Effects of Canagliflozin on Intravascular Volume and Hemodynamics

• Status: Withdrawn
• Trial end date: 2018-08-01
• Target enrollment: 0
• Participant gender: All

Summary

RESEARCH HYPOTHESIS

• In subjects with T2DM and HF, effect of canagliflozin will be superior to placebo for the change from baseline in PCWP after a single dose (6 hours post-dose) and after 4 weeks.

• Treatment with canagliflozin will be well tolerated over 4 weeks.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Devjit Tripathy; The University of Texas Health Science Center at San Antonio
• Collaborator: Janssen Scientific Affairs, LLC
• Treatments: Canagliflozin

Criteria

Inclusion Criteria:

• on stable doses (more than 3 months) of antihyperglycemic agents (except for an SGLT2 inhibitor and insulin)

• have an A1c ≥7% and ≤11%

• Estimated glomerular filtration rate (eGFR) must be ≥45 ml/min•1.73 m2

• have an NT-proBNP ≥500 pg/mL

• be on a stable dose of guideline-directed HF medication (i.e., angiotensin converting enzyme [ACE] inhibitor, angiotensin II receptor blocker [ARB], or angiotensin receptor neprilysin inhibitor [ARNI], β-blocker, diuretics, and/or mineralcorticoid receptor antagonist) for at least 4 weeks

• be on stable antihypertensive therapy for at least 2 months

Exclusion Criteria:

• T1DM

• repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose measurements ≥240 mg/dL or both

• during the pretreatment phase, NYHA Class IV HF status, uncontrolled hypertension as defined as systolic blood pressure (SBP) >160 or diastolic blood pressure (DBP) >100 mmHg

• liver disease (ALT or AST >3 x ULN)

• anemia Hb<10

• anticipated cardiac surgery or coronary intervention within the next 3 months

• severe unremediated valvular heart disease

• major CV event (e.g., MI, cerebrovascular accident) within 3 months prior to screening visit

• hospitalization for HF within 2 months prior to screening visit

• documented atrial fibrillation

• history of atraumatic amputation within past 12 months of screening or critical ischemia of the lower extremity within 6 months of screening

• an active skin ulcer, osteomyelitis, or gangrene

• have an allergy to iodocyanine green and inulin