Heart FailurePhase 3SERENANCT04907123
Systematic Escalation of diuREtics With Natriuresis in Heart Failure Patients: SERENA Trial
A Phase 3 study testing Intensive sodiuria-guided diuretic treatment and Standard diuretic treatment in people with Heart Failure, run by University of Turin, Italy at 1 site in Italy.
Trial summary
The present is a multicenter, prospective, randomized, open-label, blinded end-point trial aiming to investigate the clinical benefit of a stepwise, natriuresis-driven diuretic strategy versus standard diuretic treatment in patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) and low… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Intensive sodiuria-guided diuretic treatment and Standard diuretic treatment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2021to Jan 2025
- Phase
- Phase 3
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admission for acute decompensate chronic heart failure or acute de novo heart failure
- Ejection Fraction <40%
- Severe signs and symptoms of congestion with modified wet score ≥ 12
- Spot urinary sodium excretion ≤ 70 mEq/L at 2 hours from first intravenous loop diuretic administration
- Systolic blood pressure ≥90 mmHg
Who cannot join
- Reversible etiology of acute heart failure (including acute coronary syndromes, myocarditis, acute pulmonary embolism, acute rhythm disorders, severe organic valve disease)
- Cardiogenic shock at admission or sign of hypoperfusion needing inotropic agents or mechanical circulatory support.
- eGFR lower than 15 ml/min/1.73m2 or dialysis
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
Italy1 site
A.O.U. Città della Salute e della Scienza di Torino
Torino, To, 10126
Simone Frea, MD, 0116335570, frea.simone@gmail.com
About this study
The present is a multicenter, prospective, randomized, open-label, blinded end-point trial aiming to investigate the clinical benefit of a stepwise, natriuresis-driven diuretic strategy versus standard diuretic treatment in patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) and low early urinary sodium excretion. The study will focus on patients at increased risk of resistance to diuretic therapy. In particular, patients admitted to the emergency department and cardiac intensive care unit due to an on-chronic or de-novo acute decompensated HF episode with a predominantly "wet" profile and low early spot urinary sodium (UNa+) excretion will be considered. Spot natriuresis is a low-cost, non-demanding laboratory test in use to identify diuretic-resistant patients with an inherent poor prognosis. Whether the early identification of diuretic resistant patients and the consequent more aggressive treatment may lead to a better outcome has not been demonstrated by randomized studies. This trial aims to assess if an intensive stepwise diuretic approach guided by systematic urinary output assessment including natriuresis evaluation versus a standard diuretic strategy based on urinary output alone effectively leads to faster euvolemia achievement and better prognosis in a real-world setting.
- Conditions
- Heart Failure
- Being tested
- Intensive sodiuria-guided diuretic treatment, Standard diuretic treatment
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive sodiuria-guided diuretic treatmentOther
Intensive stepwise diuretic treatment based on combined diuresis and urinary sodium assessment
Standard diuretic treatmentOther
Stepwise diuretic therapy based on diuresis assessment
| Study group | Role | What they receive |
|---|---|---|
| UNa+ Driven Intensive Therapy | Experimental | Ask patient to empty bladder. Start treatment (step 1). Re-evaluate patient every 6 hours; if therapeutic goal is not met, treat according to the following step.
Therapeutic goal: Spot Urinary Sodium > 70 mEq/L AND mean diuresis > 1,5 ml/kg/h Step 1 Furosemide i.v. continuous infusion (2 times oral daily dose; minimum dose: 240 mg die) Step 2 Double furosemide i.v. continuous infusion (maximal dose: 720 mg die) Step 3 Add oral metolazone 5 mg b.i.d. Step 4 Add oral acetazolamide 250 mg b.i.d. Receives: Other: Intensive sodiuria-guided diuretic treatment |
| Standard Therapy | Active comparator | Ask patient to empty bladder. Start treatment (step 1). Re-evaluate patient every 12 hours; if therapeutic goal is not met, treat according to the following step.
Therapeutic goal: mean diuresis > 1,5 ml/kg/h Step 1 Furosemide i.v. continuous infusion (2 times oral daily dose; minimum dose: 240 mg die) Step 2 Double furosemide i.v. continuous infusion (maximal dose: 720 mg die) Step 3 Add oral metolazone 5 mg b.i.d. Step 4 Add oral acetazolamide 250 mg b.i.d. Receives: Other: Standard diuretic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of significant reduction of congestion defined as absolute reduction of at least 1 point in wet score grading of congestion after 48 hours of treatment
Assessment of WET score (Gheorghiade et al, EJHF 2010)
Measured: 48 hours
Secondary outcomes (10)
Treatment failure, defined as persistent congestion (graded by wet score ≥12/20) after 24, 48 and 72 hours of diuretic treatment or need for renal replacement therapy.
Measured: 24,48 and 72 hours
Freedom from congestion at 48 hours, defined as jugular venous pressure of <8 cm, with no orthopnea and with trace peripheral edema or no edema
Measured: 48 hours
Worsening or persistent heart failure
worsening heart failure symptoms or failure of the patient's condition to improve with treatment requiring the initiation of intravenous inotropic therapy and/or the implementation of mechanical circulatory or ventilatory support up until 48 hours
Measured: 48 hours
Composite endpoint of all-cause mortality, urgent LVAD implant or Heart Transplantation at 30 and 90 days.
Measured: 30 and 90 days
All-cause mortality
Measured: 30 and 90 days
Cardiac cause mortality
including myocardial infarction, irreversible heart failure, cardiogenic shock, fatal arrhythmic events
Measured: 30 and 90 days
Rehospitalization for heart failure
Measured: 30 and 90 days
Worsening renal function
absolute increase in serum creatinine > 0.3 mg/dl or > 1,5-fold from baseline at any time from randomization to 48 hours
Measured: 48 hours
Incidence of severe hypokalemia, severe hyponatremia or symptomatic electrolytes disorders during treatment protocol
hypokalemia <3 mEq/L, severe hyponatremia <125 mEq/L
Measured: 72 hours
Severe symptomatic hypotension
Systolic arterial pressure < 80 mmHg
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study startOct 2021 (estimated)
- Primary completionOct 2024 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Simone Frea, A.O.U. Città della Salute e della Scienza - Molinette Hospital
- Investigators
- Simone Frea, MD, Principal investigator, A.O.U. Città della Salute e della Scienza, Torino, Italia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04907123
- Sponsor's protocol ID
- SERENA trial
- Acronym
- SERENA
- Status last verified
- May 2021
- First submitted
- 25 May 2021
- Last updated
- 28 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systematic Escalation of diuREtics With Natriuresis in Heart Failure Patients: SERENA Trial
- ClinicalTrials.gov ID
- NCT04907123
- Acronym / sponsor ID
- SERENA / SERENA trial
- Conditions
- Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 198 participants (estimated)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- Oct 2021 (estimated)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 28 May 2021 (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.
The present is a multicenter, prospective, randomized, open-label, blinded end-point trial aiming to investigate the clinical benefit of a stepwise, natriuresis-driven diuretic strategy versus standard diuretic treatment in patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) and low early urinary sodium excretion. The study will focus on patients at increased risk of resistance to diuretic therapy. In particular, patients admitted to the emergency department and cardiac intensive care unit due to an on-chronic or de-novo acute decompensated HF episode with a predominantly "wet" profile and low early spot urinary sodium (UNa+) excretion will be considered. Spot natriuresis is a low-cost, non-demanding laboratory test in use to identify diuretic-resistant patients with an inherent poor prognosis. Whether the early identification of diuretic resistant patients and the consequent more aggressive treatment may lead to a better outcome has not been demonstrated by randomized studies. This trial aims to assess if an intensive stepwise diuretic approach guided by systematic urinary output assessment including natriuresis evaluation versus a standard diuretic strategy based on urinary output alone effectively leads to faster euvolemia achievement and better prognosis in a real-world setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| UNa+ Driven Intensive Therapy | Experimental | Other: Intensive sodiuria-guided diuretic treatmentAsk patient to empty bladder. Start treatment (step 1). Re-evaluate patient every 6 hours; if therapeutic goal is not met, treat according to the following step. Therapeutic goal: Spot Urinary Sodium > 70 mEq/L AND mean diuresis > 1,5 ml/kg/h Step 1 Furosemide i.v. continuous infusion (2 times oral daily dose; minimum dose: 240 mg die) Step 2 Double furosemide i.v. continuous infusion (maximal dose: 720 mg die) Step 3 Add oral metolazone 5 mg b.i.d. Step 4 Add oral acetazolamide 250 mg b.i.d. |
| Standard Therapy | Active comparator | Other: Standard diuretic treatmentAsk patient to empty bladder. Start treatment (step 1). Re-evaluate patient every 12 hours; if therapeutic goal is not met, treat according to the following step. Therapeutic goal: mean diuresis > 1,5 ml/kg/h Step 1 Furosemide i.v. continuous infusion (2 times oral daily dose; minimum dose: 240 mg die) Step 2 Double furosemide i.v. continuous infusion (maximal dose: 720 mg die) Step 3 Add oral metolazone 5 mg b.i.d. Step 4 Add oral acetazolamide 250 mg b.i.d. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Admission for acute decompensate chronic heart failure or acute de novo heart failure
- Ejection Fraction <40%
- Severe signs and symptoms of congestion with modified wet score ≥ 12
- Spot urinary sodium excretion ≤ 70 mEq/L at 2 hours from first intravenous loop diuretic administration
- Systolic blood pressure ≥90 mmHg
Key exclusion criteria (4 listed)
- Reversible etiology of acute heart failure (including acute coronary syndromes, myocarditis, acute pulmonary embolism, acute rhythm disorders, severe organic valve disease)
- Cardiogenic shock at admission or sign of hypoperfusion needing inotropic agents or mechanical circulatory support.
- eGFR lower than 15 ml/min/1.73m2 or dialysis
- Pregnancy or breastfeeding
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 |
|---|---|---|
| Intensive sodiuria-guided diuretic treatmentIntensive stepwise diuretic treatment based on combined diuresis and urinary sodium assessment | Other | UNa+ Driven Intensive Therapy |
| Standard diuretic treatmentStepwise diuretic therapy based on diuresis assessment | Other | Standard Therapy |
Primary outcome
Evidence of significant reduction of congestion defined as absolute reduction of at least 1 point in wet score grading of congestion after 48 hours of treatment
Time frame: 48 hours
Assessment of WET score (Gheorghiade et al, EJHF 2010)
10 secondary outcomes
Treatment failure, defined as persistent congestion (graded by wet score ≥12/20) after 24, 48 and 72 hours of diuretic treatment or need for renal replacement therapy.
Time frame: 24,48 and 72 hours
Freedom from congestion at 48 hours, defined as jugular venous pressure of <8 cm, with no orthopnea and with trace peripheral edema or no edema
Time frame: 48 hours
Worsening or persistent heart failure
Time frame: 48 hours
Composite endpoint of all-cause mortality, urgent LVAD implant or Heart Transplantation at 30 and 90 days.
Time frame: 30 and 90 days
All-cause mortality
Time frame: 30 and 90 days
Cardiac cause mortality
Time frame: 30 and 90 days
Rehospitalization for heart failure
Time frame: 30 and 90 days
Worsening renal function
Time frame: 48 hours
Incidence of severe hypokalemia, severe hyponatremia or symptomatic electrolytes disorders during treatment protocol
Time frame: 72 hours
Severe symptomatic hypotension
Time frame: 72 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
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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.
Simone Frea, MD principal investigator
A.O.U. Città della Salute e della Scienza, Torino, Italia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intensive sodiuria-guided diuretic treatment and Standard diuretic treatment in people with Heart Failure, run by University of Turin, Italy at 1 site in Italy.
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 5 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Simone Frea, MD (+390116335570, frea.simone@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evidence of significant reduction of congestion defined as absolute reduction of at least 1 point in wet score grading of congestion after 48 hours of treatment (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 May 2021.