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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

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).

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Heart Failure Drug: Saxagliptin Drug: Sitagliptin Drug: Placebo to match saxagliptin Drug: Placebo to match sitagliptin Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 348 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 10, 2017
Estimated Primary Completion Date : August 23, 2019
Estimated Study Completion Date : August 23, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Saxagliptin
one tablet of saxagliptin 5 mg or 2.5 mg + one placebo capsule matching sitagliptin
Drug: Saxagliptin
5 mg or 2.5 mg, plain, yellow, biconvex, round, film-coated tablet
Other Name: Onglyza TM

Drug: Placebo to match sitagliptin
50 mg or 100 mg, gray capsule

Active Comparator: Sitagliptin
one capsule of sitagliptin 100 mg or 50 mg + one placebo tablet matching saxagliptin
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

Placebo Comparator: Placebo
one placebo tablet matching saxagliptin + one placebo capsule matching sitagliptin
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02917031


  Show 71 Study Locations
Sponsors and Collaborators
AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02917031     History of Changes
Other Study ID Numbers: D1680C00016
First Posted: September 28, 2016    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Type 2 Diabetes Mellitus
Heart Failure
Saxagliptin
Sitagliptin

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Heart Failure
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Sitagliptin Phosphate
Saxagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action