Effectiveness and Safety of Uptitration of Guideline Directed MEdical Therapy in Heart Failure With Reduced Ejection Fraction With Limited Kidney Function Assessments

NCT ID: NCT07275437

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 344 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-01
• Study Completion Date: 2030-01-01

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).

Conditions

Heart Failure; Heart Failure and Reduced Ejection Fraction; Heart Failure and Mildly Reduced Ejection Fraction

Keywords

Guideline-Directed Medical Therapy; Limited Kidney Function Assessments

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Limited number of kidney function assessments

Participants in this arm will have standardized kidney function assessments at baseline, three months, and six months. Kidney function assessments in between these moments will be blinded in the electronic patient dossier. Unblinding will be performed if the results are significantly abnormal.

Group Type: EXPERIMENTAL

Blinded kidney function assessments

Intervention Type: OTHER

Kidney function results will be blinded in the intervention group, except at baseline, three months, and six months.

Control

Participants will receive standard care, which includes frequent kidney function assessments.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Blinded kidney function assessments

Kidney function results will be blinded in the intervention group, except at baseline, three months, and six months.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Onze Lieve Vrouwe Gasthuis

OTHER

Sponsor Role: collaborator

Frisius Medisch Centrum

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Jozine ter Maaten

Assistant prof. J.M. ter Maaten, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Onze Lieve Vrouwe Gasthuis

Amsterdam, North Holland, Netherlands

Frisius MC

Leeuwarden, Provincie Friesland, Netherlands

Countries

Netherlands

Facility Contacts

Dr. P.E.J. van Pol, MD

Role: primary

Dr. C. da Fonseca MD

Role: primary

Other Identifiers

22833

Identifier Type: -

Identifier Source: org_study_id