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

NCT07275437 | Not Yet Recruiting

• 1 other identifier: 22833
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Guideline-Directed Medical Therapy; Limited Kidney Function Assessments

Outcome Measures

Primary Outcomes (1)

• The achieved average percentage dose of reno-active GDMT at 6 months relative to optimal dose.

  6 months

Secondary Outcomes (2)

• 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 Outcomes (5)

• The achieved average percentage dose of all GDMT at 6 months relative to optimal dose.

  6 months

• Percentage change in NT-pro BNP at 6 months

  6 months

• Percentage change in loop diuretics at 6 months

  6 months

Study Arms (2)

Limited number of kidney function assessments

EXPERIMENTAL

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.

Other: Blinded kidney function assessments

Control

NO INTERVENTION

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

Interventions

Blinded kidney function assessments OTHER

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

Limited number of kidney function assessments

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to give written informed consent
• Age ≥ 18 years
• Diagnosed with HFrEF (LVEF≤ 45%) according to criteria from 2021 European Society of Cardiology guidelines for heart failure
• Less than 100% target dose of 2 individual reno-active GDMT classes (ACEi/ARB/ARNI, MRA or SGLT-2i)

You may not qualify if:

• eGFR\<25 mL/min/1.73 m2 measured up to 30 days before the first visit
• Potassium \> 5.5 mmol/L or \<3.5 mmol/L at screening
• Known intolerance or allergy to two individual GDMT
• Signs of hemodynamic instability and/or cardiogenic shock
• Decompensated heart failure requiring treatment with intravenous loop diuretics
• Known concomitant structural kidney disease such as polycystic kidney disease or renal artery stenosis

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Onze Lieve Vrouwe Gasthuis: collaborator
• Frisius Medisch Centrum: collaborator

Study Sites (2)

Onze Lieve Vrouwe Gasthuis

Amsterdam, North Holland, 1090 HM, Netherlands

Location

Frisius MC

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

MeSH Terms

Conditions

Heart Failure; Heart Failure, Systolic

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant prof. J.M. ter Maaten, MD, PhD

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: December 10, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: December 18, 2025

Record last verified: 2025-11

Locations

NL (2)