Heart FailureFRESH-UPNCT04551729
Fluid Restriction in Heart Failure Versus Liberal Fluid Uptake
A study testing Lifestyle advice for liberal fluid intake in people with Heart Failure, run by Radboud University Medical Center at 8 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Lifestyle advice for liberal fluid intake
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 504 participants
- Where
- 8 sitesNetherlands
- Study dates
- 21 Apr 2021to 28 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of chronic HF with NYHA class II/III according to the prevailing guidelines > 6 months prior to randomization (1)
- Adult (age ≥ 18 years)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Netherlands8 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
Hospital Group Twente
Almelo
Rijnstate Hospital
Arnhem
Zuyderland Ziekenhuis
Heerlen
Dijklander Ziekenhuis
Hoorn
Maastricht University Medical Centre
Maastricht
Radboud University Medical Center
Nijmegen, Gelderland, 6525GA
Bernhoven Ziekenhuis
Uden
About this study
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
- Being tested
- Lifestyle advice for liberal fluid intake
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifestyle advice for liberal fluid intakeBehavioural
Lifestyle advice for liberal fluid intake for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Fluid restriction | Active comparator | Patient will receive a lifestyle advice to adhere to fluid restriction of 1500cc/day for 3 months. Receives: Behavioral: Lifestyle advice for liberal fluid intake |
| Liberal fluid intake | Experimental | Patient will receive a lifestyle advice for liberal fluid intake for 3 months. Receives: Behavioral: Lifestyle advice for liberal fluid intake |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 3 months
Secondary outcomes (6)
Thirst distress
Thirst Distress Scale for patients with Heart Failure (scores minimum-maximum 8-40, higher scores indicate worse outcome)
Measured: 3 months
Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)
KCCQ Clinical Summary Score (CSS) and each of the KCCQ domains (scores minimum-maximum 0-100, higher scores indicate better outcome)
Measured: 3 months
Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Proportion of patients with clinically meaningful changes in KCCQ-OSS and KCCQ-CSS (improved: ≥5 points increase; stable: <5 points increase or decrease; declined: ≥5 points decrease)
Measured: 3 months
Quality of life assessed with EQ-5D-5L
EQ-5D-5L (First part; scores minimum-maximum 0-1. Second part; (scores minimum-maximum 0-100, higher scores indicate better outcome)
Measured: 3 months
Patient reported fluid intake
Patient reported fluid intake for 1 week in a fluid intake diary
Measured: 6 weeks
Safety (Death, all-cause hospitalisations, iv loop diuretic treatment)
Composite of death, hospitalisations and iv loop diuretic treatment
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start21 Apr 2021
- Primary completion23 Sep 2024
- Study completion28 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 504 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center
- Responsible party
- Sponsor
- Investigators
- Roland van Kimmenade, MD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04551729
- Sponsor's protocol ID
- 75112
- Acronym
- FRESH-UP
- Status last verified
- Dec 2024
- First submitted
- 10 Sep 2020
- Last updated
- 18 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Other investigators can submit a proposal to the steering committee for the sharing of data. This proposal will be discussed in the steering committee.
Publications
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.
PubMed 35705150Herrmann 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.
PubMed 40159556
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluid Restriction in Heart Failure Versus Liberal Fluid Uptake
- ClinicalTrials.gov ID
- NCT04551729
- Acronym / sponsor ID
- FRESH-UP / 75112
- Conditions
- Heart Failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 504 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center
- Study start
- 21 Apr 2021 (actual)
- Primary completion
- 23 Sep 2024 (actual)
- Study completion
- 28 Nov 2024 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluid restriction | Active comparator | Behavioral: Lifestyle advice for liberal fluid intakePatient will receive a lifestyle advice to adhere to fluid restriction of 1500cc/day for 3 months. |
| Liberal fluid intake | Experimental | Behavioral: Lifestyle advice for liberal fluid intakePatient will receive a lifestyle advice for liberal fluid intake for 3 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of chronic HF with NYHA class II/III according to the prevailing guidelines > 6 months prior to randomization (1)
- Adult (age ≥ 18 years)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lifestyle advice for liberal fluid intakeLifestyle advice for liberal fluid intake for 3 months | Behavioural | Fluid restriction, Liberal fluid intake |
Primary outcome
Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: 3 months
KCCQ Overall Summary Score (OSS) (scores minimum-maximum 0-100, higher scores indicate better outcome)
6 secondary outcomes
Thirst distress
Time frame: 3 months
Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: 3 months
Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: 3 months
Quality of life assessed with EQ-5D-5L
Time frame: 3 months
Patient reported fluid intake
Time frame: 6 weeks
Safety (Death, all-cause hospitalisations, iv loop diuretic treatment)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Background: PubMed 35705150Herrmann 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.
- Results publication: PubMed 40159556Herrmann 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.
- Individual participant dataSharing planned: Yes. Other investigators can submit a proposal to the steering committee for the sharing of data. This proposal will be discussed in the steering committee.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roland van Kimmenade, MD PhD principal investigator
Radboud University Medical Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lifestyle advice for liberal fluid intake in people with Heart Failure, run by Radboud University Medical Center at 8 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quality of life assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04551729, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2025.