To determine whether dapagliflozin is superior to placebo, when added to standard of care, in reducing the composite of CV death and HF events (hospitalisation for HF or urgent HF visit) in patients with HF and preserved systolic function in* full…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to (first occurrence of):
1. CV death.
2. Hospitalisation for HF.
3. Urgent HF visit (e.g., emergency department or outpatient visit).
Secondary outcome
1. Total number of (first and recurrent) hospitalisations for HF and CV death.
2. Change from baseline in the total symptom score (TSS) of the KCCQ at 8
months.
3. Time to the occurrence of CV death
4. Time to the occurrence of death from any cause.
Background summary
The prevalence of chronic HF continues to increase globally. An estimated 38
million people are affected worldwide. Approximately half of all heart failure
patients have HFpEF. Risk of death for HFpEF patients is high, with annualised
mortality rate up to 15% in community settings.
However, patients with HFpEF have a particularly significant unmet medical need
given that outcome studies hitherto performed have not resulted in any approved
pharmacotherapy specifically for this condition. Recent data from
cardiovascular (CV) outcome trials of SGLT2 inhibitors (empagliflozin and
canagliflozin) indicate that treatment with SGLT2 inhibitors can reduce the
risk of CV death and hospitalisation due to HF in patients with T2D overall,
and in patients with T2D and concomitant HF.
Dapagliflozin is a potent, highly selective and orally active inhibitor of
human renal SGLT2. Dapagliflozin lowers HbA1c with a low risk of inducing
hypoglycaemia. In addition, dapagliflozin treatment has also been shown to
reduce weight and systolic blood pressure, and to have favourable effects on
increased blood uric acid, albuminuria, and arterial elasticity, conditions
which are associated with increased CV and renal risk. Dapagliflozin is
believed to be nephroprotective through non-glycaemic mechanisms. Dapagliflozin
has global marketing approval in approximately 90 countries with the most
recent estimate of cumulative post-marketing experience totalling over 1.6
million patient-years.
Study objective
To determine whether dapagliflozin is superior to placebo, when added to
standard of care, in reducing the composite of CV death and HF events
(hospitalisation for HF or urgent HF visit) in patients with HF and preserved
systolic function in
* full study population
* subpopulation with LVEF <60%
Study design
This is an international, multicentre, parallel-group, event-driven,
randomised, phase III, double-blind study in patients with HFpEF
Intervention
Patients will use either dapagliflozin 10 mg or placebo once daily.
Study burden and risks
The patients visit the hospital approximately 10 times over an average of 24
months (depending on when the subject is enrolled in the study). Study
participation will vary between approximately 15 - 33 months. The patients are
asked to keep in touch with the study doctor throughout the study.
During the study the following study procedures will be performed: physical
examination (±3 times), blood draw (±8 times), a pregnancy test is performed
(if applicable), (1 time), patients complete several questionnaires (±6 times)
and an ECG is taken (1 time). Blood sampling may cause some discomfort or can
cause a bruise. The use of study medication can cause side effects.
Prinses Beatrixlaan 582
Den Haag 2595 BM
NL
Prinses Beatrixlaan 582
Den Haag 2595 BM
NL
Listed location countries
Age
Inclusion criteria
1. Provision of signed informed consent prior to any study specific procedures.
2. Male or female patients age *40 years.
3. Documented diagnosis of symptomatic heart failure HFpEF
4. LVEF >40%, measured within the last 12 months prior to enrolment and
evidence of structural heart disease.
5. NT-pro BNP *300 pg/ml at Visit 1 for patients without ongoing atrial
fibrillation/flutter. If ongoing atrial fibrillation/flutter at Visit 1, NT-pro
BNP must be
*600 pg/mL.
6. Patients may be ambulatory, or hospitalized; patients must be off
intravenous heart
failure therapy (including diuretics)
Exclusion criteria
1. Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to
randomisation or
previous intolerance to an SGLT2 inhibitor
2. Type 1 diabetes mellitus (T1D)
3. eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at Visit 1
4. Systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements
5. Systolic BP*160 mmHg if not on treatment with *3 blood pressure lowering
medications
or *180 mmHg irrespective of treatments, on 2 consecutive measurements
6. MI, unstable angina, coronary revascularization within 12 weeks prior to
enrolment.
7. Planned coronary revascularization, ablation of atrial flutter/fibrillation
and valve
repair/replacement.
8. Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
9. Probable alternative or concomitant diagnoses which in the opinion of the
investigator
could account for the patient's HF symptoms and signs (e.g. anaemia,
hypothyroidism)
10. Body mass index >50 kg/m2
11. Previous cardiac transplantation, or complex congenital heart disease.
Planned cardiac
resynchronisation therapy.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201800080246-NL |
| CCMO | NL66182.100.18 |