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

A Randomized, Controlled Trial Investigating the Effectiveness and Safety of Uptitration of Guideline Directed MEdical Therapy in Heart Failure With a Reduced Ejection Fraction With Limited Standardized Kidney Function Assessments (RESUME-HF-Kidney)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Heart Failure and Reduced Ejection Fraction; Heart Failure and Mildly Reduced Ejection Fraction
• Intervention / Treatment: Other: Blinded kidney function assessments

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).

• Study Type: Interventional
• Enrollment (Estimated): 344
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1090 HM
      • Onze Lieve Vrouwe Gasthuis
      • Contact: Dr. P.E.J. van Pol, MD; Phone Number: +31 (0)20 599 91 11; Email: p.e.j.vanpol@olvg.nl
      • Principal Investigator: Petra E.J. van Pol, MD
  • Provincie Friesland
    • Leeuwarden, Provincie Friesland, Netherlands, 8934 AD
      • Frisius MC
      • Contact: Dr. C. da Fonseca MD; Phone Number: +31 (0)20 599 91 11; Email: carlos.da.fonseca@mcl.nl
      • Principal Investigator: Carlos da Fonseca, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Blinded kidney function assessments; Kidney function results will be blinded in the intervention group, except at baseline, three months, and six months.
No Intervention: Control; Participants will receive standard care, which includes frequent kidney function assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The achieved average percentage dose of reno-active GDMT at 6 months relative to optimal dose.	6 months

Secondary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Safety endpoint	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	Till 6 months
Composite kidney endpoint	Hospitalization for kidney failure, dialysis or end-stage kidney disease (eGFR <15 mL/min/1.73 m2).	6 months

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Onze Lieve Vrouwe Gasthuis; Frisius Medisch Centrum

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Estimated): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Guideline-Directed Medical Therapy; Limited Kidney Function Assessments
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Systolic
• Other Study ID Numbers: 22833

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No