None listed
Conditions
Brief summary
Type 2 Diabetes Mellitus (T2DM) is a major risk factor for heart failure (HF), with particularly poor prognosis and a 5 year survival rate of <25% in major studies. A central aim of DM management is optimal glycaemic control, however the impact of this on the development and progress of the heart failure syndrome is unknown. Prior to recent trials involving different SGLT-2 inhibitors, evidence that any glucose lowering therapy reduces the rates of cardiovascular events (in particular HF readmission) and death was not convincingly shown (ACCORD, ADVANCE, UKPDS, VADT) The exact mechanisms of the benefits seen with the SGLT-2 Inhibitors, although postulated, are unclear. It is proposed that SGLT-2 inhibitors could demonstrate short term improvements in functional capacity, congestion parameters, biochemical, electrocardiographic and ,echocardiographic structural and functional parameters in participants with clinical HF and T2DM.
Interventions
Twenty five patients with existing T2DM who are admitted to hospital with acute decompensated heart will be given either placebo or the oral SGLT-2 inhibitor dapagliflozin at 10mg daily dose in this crossover trial with a two week window from hospital discharge and a two week washout period between crossover.
The participants will return to the clinic for regularly scheduled visits. They will have a randomisation visit 2 weeks after hospital discharge, and visits at 4, 6 and 8 weeks after rand
Twenty five patients with existing T2DM who are admitted to hospital with acute decompensated heart will be given either placebo or the oral SGLT-2 inhibitor dapagliflozin at 10mg daily dose in this crossover trial with a two week window from hospital discharge and a two week washout period between crossover. The participants will return to the clinic for regularly scheduled visits. They will have a randomisation visit 2 weeks after hospital discharge, and visits at 4, 6 and 8 weeks after randomisation. Their medication compliance will be assessed by study staff at 2 weekly intervals when they return. Duration of treatment is that active study medication will only be given for 2 out of 8 weeks. Participant follow up –The participants will be followed up in clinic at their scheduled visits and the following information will be collected: Demographic profile: age, sex, marital status, social support, education, ethnicity and first language -Medical history -Treatment(s): existing prescribed medications and type of non-pharmacologic treatments (if any). -HF therapy (ACE inhibitors/ARB, beta-blockers, mineralocorticoid antagonists, ivabradine, angiotensin receptor neprilysin inhibitor) Permanent pacemaker/ Implantable Cardiac Defibrillator/ Cardiac Resynchronisation Therapy --Medication review - Clinical profile: this includes a physical assessment, height, weight, waist and hip circumference, vital signs (heart rate, blood pressure, and respiratory rate) -NYHA class. -6MWT and doorbell test -Kansas City Cardiomyopathy Questionnaires (KCCQ) -Echocardiogram and lung ultrasound at the time of echocardiogram -Basic blood tests -ECG, Holter monitor -24 hour blood pressure wrist monitor -Arterial tonometry and radial artery applanation tonography (SphygmoCor)
Sponsors
Flinders Medical Centre
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
•Patients with previously diagnosed T2DM for which they are on prescribed glucose lowering therapy. •Admission with an episode of decompensated heart failure. •Heart failure with reduced ejection fraction (HFrEF) (documented EF <=40%) •Qualify for add on SGLT2 inhibitor glucose lowering therapy for DM according to current guidelines •Patients who are being prescribed an add-on SGLT2 inhibitor (long term) by the responsible hospital medical team on the basis of their medical judgment (independent of the trial) for the approved PBS indication of suboptimal glycaemic control. •On guideline-recommended therapy for their heart failure (or documented reason why not) •Clinically stable at the time of recruitment •Live within a geographically accessible area for follow-up
Exclusion criteria
•Age less than 18 years •Unable to provide written informed consent to participate in the study (this includes the inability to communicate fluently with the investigator and cognitive incompetence) •Valvular stenosis of > moderate severity •Valvular regurgitation >=severe and planning corrective invasive therapy •Oncologic (or other) life expectancy <12 months or any other medical condition (including pregnancy) that results in the belief (deemed by the Chief Investigators) that it is not medically appropriate for the patient to participate in this trial •eGFR <60 ml/min/1.73m2 •Past history of ketoacidosis •Past history of frequent or significant genital candidiasis •Already taking or past intolerance to an SGLT2 inhibitor •Pregnant, breastfeeding or women of child bearing potential without adequate contraception •Elective surgery in the next 8 weeks
Outcome results
None listed