Saxagliptin and Cardiac Structure and Function

NCT02481479 | Completed Phase 4

• 1 other identifier: 14-267
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes is associated with a substantially increased risk of heart failure, which is associated with substantial morbidity and mortality. Despite the development of new therapeutic strategies to improve glycemic control, recent clinical data from the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study observed an unexpected finding of an excess of adjudicated heart failure hospitalizations. This excess occurred in the setting of pre-existing heart failure (HF) hospitalization and in those with elevated biomarkers for heart failure such as N terminal pro Brain type natriuretic peptide (NT-pro BNP). A wealth of preclinical data did not suggest a mechanistic basis for an excess of heart failure events, however these preclinical studies primarily focused upon prevention based strategies as opposed to regression studies once established heart failure was present. This proposal seeks to understand if and how dipeptidyl peptidase-4 inhibitors (DPP4i,specifically saxagliptin) may influence the development of heart failure, by evaluating changes in cardiac structure and function using cardiac magnetic resonance imaging (MRI).

Conditions

Diabetes Mellitus, Non-Insulin-Dependent; Heart Failure

Outcome Measures

Primary Outcomes (1)

• The change in LVEF from baseline to 6 months

  assess LVEF at baseline and at 6 months following treatment. CMR based LVEF assessment using Cvi 42.

  baseline, 6 months

Secondary Outcomes (3)

• The change in E/e' from baseline to 6 months

  baseline, 6 months

• change in class indicators of signs and symptoms of heart failure at each visit

  baseline, 6 months

• Change in log-scale in NT-pro BNP

  baseline, 6 months

Study Arms (1)

Single group -Paired comparison

OTHER

Saxagliptin 2.5mg or 5mg od

Drug: Saxagliptin

Interventions

saxagliptin DRUG

Eligible patients will undergo baseline CMR, commence treatment and then after 6 months undergo repeat CMR

Also known as: Onglyza

Single group -Paired comparison

Eligibility Criteria

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

You may qualify if:

• Adult (≥18 years old) men or women with type 2 diabetes diagnosed for ≥ 6 months
• HbA1c 7.5 - 9.5%
• Receiving background therapy with metformin (additional anti-hyperglycemic agents are permitted)
• Clinical decision to initiate saxagliptin to improve glycemic control, as per treating physician

You may not qualify if:

• GLP-1 receptor agonist or DPP4 inhibitor treatment within the past 6 months, or known intolerance
• eGFR \<30
• Baseline LVEF \<40%
• NYHA Class III-IV or recent hospitalization for decompensated HF (\<3 months)
• Unstable coronary syndromes or recent revascularization within the past 3 months, or planned revascularization in the next 6 months
• Significant (moderate or severe, or symptomatic) valvular disease
• Pregnancy/childbearing potential
• Routine contraindications to CMR Subjects who drop out from the study will have a repeat CMR examination as soon as possible after drug discontinuation.

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Heart Failure

Interventions

saxagliptin

Condition Hierarchy (Ancestors)

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

Study Officials

• Subodh Verma, MD

  Professor of Surgery

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 25, 2015
• Study Start: June 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: March 30, 2020

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: 1 yr
• Access Criteria: contact study PI

Locations

CA (1)