None listed
Conditions
Brief summary
The ivaBRADine to reduce mICrovasculAR complications of type 2 DIAbetes mellitus (BRADICARDIA) study is a prospective randomised open blinded end-point (PROBE) design trial funded by a Heart Foundation Vanguard Grant. It will test the hypothesis that heart rate reduction improves (or reduces progression of) microvascular complications in type 2 diabetes mellitus. It will randomise 50 patients with type 2 diabetes mellitus 1:1 to ivabradine (in the intervention group) or no treatment/standard care (in the control group). Ivabradine works selectively on the sino-atrial node to slow heart rate without any other significant haemodynamic effects. The primary outcome will be change in urinary albumin creatinine ratio (UACR, the average of three first-void urine samples). The secondary outcomes will be change in retinal microvascular structure/pattern from retinal imaging and skin micro-vessel function using the laser Doppler and 3-D optical coherence tomography (OCT) techniques. These outcomes will be measured at baseline and at 90 days post intervention commencement.
Interventions
The ivaBRADine to reduce mICrovasculAR complications of type 2 DIAbetes mellitus (BRADiCARDIA) study is a prospective randomised open blinded end-point (PROBE) design trial. This study examines the hypothesis that heart rate reduction improves, or reduces the progression of, microvascular (dys)function in patients with type 2 diabetes mellitus. The study will randomise 50 patients with type 2 diabetes mellitus 1:1 (25 given ivabradine 5 mg twice daily increasing to 7.5 mg twice daily in addition
The ivaBRADine to reduce mICrovasculAR complications of type 2 DIAbetes mellitus (BRADiCARDIA) study is a prospective randomised open blinded end-point (PROBE) design trial. This study examines the hypothesis that heart rate reduction improves, or reduces the progression of, microvascular (dys)function in patients with type 2 diabetes mellitus. The study will randomise 50 patients with type 2 diabetes mellitus 1:1 (25 given ivabradine 5 mg twice daily increasing to 7.5 mg twice daily in addition to standard care in the intervention group vs 25 given standard care in the control group) for 90 days. Study personnel who conducts assessments will be unaware of treatment allocation (blinded assessment). Clinical data, medications, estimated glomerular filtration rate (GFR), urinary albumin creatinine ratio (UACR), retinal imaging and skin micro-vessel function tests (laser Doppler assessment and 3-D forearm skin optical coherence tomography (OCT) examinations at rest and during maximal hyperaemia) will be undertaken and recorded at baseline (pre-intervention). UACR will be the average of three first void urine samples taken on three separate days in the week prior to commencing treatment and separate from the ‘screening’ measures which would have been conducted to determine eligibility. After baseline assessments, study participants in the intervention group will commence on ivabradine 5 mg twice daily (t=0). Patients will be reviewed at 30 (±3) days (t=30), and if the participant is tolerating their medication and their heart rate is above 60 bpm, treatment will be increased to ivabradine 7.5 mg twice daily. After 90 (±3) days (t=90), patients will attend for their final visit. Patients will be requested to bring three first morning void urine samples collected on three separate days in the prior week for their 90-day UACR. Patients will also undergo further retinal imaging, laser Doppler assessment and skin OCT examination. Clinical data, medications and GFR will be re-assessed. Information will be collected on the tolerability of the study medication and reported compliance. A pill count of remaining study medication will also be recorded.
Sponsors
Royal Perth Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used) (Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with type 2 diabetes mellitus (T2DM), plus all of the following: • albuminuria (UACR > 2.5 mg/mmol in men, > 3.5 mg/mmol in women), documented on at least two out of three first void morning urine samples; and • resting heart rate (HR) of > 70 bpm on two consecutive electrocardiograms (ECGs) at least 24 hours apart and with the second of these < 24 hours before randomisation; and • in sinus rhythm with no history of atrial fibrillation; and • stable treatment of T2DM and hypertension for a minimum of three months (HbA1c < 8.5% and BP less than or equal to 140/90); and • optimal and stable treatment of coronary heart disease and/or heart failure for a minimum of three months (to minimise risk of titration of other medications that might impact on UACR and HR).
Exclusion criteria
Patients with: • current treatment with or previous intolerance of ivabradine; or • current treatment with diltiazem or verapamil (contraindicated by manufacturer); or • transplanted heart, implanted pacemaker, cardioverter-defibrillator or cardiac resynchronization therapy; or • scheduled for coronary revascularization, or likely to require surgery for valvular disease; or • sick sinus syndrome, sinoatrial block, congenital long QT, 2nd degree and complete atrio-ventricular block; or • abnormal serum creatinine (> 200 mol/L), transaminases (> 3 x ULN), or haemoglobin (men < 110 g/L, women < 100 g/L); or • pregnant, lactating or women of childbearing age not using contraception.
Outcome results
None listed