ERtugliflozin triAl in DIabetes With Preserved or Reduced ejeCtion FrAcTion mEchanistic Evaluation in Heart Failure

• Status: Unknown status
• Trial end date: 2021-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to elucidate the mechanisms whereby the SGLT2i "ertugliflozin" modifies cardiorenal interactions that regulate fluid volume and neurohormonal activation in patients with type 2 diabetes and heart failure (T2D-HF).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborators: Merck Sharp & Dohme Corp.; Toronto General Hospital; University Medical Center Groningen; University of Toronto
• Treatments: Ertugliflozin

Criteria

Inclusion Criteria:

1. Male or female subjects diagnosed with T2D ≥12 months prior to informed consent;

2. eGFR ≥30 ml/min/1.73m2;

3. Age >18 years;

4. HbA1c 6.5%-10.5%;

5. Body Mass Index (BMI) 18.5-45.0 kg/m2;

6. Blood pressure ≤160/110 and ≥90/60 at screening,

7. Heart failure with New York Heart Association (NYHA) class 2-3 symptoms and ejection fraction ≥20%

8. Stable dose of maximally tolerated ACE inhibitor, angiotensin receptor blocker or renin inhibitor for at least 30 days

9. Stable diuretic dose for at least 30 days at the time of baseline physiological assessment

10. BNP levels at baseline ≥100 pg/ml (no atrial fibrillation), ≥200 pg/ml if in atrial fibrillation

Exclusion Criteria:

1. Type 1 Diabetes;

2. Leukocyte and/or nitrite positive urinalysis that is untreated;

3. Severe hypoglycaemia within 2 months prior to screening;

4. History of brittle diabetes or hypoglycaemia unawareness based on investigator judgement;

5. Unstable coronary artery disease with acute coronary syndrome, percutaneous intervention or bypass surgery within 3 months;

6. Clinically significant valvular disease;

7. Congestive heart failure secondary to an infiltrative cardiomyopathic process (for example amyloid) or pericardial constriction;

8. Uncontrolled systemic hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >110) or systemic hypotension (systolic blood pressure < 90/60 mmHg);

9. Bariatric surgery or other surgeries that induce chronic malabsorption;

10. Anti-obesity drugs or diet regimen and unstable body weight three months prior to screening;

11. Treatment with systemic corticosteroids;

12. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells;

13. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control;

14. Participation in another trial with an investigational drug within 30 days of informed consent;

15. Alcohol or drug abuse within three months prior to informed consent that would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement;

16. Liver disease, defined by serum levels of alanine transaminase, aspartate transaminase, or alkaline phosphatase >3 x upper limit of normal as determined during screening;

17. Active malignancy at the time of screening;