Value of SGLT2 Inhibitor (Dapagliflozin) as an Added Therapy in Diabetic Patients With Heart Failure With Reduced Ejection Fraction; Randomized Controlled Clinical Trial

NCT04304560 | Unknown Phase 2 DMC

• 1 other identifier: DDHFrEF
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). Whereas the prevalence of HF in the general population is 1-4%, it reaches approximately 12% in T2DM patients. In 1972, Rubler reported a specific diabetes-associated cardiac injury called diabetic cardiomyopathy. This cardiomyopathy is defined by ventricular dysfunction occurring without coronary disease or hypertension. Diabetic cardiomyopathy is also characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. A large body of work indicates that diabetic cardiomyopathy is associated with altered cardiac energy metabolism. Indeed, in obese T2DM patients, heart lipid uptake is increased. Several studies support that free fatty acid (FFA) accumulation leads to the increased production of diacylglycerol (DAG), ceramides and reactive oxygen species (ROS), affecting cardiac insulin sensitivity and cardiac contractility. On the other hand, hyperglycemia and glucose overload have been involved in cardiac hypertrophy and dysfunction in the context of T2DM and obesity. The diabetic heart is simultaneously characterized by impaired insulin-stimulated glucose uptake and obvious signs of glucose overload, such as ROS and advanced glycation end-product (AGE) production as well as hexosamine pathway chronic activation. Interestingly, when comparing diabetic and nondiabetic obese patients, we previously demonstrated that hyperglycemia per se plays a central role in the impaired cardiac mitochondrial activity associated with myocardial contractile dysfunction.

Conditions

Heart Failure With Reduced Ejection Fraction (HFrEF); Diabete Type 2; Cardiomyopathies

Outcome Measures

Primary Outcomes (3)

• LV dimensions

  Echocardiography

  3 Months

• Systolic function

  Echocardiography

  3 Months

• Diastolic Function

  Echocardiography

  3 Months

Secondary Outcomes (4)

• HbA1c

  3 Months

• Myeloperoxidase (MPO)

  3 Months

• N-terminal pro b-type Natriuretic Peptide (proBNP-N)

  3 Months

• Galectin -3

  3 Months

Study Arms (2)

Control Group

PLACEBO COMPARATOR

Control group will receive the standard therapy for DM \& HFrEF and placebo.

Drug: Placebo oral tablet

Dapagliflozin

EXPERIMENTAL

Intervention group will receive 10mg of Dapagliflozin (Forxiga) ® tablet and standard therapy for HFrEF.

Drug: Dapagliflozin 10 MG

Interventions

Dapagliflozin 10 MG DRUG

inhibitor of sodium-glucose cotransporter 2

Also known as: Forxiga

Dapagliflozin

Placebo oral tablet DRUG

Similar Placebo oral tablet

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with type-2 diabetes history \>=5 years
• HbA1C 6-10% with glucose control medications including insulin, metformin or sulfonylurea
• Medically stable
• Willing to participate and sign informed consent.

You may not qualify if:

• GFR \<60 mL/min/1.73 m2
• Unstable or rapidly progressive renal disease
• Hypotension with SBP \<100 mmHg
• Hypersensitivity to dapagliflozin or any excipients
• Patients with severe hepatic impairment (Child-Pugh class C)
• Patients with active hepatitis B or C infection
• Any of the following CV/Vascular Diseases within 3 months prior to signing the consent at enrollment, as assessed by the investigator:
• Myocardial infarction
• Cardiac surgery or revascularization (CABG/PTCA)
• Unstable angina
• HF New York Heart Association (NYHA) Class IV
• Transient ischemic attack (TIA) or significant cerebrovascular disease
• Unstable or previously undiagnosed arrhythmia
• Established PAD

Sponsors & Collaborators

• Damanhour University: lead
• Menoufia University: collaborator

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiomyopathies

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: RCT

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 11, 2020
• Study Start: March 1, 2020
• Primary Completion: March 1, 2021
• Study Completion: April 1, 2021
• Last Updated: March 11, 2020

Record last verified: 2020-03