Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus

Tracking Information
First Submitted Date ICMJE	June 10, 2010
First Posted Date ICMJE	June 15, 2010
Results First Submitted Date	April 13, 2018
Results First Posted Date	August 8, 2018
Last Update Posted Date	August 8, 2018
Actual Study Start Date ICMJE	June 18, 2010
Actual Primary Completion Date	April 21, 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 13, 2018)	Primary Efficacy Outcome MACE Events [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]The primary efficacy outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. The number of participants who had an event is reported in the results. The primary efficacy endpoint is the same as the primary safety endpoint, and the statistical analysis tests the superiority of exenatide against the placebo.; Primary Safety Outcome MACE Events [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]The primary safety outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. The number of participants who had an event is reported in the results. The primary safety endpoint is the same as the primary efficacy endpoints, and the statistical analysis tests the non-inferiority of exenatide against placebo.
Original Primary Outcome Measures ICMJE; (submitted: June 14, 2010)	Time to first confirmed cardiovascular event in the primary composite cardiovascular endpoint. [ Time Frame: 5.5 years (average) ]
Change History	Complete list of historical versions of study NCT01144338 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 13, 2018)	Secondary Efficacy Outcome All-Cause Mortality [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]The secondary efficacy outcome variable is defined as the all-cause mortality (deaths). The number of participants who had an event is reported in the results.; Secondary Efficacy Outcome CV Death [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]Component of the primary efficacy outcome: cardiovascular death. The number of participants who had an event is reported in the results.; Secondary Efficacy Outcome MI [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]Component of primary efficacy outcome: fatal or non-fatal MI. The number of participants who had an event is reported in the results.; Secondary Efficacy Outcome Stroke [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]Component of primary efficacy outcome: fatal or non-fatal stroke. The number of participants who had an event is reported in the results.; Secondary Efficacy Outcome Hospitalization for ACS [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]The secondary efficacy outcome variable is defined as hospitalization for acute coronary syndrome. The number of participants who had an event is reported in the results.; Secondary Efficacy Outcome Hospitalization for HF [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ]The secondary efficacy outcome variable is defined as hospitalization for heart failure. The number of participants who had an event is reported in the results.
Original Secondary Outcome Measures ICMJE; (submitted: June 14, 2010)	Time to all-cause mortality [ Time Frame: 5.5 years (average) ]; Time to first confirmed cardiovascular event for each component of the primary composite endpoint [ Time Frame: 5.5 years (average) ]; Time to hospitalization for acute coronary syndrome [ Time Frame: 5.5 years (average) ]; Time to hospitalization for heart failure [ Time Frame: 5.5 years (average) ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus
Official Title ICMJE	Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL). A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus.
Brief Summary	This study will compare the impact of including exenatide once weekly in addition to usual care vs. usual care without exenatide on major cardiovascular outcomes as measured by the primary composite endpoint of cardiovascular-related death, nonfatal myocardial infarction (MI), or nonfatal stroke.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Type 2 Diabetes Mellitus
Intervention ICMJE	Drug: Exenatide Once Weekly Subcutaneous injection, 2 mg, administered once weekly.; Drug: Placebo Subcutaneous injection, matching volume of placebo, administered once weekly.
Study Arms	Experimental: Exenatide Once Weekly Intervention: Drug: Exenatide Once Weekly; Placebo Comparator: Placebo Intervention: Drug: Placebo
Publications *	Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, Chan JC, Choi J, Gustavson SM, Iqbal N, Maggioni AP, Marso SP, Öhman P, Pagidipati NJ, Poulter N, Ramachandran A, Zinman B, Hernandez AF; EXSCEL Study Group. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2017 Sep 28;377(13):1228-1239. doi: 10.1056/NEJMoa1612917. Epub 2017 Sep 14.; Mentz RJ, Bethel MA, Gustavson S, Thompson VP, Pagidipati NJ, Buse JB, Chan JC, Iqbal N, Maggioni AP, Marso SP, Ohman P, Poulter N, Ramachandran A, Zinman B, Hernandez AF, Holman RR. Baseline characteristics of patients enrolled in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Am Heart J. 2017 May;187:1-9. doi: 10.1016/j.ahj.2017.02.005. Epub 2017 Feb 12.; Holman RR, Bethel MA, George J, Sourij H, Doran Z, Keenan J, Khurmi NS, Mentz RJ, Oulhaj A, Buse JB, Chan JC, Iqbal N, Kundu S, Maggioni AP, Marso SP, Öhman P, Pencina MJ, Poulter N, Porter LE, Ramachandran A, Zinman B, Hernandez AF. Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. Am Heart J. 2016 Apr;174:103-10. doi: 10.1016/j.ahj.2015.12.009. Epub 2015 Dec 21.; Gaebler JA, Soto-Campos G, Alperin P, Cohen M, Blickensderfer A, Wintle M, Maggs D, Hoogwerf B, Han J, Pencek R, Peskin B. Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis. Vasc Health Risk Manag. 2012;8:255-64. doi: 10.2147/VHRM.S28744. Epub 2012 Apr 23.
* 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: August 31, 2017)	14752
Original Estimated Enrollment ICMJE; (submitted: June 14, 2010)	9500
Actual Study Completion Date	April 24, 2017
Actual Primary Completion Date	April 21, 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patient has type 2 diabetes mellitus; Patient has an HbA1c of ≥ 6.5 % and ≤ 10.0% and is currently using one of the following treatment regimens: A) Treatment with 0-3 oral antihyperglycemic agents B) Insulin therapy, either alone or in combination with up to two oral agents; Female patients must not be breast feeding and agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant. Exclusion Criteria: Patient has a diagnosis of type 1 diabetes mellitus, or a history of ketoacidosis.; Patient has ever been treated with an approved or investigational GLP-1 receptor agonist.; Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial.; Patient has a planned or anticipated revascularization procedure.; Pregnancy or planned pregnancy during the trial period.; Patient has end-stage renal disease or an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m2.; Patient has a history of gastroparesis or pancreatitis.; Personal or family history of medullary thyroid cancer or MEN2 (Multiple EndocrineNeoplasia Type 2) or calcitonin level of >40 ng/L at baseline.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 130 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Germany, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Philippines, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Removed Location Countries	Czech Republic, France, India, Peru
Administrative Information
NCT Number ICMJE	NCT01144338
Other Study ID Numbers ICMJE	D5551C00003; MB001-002 ( Other Identifier: Bristol Myers Squibb ); BCB109 ( Other Identifier: Bristol-Myers Squibb )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	AstraZeneca
Study Sponsor ICMJE	AstraZeneca
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Stephanie Gustavson, PhD AstraZeneca Study Director: Group Director Global Clinical Research Bristol-Myers Squibb
PRS Account	AstraZeneca
Verification Date	July 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP