Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01131676
Recruitment Status : Completed
First Posted : May 27, 2010
Results First Posted : May 16, 2016
Last Update Posted : May 16, 2016
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE May 26, 2010
First Posted Date  ICMJE May 27, 2010
Results First Submitted Date  ICMJE April 7, 2016
Results First Posted Date  ICMJE May 16, 2016
Last Update Posted Date May 16, 2016
Study Start Date  ICMJE July 2010
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 7, 2016)		 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 ]
Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI (excluding silent MI), and non-fatal stroke. Percentage of patients with the event are presented.
Original Primary Outcome Measures  ICMJE
 (submitted: May 26, 2010)		 The primary endpoint is time to the first occurrence of any of the following adjudicated components of the primary composite endpoint: cardiovascular death (including fatal stroke and fatal myocardial infarction(MI)), non-fatal MI and non-fatal stroke. [ Time Frame: 4 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2016)
  • 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 ]
    The composite of all events adjudicated (4-point MACE): cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris.This is a key secondary endpoint of the trial. Percentage of patients with the event are presented.
  • Percentage of Participants With Silent MI [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]
    Silent MI; defined as presence in the ECG of:
    • Any Q-wave in leads V2-V3 ≥0.02 seconds or QS complex in leads V2 and V3
    • Q-wave ≥0.03 seconds and ≥0.1 mV deep or QS complex in leads I, II, aVL, aVF, or V4-V6 in any two leads of a contiguous lead grouping (I, aVL, V6; V4-V6; II, III, and aVF)
    • R-wave ≥0.04 seconds in V1-V2 and R/S ≥1 with a concordant positive T-wave in the absence of a conduction defect.
    It was also required that there had been no adjudicated and confirmed event of either acute MI, hospitalisation for unstable angina, coronary revascularisation procedures or stent thrombosis following randomisation up to and including the date of the specified ECG measurement. Percentage of patients with the event are presented.
  • Percentage of Participants With Heart Failure Requiring Hospitalisation (Adjudicated) [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]
    Heart failure requiring hospitalisation (adjudicated). Percentage of patients with the event are presented.
  • Percentage of Participants With New Onset Albuminuria [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]
    New onset albuminuria defined as urine albumin / creatinine ratio (UACR) ≥30 mg/g. Percentage of patients with the event are presented.
  • Percentage of Participants With New Onset Macroalbuminuria [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]
    New onset macroalbuminuria defined as UACR >300 mg/g. Percentage of patients with the event are presented.
  • Percentage of Participants With the Composite Microvascular Outcome [ Time Frame: From randomisation to individual end of observation, up to 4.6 years ]
    Composite microvascular outcome defined as:
    • Initiation of retinal photocoagulation
    • Vitreous haemorrhage
    • Diabetes-related blindness, or
    • New or worsening nephropathy defined as:
      • New onset of macroalbuminuria; or
      • Doubling of serum creatinine level accompanied by an eGFR (based on modification of diet in renal disease (MDRD) formula) ≤45 mL/min/1.73m2; or
      • Initiation of continuous renal replacement therapy, or
      • Death due to renal disease. Percentage of patients with the event are presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2010)
  • The composite of all events adjudicated: cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatalmyocardial infarctionI, non-fatal stroke and hospitalization for unstable angina pectoris. [ Time Frame: 4 years ]
  • To determine the incidence of microalbuminuria and the progression of microalbuminuria to macroalbuminuria from baseline to end of trial. [ Time Frame: 4 years ]
  • To determine the incidence of silent MI [ Time Frame: 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME).
Official Title  ICMJE A Phase III, Multicentre, International, Randomised, Parallel Group, Double Blind Cardiovascular Safety Study of BI 10773 (10 mg and 25 mg Administered Orally Once Daily) Compared to Usual Care in Type 2 Diabetes Mellitus Patients With Increased Cardiovascular Risk
Brief Summary The aim of the present study is to investigate the safety of BI 10773 treatment in patients with Type 2 Diabetes Mellitus and high cardiovascular risk.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: BI 10773 low dose
    BI 10773 tablets once daily
  • Drug: Placebo BI 10773 high dose
    Placebo tablets identical to BI 10773
  • Drug: BI 10773 high dose
    BI 10773 tablets once daily
  • Drug: Placebo BI 10773 low dose
    Placebo tablets identical to BI 10773
Study Arms  ICMJE
  • Experimental: BI 10773 low dose
    BI 10773 tablets once daily
    Interventions:
    • Drug: BI 10773 low dose
    • Drug: Placebo BI 10773 high dose
  • Experimental: BI 10773 high dose
    BI 10773 tablets once daily
    Interventions:
    • Drug: BI 10773 high dose
    • Drug: Placebo BI 10773 low dose
  • Placebo Comparator: Placebo
    Placebo tablets matching BI 10773
    Interventions:
    • Drug: Placebo BI 10773 high dose
    • Drug: Placebo BI 10773 low dose
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 11, 2016)		 7064
Original Estimated Enrollment  ICMJE
 (submitted: May 26, 2010)		 4000
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Diagnosis of type 2 diabetes mellitus prior to informed consent
  2. Male or female patients on diet and exercise regimen who are drug naive or pre treated with any background therapy. Antidiabetic therapy has to be unchanged for 12 weeks prior to randomization.
  3. Glycosylated haemoglobin (HbA1c) of >= 7.0% and <=10% for patients on background therapy or HbA1c >= 7.0% and <= 9.0% for drug naive patients
  4. Age >= 18 years
  5. Body Mass index <= 45 at Visit 1
  6. Signed and dated informed consent
  7. High cardiovascular risk

Exclusion criteria:

  1. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
  2. Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase ALT or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at screening and/or run in.
  3. Planned cardiac surgery or angioplasty within 3 months
  4. Impaired renal function, defined as Glomerular Filtration Rate <30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) during screening or run in.
  5. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
  6. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia)
  7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
  8. Contraindications to background therapy according to the local label
  9. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight
  10. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except type 2 diabetes mellitus

  11. Pre-menopausal women (last menstruation <+ 1 year prior to informed consent) who:

    • are nursing or pregnant or
    • are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method and vasectomised partner
  12. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
  13. Participation in another trial with an investigational drug within 30 days prior to informed consent
  14. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
  15. Acute coronary syndrome, stroke or TIA within 2 months prior to informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Colombia,   Croatia,   Czech Republic,   Denmark,   Estonia,   France,   Georgia,   Greece,   Hong Kong,   Hungary,   India,   Indonesia,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Norway,   Peru,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   South Africa,   Spain,   Sri Lanka,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries Egypt,   El Salvador,   Germany,   Lebanon,   Lithuania,   Saudi Arabia,   Switzerland,   United Arab Emirates
 
Administrative Information
NCT Number  ICMJE NCT01131676
Other Study ID Numbers  ICMJE 1245.25
2009-016178-33 ( EudraCT Number: EudraCT )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Eli Lilly and Company
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP