Treatment of Diabetes in Patients With Systolic Heart Failure

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02920918
• Collaborator: Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 36
• Location: 1
• Arms: 2
• Actual Duration (Months): 23
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Investigator Initiated Study to study the effects of Canagliflozin 100 milligrams (mg) vs Sitagliptin 100 mg on parameters of aerobic exercise capacity (peak oxygen consumption [VO2]) and ventilator efficiency (minute ventilation [VE]/carbon dioxide production [VCO2] slope) at cardiopulmonary exercise test (CPET) after 12 weeks of active treatment (primary endpoints). Blood pressure (BP), body water content, body composition, cardiac function, and diet will be also measured (secondary endpoints).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Systolic; Diabetes Mellitus, Type 2	Drug: Canagliflozin; Drug: Sitagliptin	Phase 4

Detailed Description

Investigator Initiated Study: Randomized, double-blinded, active-control clinical trial to determine the safety and efficacy of Canagliflozin and Sitagliptin in patients with type 2 diabetes and systolic heart failure (HF).

The investigators propose to study the effects of Canagliflozin 100 mg vs Sitagliptin 100 mg (both administered once daily for 12 weeks) on parameters of aerobic exercise capacity and ventilator efficiency by CPET after 12 weeks of active treatment. BP, body water content (Bioelectrical Impedance Analysis [BIA]), body composition (Dual-energy X-ray absorptiometry [DEXA]), cardiac function, diet and biomarkers will be also measured. Subjects with evidence of left ventricular hypertrophy will undergo cardiac magnetic resonance (CMR) imaging.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Active-Control Double-Blinded Study to Evaluate the Treatment of Diabetes in Patients With Systolic Heart Failure
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Sep 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Canagliflozin Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks.	Drug: Canagliflozin; Other Names: Invokana
Active Comparator: Sitagliptin Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks.	Drug: Sitagliptin; Other Names: Januvia

Outcome Measures

Primary Outcome Measures

1. Change From Baseline Aerobic Exercise Capacity at 12 Weeks [baseline and 12 weeks]

   Peak oxygen consumption (VO2) measured by maximal cardiopulmonary exercise test

2. Change From Baseline Ventilatory Efficiency at 12 Weeks [baseline and 12 weeks]

   Minute ventilation (VE) relative to CO2 production (VCO2) slope measured by cardiopulmonary exercise test

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Major Inclusion Criteria:

• Symptomatic stable heart failure (New York Heart Association (NYHA) functional classification II-III) with reduced left ventricular ejection fraction (LVEF) ≤40%

• Peak exercise limited by shortness of breath and associated with a respiratory exchange ratio (RER) >1.00 (reflecting maximal aerobic effort);

• Poorly controlled Type 2 Diabetes Mellitus (T2DM)(HbA1c levels between 7.0% and 10.0% if on a treatment regimen including insulin, or between 6.5% and 10.0% if not on an insulin regimen);

• Eighteen years of age or older.

Major Exclusion Criteria:

• Type I diabetes;

• Open label treatment with Sodium-GLucose coTransporter (SGLT)-2 inhibitors (within the past 3 months);

• Current treatment with thiazolidinedione (within the past 3 months);

• Chronic Renal Disease defined as Glomerular Filtration Rate (GFR) <50 ml•min-1/1.73m2 according to local laboratory

• Pregnancy or of child-bearing potential or lactating;

• Active or recent (within 2 weeks) genital/urinary infection;

• Concomitant conditions or treatment which would affect completion or interpretation of the study (i.e, physical inability to walk or run on a treadmill

• Inability to give informed consent.

Exclusion criteria specific to the cardiac magnetic resonance (CMR) substudy.

• Estimated GFR <60 ml•min-1/1.73m2

• Implantable cardioverter defibrillator, pacemaker or other implantable metal device not compatible with CMR scanning;

• Severe claustrophobia, inability to lay flat for up to 60 minutes, or other contraindication to CMR scanning.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• Janssen Scientific Affairs, LLC

Investigators

• Principal Investigator: Antonio Abbate, MD, PhD, Virginia Commonwealth University

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Dec 8, 2016

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT02920918
• Other Study ID Numbers: HM20007043; 28431754DIATBD
• First Posted: Sep 30, 2016
• Last Update Posted: Oct 29, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Virginia Commonwealth University: Systolic Heart Failure; Canagliflozin; Sitagliptin Phosphate; Type 2 Diabetes; SGLT2 inhibitor; DPPIV inhibitor
• Additional relevant MeSH terms: Heart Failure; Heart Failure, Systolic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Systolic Murmurs; Sitagliptin Phosphate; Canagliflozin

Study Results

Participant Flow

Arm/Group Title	Canagliflozin	Sitagliptin
Arm/Group Description	Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks. Canagliflozin	Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks. Sitagliptin
Period Title: Overall Study
STARTED	17	19
COMPLETED	17	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Canagliflozin	Sitagliptin	Total
Arm/Group Description	Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks. Canagliflozin	Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks. Sitagliptin	Total of all reporting groups
Overall Participants	17	19	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 88.2%	19 100%	34 94.4%
>=65 years	2 11.8%	0 0%	2 5.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (6.1)	54.3 (8.8)	56.0 (7.8)
Sex: Female, Male (Count of Participants)
Female	4 23.5%	4 21.1%	8 22.2%
Male	13 76.5%	15 78.9%	28 77.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 41.2%	12 63.2%	19 52.8%
White	10 58.8%	7 36.8%	17 47.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%	19 100%	36 100%
Peak Oxygen Consumption (mL/kg/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/kg/min]	16.2 (3.4)	15.3 (3.5)	15.7 (3.4)
Ventilator Efficiency (Unitless) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Unitless]	34.1 (6.1)	32.6 (7.2)	33.3 (6.7)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline Aerobic Exercise Capacity at 12 Weeks
Description	Peak oxygen consumption (VO2) measured by maximal cardiopulmonary exercise test
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Unadjusted p values were reported throughout, with statistical significance set at the 2-tailed 0.05 level. Only cases with available data used to compute the primary endpoint will be included in the analyses (16 subjects for canagliflozin group and 18 subjects for sitagliptin group).

Arm/Group Title	Canagliflozin	Sitagliptin
Arm/Group Description	Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks. Canagliflozin	Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks. Sitagliptin
Measure Participants	16	18
Mean (Standard Deviation) [mL/kg/min]	0.67 (2.10)	-0.53 (1.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin, Sitagliptin
	Comments	We expected a baseline peak oxygen consumption (VO2) of 14.5 mL/kg/min. A sample size of 40 patients per group (total of 80 patients) provided sufficient power to detect a mean difference in the interval change in peak VO2 of 1.50±1.76 mL/kg/min (primary endpoint) expected with Canagliflozin compared to Sitagliptin, which we predict to have no significant effect on peak VO2 (0±1.76 mL/kg/min).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Change From Baseline Ventilatory Efficiency at 12 Weeks
Description	Minute ventilation (VE) relative to CO2 production (VCO2) slope measured by cardiopulmonary exercise test
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Unadjusted p values were reported throughout, with statistical significance set at the 2-tailed 0.05 level. Only cases with available data used to compute the primary endpoint will be included in the analyses (16 subjects for canagliflozin group and 18 subjects for sitagliptin group).

Arm/Group Title	Canagliflozin	Sitagliptin
Arm/Group Description	Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks. Canagliflozin	Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks. Sitagliptin
Measure Participants	16	18
Mean (Standard Deviation) [Unitless]	-0.3 (4.1)	-0.3 (5.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin, Sitagliptin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	An Adverse Event (AE) is any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An event that is considered by the investigator(s) to be expected and related to the natural history of the disease is not considered an AE.
Arm/Group Title	Canagliflozin		Sitagliptin
Arm/Group Description	Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks. Canagliflozin		Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks. Sitagliptin
All Cause Mortality
	Canagliflozin		Sitagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/19 (0%)
Serious Adverse Events
	Canagliflozin		Sitagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/17 (17.6%)		1/19 (5.3%)
Cardiac disorders
Heart failure	1/17 (5.9%)	1	0/19 (0%)	0
Infections and infestations
Influenza B	0/17 (0%)	0	1/19 (5.3%)	1
Renal and urinary disorders
Dizziness and acute kidney injury	1/17 (5.9%)	1	0/19 (0%)	0
Vascular disorders
Occlusion superficial femoral artery	1/17 (5.9%)	1	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Canagliflozin		Sitagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/17 (41.2%)		6/19 (31.6%)
Cardiac disorders
Hypotensive event	2/17 (11.8%)	2	1/19 (5.3%)	1
Arrhythmic events	1/17 (5.9%)	1	1/19 (5.3%)	1
Infections and infestations
Genital infection	1/17 (5.9%)	1	1/19 (5.3%)	1
Renal and urinary disorders
Acute kidney injury	3/17 (17.6%)	3	3/19 (15.8%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.