DETERMINE-reduced – Dapagliflozin EffecT on ExeRcise capacity using a 6-MINutE walk test in patients with heart failure with reduced ejection fractio

Phase 1

• Conditions: Heart Failure Patients with Reduced Ejection Fraction (HFrEF); MedDRA version: 20.0Level: LLTClassification code 10078289Term: Heart failure with reduced ejection fractionSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-003442-16-SE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-11
• Last Update Posted: 11 May 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1.Provision of signed informed consent prior to any study specific procedures
2.Male or female, aged =18 years
3.Documented diagnosis of symptomatic HF (NYHA functional class II-IV), which has been present for at least 8 weeks, optimally treated with pharmacotherapy and/or device therapy with at least intermittent need for diuretic treatment.
4.LVEF=40% within the last 12 months prior to enrolment.
5.NT-proBNP =400 pg/mL (or if hospitalised for heart failure within the previous 12 months: NT-proBNP =300 pg/mL) at enrolment. If concomitant atrial fibrillation NT-proBNP must be =800 pg/mL (irrespective of history of heart failure hospitalisation)
6.Patients should receive background standard of care as described below:
All HFrEF patients should be treated according to locally recognised guidelines on standard of care treatment with both drugs and devices, as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated. Therapy should have been individually optimised and stable for =4 weeks (this does not apply to diuretics) before visit 1 and include (unless contraindicated or not tolerated):
•an ACE inhibitor, or ARB or sacubitril/valsartan
and
•a beta-blocker
and
•if considered appropriate by the patient's treating physician; a mineral corticoid receptor antagonist
7.6MWD=100 metres and =425 metres at both the Enrolment and Randomisation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1.Presence of any condition that precludes exercise testing.
2.Participation in a structured exercise training programme in the 1 month prior to screening or planned to start during the trial.
3.Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomisation or previous intolerance to an SGLT2 inhibitor.
4.Type 1 diabetes mellitus.
5.eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at visit 1, unstable or rapidly progressing renal disease at time of randomisation.
6.Systolic BP <95 mmHg on 2 consecutive measurements at 5-minute intervals, at Visit 1 or at Visit 2a/b.
7.Systolic BP =160 mmHg if not on treatment with =3 blood pressure lowering medications or =180 mmHg irrespective of treatments, on 2 consecutive measurements at 5-minute intervals, at Visit 1 (Enrolment) or at Visit 2a/b
8.Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment.
9.Myocardial infarction, unstable angina, coronary revascularization ablation of atrial flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronization therapy device within 12 weeks prior to enrolment.
10.Planned coronary revascularization, ablation of atrial flutter/fibrillation and/or valve
repair/replacement.
11.Stroke or transient ischemic attack within 12 weeks prior to enrolment.
12.Probable alternative or concomitant diagnoses which could account for the patient's HF symptoms and signs.
13.Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
14.Previous cardiac transplantation, or complex congenital heart disease. Planned cardiac resynchronisation therapy. Prior implantation of a ventricular assistance device or similar device, or implantation expected after randomization.
15.HF due to any of the following: known infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, or uncorrected primary valvular disease.
16.A life expectancy of <2 years due to any non-cardiovascular condition, based on Investigator's clinical judgement.
17.Active malignancy requiring treatment (with the exception of basal cell or squamous cell carcinomas of the skin).
18.Acute or chronic liver disease with severe impairment of liver function (eg, ascites, oesophageal varices, coagulopathy).
19.Women of child-bearing potential not willing to use a medically accepted method of contraception considered reliable in the judgment of the Investigator OR who have a positive urine pregnancy test at randomisation OR who are breast-feeding.
20.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study site).
21.Previous randomisation in the present study.
22.Participation in another clinical study with an IP or device during the last month prior to enrolment.
23.Inability of the patient, in the opinion of the Investigator, to understand and/or comply with study23Inability of the patient, in the opinion of the Investigator, to understand and/or comply with study medications, procedures and/or follow-up (especially completing ePRO assessments) OR any conditions that, in the opinion of the Investigator, may render the patient unable to complete the study. Therefore, patients who are unable to read (eg, are blind

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified