Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure

NCT02917031 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: D1680C00016
• Study Type: interventional
• Target: 348
• Locations: 10 countries
• Sites: 74

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).

Conditions

Type 2 Diabetes Mellitus; Heart Failure

Keywords

Type 2 Diabetes Mellitus; Heart Failure; Saxagliptin; Sitagliptin

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) Index Measured by Magnetic Resonance Imaging (MRI) at 24 Weeks

  MRI was performed to evaluate LVEDV at baseline and Visit 10 (Week 24). Evaluated to exclude an increase in left ventricular end diastolic volume (LVEDV) index of greater than 10% of the overall baseline value (noninferiority margin) in patients with T2DM and HF treated with saxagliptin for 24 weeks, compared to placebo. Baseline is last assessment on or before the date of first dose.

  Baseline to 24 weeks

Secondary Outcomes (5)

• Change From Baseline in Left Ventricular End Systolic Volume (LVESV) Index, Measured by MRI at 24 Weeks.

  Baseline to week 24

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Measured by MRI at 24 Weeks.

  Baseline to week 24

• Change From Baseline in Left Ventricular Mass (LVM) Measured by MRI at 24 Weeks.

  At 24 week

• Change From Baseline in NT-proBNP After 24 Weeks of Treatment

  Baseline to Week 28 (End of Study visit [EoS])

• Number of Participants With Adverse Events

  From screening (Days -28 to -1) until Week 28 (follow-up visit)

Study Arms (3)

Saxagliptin

ACTIVE COMPARATOR

one tablet of saxagliptin 5 mg or 2.5 mg + one placebo capsule matching sitagliptin

Drug: Saxagliptin; Drug: Placebo to match sitagliptin

Sitagliptin

ACTIVE COMPARATOR

one capsule of sitagliptin 100 mg or 50 mg + one placebo tablet matching saxagliptin

Drug: Sitagliptin; Drug: Placebo to match saxagliptin

Placebo

PLACEBO COMPARATOR

one placebo tablet matching saxagliptin + one placebo capsule matching sitagliptin

Drug: Placebo to match saxagliptin; Drug: Placebo to match sitagliptin

Interventions

Saxagliptin DRUG

5 mg or 2.5 mg, plain, yellow, biconvex, round, film-coated tablet

Also known as: Onglyza TM

Saxagliptin

Sitagliptin DRUG

50 mg or 100 mg, gray capsule

Also known as: Januvia®

Sitagliptin

Placebo to match saxagliptin DRUG

2.5 mg or 5 mg, plain, yellow, biconvex, round, film-coated tablet

Placebo; Sitagliptin

Placebo to match sitagliptin DRUG

50 mg or 100 mg, gray capsule

Placebo; Saxagliptin

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedure (Pre-screening ICF and Informed Consent collected at screening)
• Male or female, aged ≥18 years at the time of consent
• 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
• 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

You may not qualify if:

• MRI contraindications: all implanted defibrillators; implanted pacemakers and other devices/implants that in the judgment of the investigator preclude an MRI evaluation
• 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
• 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
• Receiving incretin therapy (DPP4 inhibitors, GLP-1 mimetics), or having received incretin therapy within the previous 8 weeks of randomization
• Receiving therapy with a TZD or having received TZD therapy within the previous 8 weeks of randomization
• Type 1 diabetes mellitus
• History of unstable or rapidly progressing renal disease
• A central lab eGFR value \<30 mL/min/1.73 m2 on pre-screening or screening
• New York Heart Association (NYHA) Class IV HF
• 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
• Inoperable aortic or mitral valvular heart disease. Recent (within 3 months) or planned valvular heart procedure
• Heart failure secondary to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, and hypertrophic obstructive cardiomyopathy
• Previous cardiac transplantation or transplantation indicated or expected within 6 months of randomization
• Contraindications to saxagliptin therapy as outlined in the saxagliptin Investigator's Brochure, or to sitagliptin therapy as outlined in the sitagliptin prescribing information
• Current treatment with strong cytochrome P450 (CYP) 3A4/5 inhibitors

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (74)

Research Site

Torrance, California, 90502, United States

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Upland, California, 91786, United States

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Miami, Florida, 33133, United States

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Ormond Beach, Florida, 32174, United States

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Chicago, Illinois, 60610, United States

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The Bronx, New York, 10455, United States

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The Bronx, New York, 10459, United States

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Sayre, Pennsylvania, 18840, United States

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Spartanburg, South Carolina, 29302, United States

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Houston, Texas, 77089, United States

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Milwaukee, Wisconsin, 64111, United States

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Sofia, 1142, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1618, Bulgaria

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Sofia, 1784, Bulgaria

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Chicoutimi, Quebec, G7H 7K9, Canada

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Santiago, 8207257, Chile

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Santiago, 8360160, Chile

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Santiago, 8380453, Chile

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Santiago, 8910259, Chile

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Talcahuano, 4270918, Chile

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Viña del Mar, 2520997, Chile

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Balatonfüred, 8230, Hungary

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Budapest, 1122, Hungary

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Budapest, 1134, Hungary

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Budapest, 1171, Hungary

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Debrecen, 4032, Hungary

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Hajdúszoboszló, 4200, Hungary

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Kecskemét, 6000, Hungary

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Kisvárda, 4600, Hungary

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Nyíregyháza, 4400, Hungary

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Orosháza, 5900, Hungary

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Pécs, 7623, Hungary

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Székesfehérvár, 8000, Hungary

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Brasov, 500365, Romania

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Iași, 700304, Romania

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Iași, 700515, Romania

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Izhevsk, 426035, Russia

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Kemerovo, 650002, Russia

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Moscow, 109263, Russia

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Moscow, 115516, Russia

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Moscow, 121551, Russia

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Nizhny Novgorod, 603018, Russia

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Novosibirsk, 630055, Russia

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Novosibirsk, 630087, Russia

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Novosibirsk, 630089, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 197341, Russia

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Saint Petersburg, 199226, Russia

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Tomsk, 634012, Russia

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Tomsk, 634050, Russia

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Yaroslavl, 150062, Russia

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Busan, 49241, South Korea

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Daejeon, 35015, South Korea

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Gwangju, 61469, South Korea

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Hwaseong-si, 18450, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Wŏnju, 26426, South Korea

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkoknoi, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Khon Kaen, 40002, Thailand

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Ivano-Frankivsk, 76005, Ukraine

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Ivano-Frankivsk, 76018, Ukraine

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Kyiv, 02091, Ukraine

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Kyiv, 02660, Ukraine

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Kyiv, 03680, Ukraine

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Lviv, 79015, Ukraine

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Rivne, 33007, Ukraine

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Related Publications (1)

• Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.

  PMID: 34693515 DERIVED

Related Links

• redacted Protocol (CSP)
• Statistical Analysis Plan (SAP)

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Heart Failure

Interventions

saxagliptin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: AstraZeneca R&D
• Organization: AstraZeneca R&D

clinicaltrialtransparency@astrazeneca.com

+46 766 346712

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 28, 2016
• Study Start: January 10, 2017
• Primary Completion: August 23, 2019
• Study Completion: August 23, 2019
• Last Updated: November 8, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-10

Locations

TH (5); BU (5); CL (6); CA (1); RU (15); UA (7); RO (3); KR (9); HU (12); US (11)