and 611 enrolled.One site transferred all pts to other sites.27 pts randomised and 13 pts screened were excluded from analyses due to serious non-compliance

More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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

Results Point of Contact:

Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
phone: 800-243-0127 ext +1
e-mail: clintriage.rdg@boehringer-ingelheim.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

Zinman B, Inzucchi SE, Lachin JM, Wanner C, Ferrari R, Fitchett D, Bluhmki E, Hantel S, Kempthorne-Rawson J, Newman J, Johansen OE, Woerle HJ, Broedl UC. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014 Jun 19;13:102. doi: 10.1186/1475-2840-13-102.

Responsible Party:	Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT01131676 History of Changes
Other Study ID Numbers:	1245.25 2009-016178-33 ( EudraCT Number: EudraCT )
Study First Received:	May 26, 2010
Results First Received:	April 7, 2016
Last Updated:	April 7, 2016

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