Effects of Canagliflozin on Intravascular Volume and Hemodynamics

Phase 4

Withdrawn

• Conditions: Cardiovascular Diseases; Type2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Canagliflozin 300mg

• Registration Number: NCT03190798
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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.

Study Timeline

• Study First Submitted: 2017-06-15
• Study First Submitted QC: 2017-06-15
• Study First Posted: 2017-06-19
• Status Verified: 2017-07
• Study Start: 2017-09-01
• Last Update Submitted: 2017-10-10
• Last Update Posted: 2017-10-12
• Primary Completion: 2018-08-01
• Study Completion: 2018-08-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	Placebo	Assuming a 25% dropout rate, 11 individuals in the placebo group
Canagliflozin Group	Canagliflozin 300mg	Assuming a 25% dropout rate, 16 individuals in the canagliflozin group

Primary Outcome Measures

Name	Time	Method
Change in Pulmonary capillary wedge pressure (PCWP)	6 hours	The primary efficacy endpoint will be change in PCWP from baseline to end of acute administration monitoring period (6 hours).

Secondary Outcome Measures

Name	Time	Method
Change in Pulmonary capillary wedge pressure (PCWP)	4 weeks	The key secondary endpoint will be change in PCWP from baseline to 4 weeks.

Trial Locations

Locations (1)

The University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States