None listed
Conditions
Brief summary
While SGLT2inhibitor drugs have been demonstrated to favourably affect outcomes in heart failure, the responsible mechanism(s) are completely unknown. We plan to conduct a single centre, phase 2/3, randomised, double blind, placebo-controlled clinical trial with two parallel arms, to investigate the mechanism of action of dapagliflozin (10mg daily), an SGLT2inhibitor, in non-diabetic or diabetic patients heart failure with reduced ejection fraction. By understanding the mode of action, we will then be able to administer these drugs in a personalized manner and to develop better therapies that specific address the key molecular or physiologic targets.
Interventions
Study medication of 10mg dapagliflozin (active) or 10mg of lactulose powder (control) tablets to be administered orally once daily in tablet formation at visit 2, following all inclusion and exclusion criteria having being met. At The next clinic visit (week 4 the patients will be asked to return study medication for tablet count and reconciliation to establish compliance. At the last clinic visit week 8 patients will be asked to return all unused study medication for further tablet reconcilia
Study medication of 10mg dapagliflozin (active) or 10mg of lactulose powder (control) tablets to be administered orally once daily in tablet formation at visit 2, following all inclusion and exclusion criteria having being met. At The next clinic visit (week 4 the patients will be asked to return study medication for tablet count and reconciliation to establish compliance. At the last clinic visit week 8 patients will be asked to return all unused study medication for further tablet reconciliation to establish compliance (>85%).
Sponsors
The Alfred Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
LVEF less than or equal to 40%. NYHA II-IV. Ischaemic or non-Ischaemic aetiology. Stable heart failure therapy for 1 month (a <50% adjustment to diuretics is permissible between day -14 and day -28). Patients may be non-diabetic or T2DM (on stable therapy >12 weeks defined as < ±20% variability in the average daily dose or oral agents and/or < ±10% daily variability in insulin dose).
Exclusion criteria
Unstable heart failure or haemodynamics (eg SBP<90mmHg, poorly controlled AF – rate>90/min). Recent or active unstable coronary disease in the past 2 months or PCI with the past month or CABG within 3 months. Type 1 diabetes. Poorly controlled BSL (fasting plasma glucose level > 13.3 mmol/L). History of ketoacidosis or hyperosmolar state/coma within 6 months. Ongoing therapy with an SGLT2 inhibitor or GLP-1 receptor agonist. On monoamine oxidase inhibitors or tricyclic antidepressants. Body mass index (BMI) <20.0 kg/m2 or >40 kg/m2. eGFR <30 ml/min/1.73 m2. Other life limiting lesion (expected survival <2 years) including malignancy, advanced respiratory, GI, neurologic, haematologic disease. Active substance abuse including EtOH. Inability to provide written informed consent.
Outcome results
None listed