Status:
COMPLETED
Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects
Lead Sponsor:
NHS Greater Glasgow and Clyde
Collaborating Sponsors:
University of Glasgow
Conditions:
Heart Failure
Diabetes Mellitus
Eligibility:
All Genders
18+ years
Phase:
PHASE4
Brief Summary
The investigators hypothesise that empagliflozin 10mg daily will have haemodynamic, cardiac, and renal benefits compared to placebo over 36 weeks in heart failure patients with type 2 diabetes (or pre...
Detailed Description
The results of the EMPA-REG OUTCOME trial on CVD outcomes and heart failure hospitalisation suggests that empagliflozin works quickly to lessen CVD mortality and reduce heart failure hospitalisations ...
Eligibility Criteria
Inclusion
- Written informed consent
- Male or female, aged ≥18 years age
- Type 2 DM (diet-controlled or on stable treatment) or prediabetes
- Stable treatment defined as no change in oral therapy agents or doses for diabetes mellitus and (where applicable) \<10% change in average total daily insulin dose over last 6 weeks
- HbA1c ≤97 mmol/mol (11%) (routine available data from medical records, recorded in the last year)
- Prediabetes defined as HbA1c 39-47 mmol/mol (5.7-6.4%) at the time of screening (specifically for the prediabetes group, HbA1c will be repeated at the time of screening if there are no recent results within the last 3 months, in order to confirm the diagnosis of prediabetes)
- Heart failure (as defined by the presence of typical signs and symptoms of heart failure with documented reduced ejection fraction (ref SIGN and ESC guidelines))
- NYHA class II-IV
- LVEF ≤40%
- On stable doses of ACEI, ARB or ARNI for 4 weeks prior to randomisation unless contraindicated or not tolerated. They should also be taking a beta-blocker at a stable dose for 4 weeks unless contraindicated or not tolerated
- Women of childbearing potential (WOCBP) must be currently adhering to, or be willing to use, highly effective birth control methods for study treatment duration including:
- Combined hormonal contraception (oestrogen and progestogen containing medication) either orally, intravaginally, or transdermally
- Progesterone only hormonal contraception either orally, injected, or implanted
- Intrauterine device (IUD)
- Intrauterine hormone release system (IUS)
- Bilateral fallopian tube occlusion
- Vasectomised partner
- Complete sexual abstinence where this is their preferred and usual lifestyle
- WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilisation (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal. Post-menopausal is defined as:
- o Women who have had amenorrhea for ≥12 consecutive months (without another medical cause)
Exclusion
- Type 1 DM
- History of hospital admission with a diagnosis of diabetic ketoacidosis (DKA)
- Insulin use within 1 year of diagnosis of diabetes
- History of acute or chronic pancreatitis
- eGFR \<30 ml/min/1.73m2 (derived using CKD EPI)
- Persistent/permanent atrial fibrillation/flutter (conditions which significantly impede MRI image interpretability)
- Acute coronary syndrome, stroke or surgery within 1 month (small type 2 MI in the context of acute HF does not apply)
- BMI \>52 kg/m2
- Liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal (ULN) during screening
- Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
- Any condition outside the cardiovascular and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator's clinical judgement
- Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma, adjuvant hormonal therapy for breast cancer and hormone therapy for prostate cancer)
- Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia)
- Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
- Any uncontrolled endocrine disorder except Type 2 DM
- Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake
- Known hypersensitivity to the empagliflozin or excipients
- Known hypersensitivity to gadolinium
- Inability to give informed consent
- SGLT2 inhibitor use (current or previous)
- Devices or any other contraindication to MRI scans
- Currently pregnant, planning pregnancy, or currently breastfeeding
- History of previous lower limb amputation
- Current participation in another interventional medical study or within the last 90 days
- Anyone who, in the investigators' opinion, is not suitable to participate in the trial for other reasons
Key Trial Info
Start Date :
March 16 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 28 2020
Estimated Enrollment :
105 Patients enrolled
Trial Details
Trial ID
NCT03485092
Start Date
March 16 2018
End Date
March 28 2020
Last Update
September 18 2020
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Queen Elizabeth University Hospital
Glasgow, Scotland, United Kingdom, G51 4TF