Heart Failure, Heart Failure and Mildly Reduced Ejection Fraction, Heart Failure and Reduced Ejection Fraction
Conditions
Keywords
Guideline-Directed Medical Therapy, Limited Kidney Function Assessments
Brief summary
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) constitutes of four medications that substantially reduce morbidity and mortality, and improve quality of life. In routine clinical practice, various physician- and patient-related factors lead to suboptimal initiation and uptitration of GDMT to optimal dosing, which is associated with worse patient outcomes. A perceived major barrier to the optimalization of GDMT are changes in kidney function and electrolytes, which prompts physicians to halt uptitration, reduce doses, or even discontinue GDMT. Changes in kidney function and electrolytes during optimalization of GDMT are common, but not associated with adverse events. The hypothesis of this study is that a reduction in the number of kidney function assessments during initiation and uptitration of GDMT in HFrEF patients will lead to higher achieved doses of GDMT without safety concerns.
Detailed description
Objective: To assess the effect of a reduction in kidney function assessments during optimalization of GDMT in patients with HFrEF on the achieved GDMT doses, safety, and clinical outcomes. Study design: Randomized, controlled open-label study Study population: 344 patients with new-onset or sub-optimally treated HFrEF referred to the outpatient clinic for optimalization of GDMT Intervention (if applicable): Randomization to limited number of kidney function assessments or standard of care Primary endpoint: The achieved average percentage dose of reno-active GDMT at 6 months relative to optimal dose. Secondary endpoints: The achieved percentage dose of the individual reno-active GDMT drug classes at 6 months relative to optimal dose, and time to first occurrence of unplanned heart failure visit, heart failure hospitalization, or all-cause mortality till 9 months. Safety endpoints: Incidence of doubling of creatinine, estimated glomerular filtration rate (eGFR) \<20 mL/min/1.73 m2, potassium \>6 mmol/L, or potassium \<3.5 mmol/L at any timepoint. An additional composite kidney endpoint is defined as a combination of hospitalization for kidney failure, dialysis or end-stage kidney disease (eGFR \<15 mL/min/1.73 m2).
Interventions
OTHERBlinded kidney function assessments
Kidney function results will be blinded in the intervention group, except at baseline, three months, and six months.
Sponsors
Onze Lieve Vrouwe Gasthuis
Frisius Medisch Centrum
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able and willing to give written informed consent 2. Age ≥ 18 years 3. Diagnosed with HFrEF (LVEF≤ 45%) according to criteria from 2021 European Society of Cardiology guidelines for heart failure 4. Less than 100% target dose of 2 individual reno-active GDMT classes (ACEi/ARB/ARNI, MRA or SGLT-2i)
Exclusion criteria
1. eGFR\<25 mL/min/1.73 m2 measured up to 30 days before the first visit 2. Potassium \> 5.5 mmol/L or \<3.5 mmol/L at screening 3. Known intolerance or allergy to two individual GDMT 4. Signs of hemodynamic instability and/or cardiogenic shock 5. Decompensated heart failure requiring treatment with intravenous loop diuretics 6. Known concomitant structural kidney disease such as polycystic kidney disease or renal artery stenosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The achieved average percentage dose of reno-active GDMT at 6 months relative to optimal dose. | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| The achieved percentage dose of the individual reno-active GDMT drug classes at 6 months relative to optimal dose. | 6 months |
| The time to first occurrence of unplanned heart failure visit, heart failure hospitalization, or all-cause mortality till 9 months. | 9 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoint | Till 6 months | Incidence of doubling of creatinine, estimated glomerular filtration rate (eGFR) \<20 mL/min/1.73 m2, potassium \>6 mmol/L, or potassium \<3.5 mmol/L |
| The achieved average percentage dose of all GDMT at 6 months relative to optimal dose. | 6 months | — |
| Composite kidney endpoint | 6 months | Hospitalization for kidney failure, dialysis or end-stage kidney disease (eGFR \<15 mL/min/1.73 m2). |
| Percentage change in NT-pro BNP at 6 months | 6 months | — |
| Percentage change in loop diuretics at 6 months | 6 months | — |
Countries
Netherlands
Outcome results
None listed