Effects of Canagliflozin on Intravascular Volume and Hemodynamics

The University of Texas System (UT)

Status and phase

Withdrawn

Phase 4

Conditions

Type2 Diabetes Mellitus

Cardiovascular Diseases

Treatments

Drug: Placebo

Drug: Canagliflozin 300mg

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03190798

HSC20170151H

DIA4028 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

This is a randomized, double-blind, placebo-controlled, parallel-group, single-center study (Figure 1). Thirty subjects will be randomized in a 3:2 randomization ratio to canagliflozin 300 mg once daily (QD) or placebo. The study will include a 3-week pretreatment screening phase and a 4-week double-blind treatment phase.

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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