Fluid Restriction in Heart Failure Versus Liberal Fluid Uptake

NCT04551729 | Completed DMC

• 1 other identifier: 75112
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 8

Brief Summary

Multi-centre open-label 1:1 randomized clinical trial in chronic heart failure patients on the effect of fluid restriction versus liberal fluid intake on quality of life.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)

  KCCQ Overall Summary Score (OSS) (scores minimum-maximum 0-100, higher scores indicate better outcome)

  3 months

Secondary Outcomes (6)

• Thirst distress

  3 months

• Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)

  3 months

• Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)

  3 months

• Quality of life assessed with EQ-5D-5L

  3 months

• Patient reported fluid intake

  6 weeks

Other Outcomes (11)

• Safety (death, all-cause or unplanned HF hospitalisation, the requirement of iv-loop diuretics)

  6 months

• Safety (death, all-cause or unplanned HF hospitalisation, the requirement of iv-loop diuretics)

  6 months

• Safety (acute kidney injury)

  6 months

Study Arms (2)

Fluid restriction

ACTIVE COMPARATOR

Patient will receive a lifestyle advice to adhere to fluid restriction of 1500cc/day for 3 months.

Behavioral: Lifestyle advice for liberal fluid intake

Liberal fluid intake

EXPERIMENTAL

Patient will receive a lifestyle advice for liberal fluid intake for 3 months.

Behavioral: Lifestyle advice for liberal fluid intake

Interventions

Lifestyle advice for liberal fluid intake BEHAVIORAL

Lifestyle advice for liberal fluid intake for 3 months

Fluid restriction; Liberal fluid intake

Eligibility Criteria

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

You may qualify if:

• Diagnosis of chronic HF with NYHA class II/III according to the prevailing guidelines \> 6 months prior to randomization (1)
• Adult (age ≥ 18 years)

You may not qualify if:

• Reversible cause of HF (thyroid disorders, severe anemia, vitamin deficiencies)
• Hospital admission for HF within 3 months of randomization
• Chronic HF with NYHA class IV
• Hyponatremia at baseline (sodium \<130mmol/l)
• Changes in HF medical therapy in last 14 days prior to randomization
• Estimated Glomerular Filtration Rate (eGFR) of \< 30ml/min/1.73 m2 at baseline
• Scheduled cardiac surgery within 3 months of randomization
• Recent (within 3 months) coronary intervention (PCI or CABG) or implantation of pacemaker device
• Comorbidity for which fluid restriction is advised by a different treating physician (e.g. nephrologist)
• Comorbidity with a life expectancy of less than 6 months
• The treating clinician believes that participation in the domain would not be in the best interests of the patient
• Inability to provide informed consent

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Maastricht University Medical Center: collaborator

Study Sites (8)

Radboud University Medical Center

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

Location

Hospital Group Twente

Almelo, Netherlands

Location

Rijnstate Hospital

Arnhem, Netherlands

Location

Zuyderland Ziekenhuis

Heerlen, Netherlands

Location

Dijklander Ziekenhuis

Hoorn, Netherlands

Location

Maastricht University Medical Centre

Maastricht, Netherlands

Location

Bernhoven Ziekenhuis

Uden, Netherlands

Location

Related Publications (2)

• Herrmann JJ, Beckers-Wesche F, Baltussen LEHJM, Verdijk MHI, Bellersen L, Brunner-la Rocca HP, Jaarsma T, Pisters R, Sanders-van Wijk S, Rodwell L, Van Royen N, Gommans DHF, Van Kimmenade RRJ. Fluid REStriction in Heart Failure vs Liberal Fluid UPtake: Rationale and Design of the Randomized FRESH-UP Study. J Card Fail. 2022 Oct;28(10):1522-1530. doi: 10.1016/j.cardfail.2022.05.015. Epub 2022 Jun 13.

  PMID: 35705150 BACKGROUND

• Herrmann JJ, Brunner-La Rocca HP, Baltussen LEHJM, Beckers-Wesche F, Bekkers SCAM, Bellersen L, van Eck JWM, Hassing HC, Jaarsma T, Linssen GCM, Pisters R, Sanders-van Wijk S, Verdijk MHI, Handoko ML, van der Meer P, Verbrugge FH, Januzzi JL Jr, Bayes-Genis A, Nieuwlaat R, Rodwell L, Gommans DHF, van Kimmenade RRJ. Liberal fluid intake versus fluid restriction in chronic heart failure: a randomized clinical trial. Nat Med. 2025 Jun;31(6):2062-2068. doi: 10.1038/s41591-025-03628-4. Epub 2025 Mar 30.

  PMID: 40159556 RESULT

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Roland van Kimmenade, MD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The members of the event adjudication committee will be blinded for treatment allocation. Moreover, the statistician who performs the primary analysis will be blinded for treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 16, 2020
• Study Start: April 21, 2021
• Primary Completion: September 23, 2024
• Study Completion: November 28, 2024
• Last Updated: April 18, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Weeks
• Access Criteria: These will be determined by the steering committee.

Locations

NL (8)