Clinical trial NCT03190798: Effects of Canagliflozin on Intravascular Volume and Hemodynamics
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study to Evaluate the Effects of Canagliflozin on Intravascular Volume and Hemodynamics in Subjects With Type 2 Diabetes Mellitus and Heart Failure
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Type2 Diabetes Mellitus
Cardiovascular Diseases
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2017-06-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Change in Pulmonary capillary wedge pressure (PCWP)
timeFrame: 6 hours
Secondary outcomes:
measure: Change in Pulmonary capillary wedge pressure (PCWP)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Devjit Tripathy, MD
role: PRINCIPAL_INVESTIGATOR
References: