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Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure (MEASURE-HF)

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: NCT02917031
Recruitment Status : Active, not recruiting
First Posted : September 28, 2016
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE September 9, 2016
First Posted Date  ICMJE September 28, 2016
Last Update Posted Date April 22, 2019
Actual Study Start Date  ICMJE January 10, 2017
Estimated Primary Completion Date August 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2016)
The change in LVEDV index measured by MRI from baseline to Week 24 [ Time Frame: From baseline to Week 24 ]
To exclude an increase in left ventricular end diastolic volume (LVEDV) index of greater than 10% in patients with Type 2 Diabetes Mellitus (T2DM) and Heart Failure (HF) treated with saxagliptin for 24 weeks, compared to placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02917031 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2016)
  • The change in LVESV index measured by MRI from baseline to Week 24 [ Time Frame: From baseline to Week 24 ]
    Evaluate the effects of saxagliptin compared to placebo on left ventricular end systolic volume (LVESV) index after 24 weeks in patients with T2DM and HF
  • The change in LVEF measured by MRI from baseline to Week 24 [ Time Frame: From baseline to Week 24 ]
    Evaluate the effects of saxagliptin compared to placebo on left ventricular ejection fraction (LVEF) after 24 weeks in patients with T2DM and HF
  • The change in LVM measured by MRI from baseline to Week 24 [ Time Frame: From baseline to Week 24 ]
    Evaluate the effects of saxagliptin compared to placebo on left ventricular mass (LVM) after 24 weeks in patients with T2DM and HF
  • The change from baseline in NT-proBNP after 24 weeks of treatment [ Time Frame: From baseline to Week 24 ]
    Evaluate the effects of saxagliptin compared to placebo on N-terminal prohormone of brain natriuretic peptide (NT-proBNP) after 24 weeks of treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure
Official Title  ICMJE A 24-Week, Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Investigate the Effects of Saxagliptin and Sitagliptin in Patients With Type 2 Diabetes Mellitus and Heart Failure
Brief Summary This is a 24 week, multicenter, randomized, double-blind, parallel group, placebo-controlled study to investigate the effects of saxagliptin and sitagliptin on cardiac dimensions and function in patients with type 2 diabetes (T2DM) mellitus and heart failure (HF).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 2 Diabetes Mellitus
  • Heart Failure
Intervention  ICMJE
  • Drug: Saxagliptin
    5 mg or 2.5 mg, plain, yellow, biconvex, round, film-coated tablet
    Other Name: Onglyza TM
  • Drug: Sitagliptin
    50 mg or 100 mg, gray capsule
    Other Name: Januvia®
  • Drug: Placebo to match saxagliptin
    2.5 mg or 5 mg, plain, yellow, biconvex, round, film-coated tablet
  • Drug: Placebo to match sitagliptin
    50 mg or 100 mg, gray capsule
Study Arms  ICMJE
  • Active Comparator: Saxagliptin
    one tablet of saxagliptin 5 mg or 2.5 mg + one placebo capsule matching sitagliptin
    Interventions:
    • Drug: Saxagliptin
    • Drug: Placebo to match sitagliptin
  • Active Comparator: Sitagliptin
    one capsule of sitagliptin 100 mg or 50 mg + one placebo tablet matching saxagliptin
    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo to match saxagliptin
  • Placebo Comparator: Placebo
    one placebo tablet matching saxagliptin + one placebo capsule matching sitagliptin
    Interventions:
    • Drug: Placebo to match saxagliptin
    • Drug: Placebo to match sitagliptin
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 19, 2019)
348
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2016)
330
Estimated Study Completion Date  ICMJE August 23, 2019
Estimated Primary Completion Date August 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  1. Provision of informed consent prior to any study specific procedure (Pre-screening ICF and Informed Consent collected at screening)
  2. Male or female, aged ≥18 years at the time of consent
  3. Documented, controlled T2DM, as defined by:

    • Diagnosis of Type 2 DM based on current ADA guidelines (Appendix C) Treatment with stable doses of antidiabetic medications that have not increased or decreased for ≥8 weeks before screening
    • For patients taking insulin, the investigator must query the patient at prescreening or screening regarding his/her usual total daily insulin dose (all types combined) during the previous 8 weeks. Insulin dosages during pre-screening and screening should not vary by more than ±20% on more than two occasions
    • Dosage reductions of insulin and sulfonylurea agents may be considered at randomization to minimize the possibility of hypoglycemia

      • Any reductions in the dosage of insulin and sulfonylurea agents will be at the discretion of the investigator
      • For patients treated with insulin, consider a reduction in dose of 20% at randomization
      • For patients receiving sulfonylurea agents, consider a reduction in dose of 50% or discontinue if on a dosage that is considered low at randomization
  4. HFrEF demonstrated by all 3 of the following criteria:

    • History of HF and LVEF ≤45% within the last 6 months (echocardiogram, MRI, left ventriculography, or other accepted methodology). Patients without a recent assessment of LV function will undergo a local echocardiogram at the time of screening to determine ejection fraction
    • Elevated NT-proBNP (>300 pg/mL) during screening
    • Patients should receive background standard of care for HFrEF and be treated according to locally recognized guidelines as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated. Therapy should have been individually optimized and stable for >or = 4 weeks (this does not apply to diuretics-see NB below) before screening visit and include (unless contraindicated or not tolerated):
    • an ACE inhibitor, or ARB, or sacubitril/valsartan
    • and
    • a beta-blocker
    • and
    • if considered appropriate by the patient's treating physician; a mineralocorticoid receptor antagonist (MRA)
    • NB: Most patients with heart failure require treatment with a diuretic to control sodium and water retention leading to volume overload. It is recognized that diuretic dosing may be titrated to symptoms, signs, weight, and other information and may thus vary. Each patient should, however, be treated with a diuretic regimen aimed at achieving optimal fluid/volume status for that individual
  5. Stable HF, with no evidence of volume overload (no rales, jugular venous distention, peripheral edema) at screening
  6. Women of childbearing potential (WOCBP):

    • Must be using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product
    • Must have a negative serum or urine pregnancy test within 72 hours prior to the start of investigational product
    • Must not be breastfeeding.

EXCLUSION CRITERIA:

  1. MRI contraindications: all implanted defibrillators; implanted pacemakers and other devices/implants that in the judgment of the investigator preclude an MRI evaluation
  2. Patients with atrial fibrillation/flutter, or any rhythm that would impact on MRI imaging quality would be excluded. Patients with a prior history of atrial fibrillation or paroxysmal atrial fibrillation may be eligible for entry into the study based on the investigator's judgment related to the frequency of AF events and the patient's overall condition
  3. Body mass index >45 kg/m2 or any condition, including, but not limited to known claustrophobia, that may preclude the ability to perform an MRI scan of acceptable quality, or unwillingness to undergo MRI imaging
  4. Receiving incretin therapy (DPP4 inhibitors, GLP-1 mimetics), or having received incretin therapy within the previous 8 weeks of randomization
  5. Receiving therapy with a TZD or having received TZD therapy within the previous 8 weeks of randomization
  6. Type 1 diabetes mellitus
  7. History of unstable or rapidly progressing renal disease
  8. A central lab eGFR value <30 mL/min/1.73 m2 on pre-screening or screening
  9. New York Heart Association (NYHA) Class IV HF
  10. Myocardial infarction, stroke, transient ischemic attack, or coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) within the past 3 months of screening
  11. Inoperable aortic or mitral valvular heart disease. Recent (within 3 months) or planned valvular heart procedure
  12. Heart failure secondary to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, and hypertrophic obstructive cardiomyopathy
  13. Previous cardiac transplantation or transplantation indicated or expected within 6 months of randomization
  14. Contraindications to saxagliptin therapy as outlined in the saxagliptin Investigator's Brochure, or to sitagliptin therapy as outlined in the sitagliptin prescribing information
  15. Current treatment with strong cytochrome P450 (CYP) 3A4/5 inhibitors
  16. Involvement in the planning and/or conduct of the study (applies to both AZ staff and/or staff at the study site)
  17. Previous enrollment which disqualifies patient from re-enrollment based on the rules in Section 4.1 of the protocol, or previous randomization in the study
  18. Participation in another clinical study with an investigational product during the last 30 days
  19. Patients either employed by or immediate relatives of the Sponsor
  20. Known human immunodeficiency virus (HIV) infection
  21. Severe hepatic disease, including chronic active hepatitis. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for hepatitis B viral antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody; or aspartate transaminase (AST) or alanine transaminase (ALT) >3X the upper limit of normal; or total bilirubin (TB) >2 mg/dL
  22. Active malignancy requiring treatment at the time of Visit 1(with the exception of successfully treated basal cell or treated squamous cell carcinoma).
  23. Pregnant, positive pregnancy test, planning to become pregnant during clinical trial or breast feeding
  24. History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study
  25. Unable or unwilling to provide written informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (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 Bulgaria,   Canada,   Chile,   Hungary,   Korea, Republic of,   Romania,   Russian Federation,   Thailand,   Ukraine,   United States
Removed Location Countries Spain,   Taiwan
 
Administrative Information
NCT Number  ICMJE NCT02917031
Other Study ID Numbers  ICMJE D1680C00016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date April 2019

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