Heart FailurePhase 4IMPROVE-HFNCT02643147
Loop Diuretic Dosage in Patients With Acute Heart Failure and Renal Failure: Conventional Versus Carbohydrate Antigen 125-guided Therapy (IMPROVE-HF)
A Phase 4 study testing CA125 guided strategy and Conventional Strategy in people with Heart Failure, run by Fundación para la Investigación del Hospital Clínico de Valencia at 1 site in Spain.
Trial summary
Worsening renal function (WRF) is a frequent finding in patients with decompensated acute heart failure (AHF) and it is associated to increased length of hospitalization and higher morbidity and mortality. 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?
- CA125 guided strategy and Conventional Strategy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2015to 30 Jan 2017
- Phase
- Phase 4
- 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
- Patients with the diagnosis of acute heart failure (AHF) and the concurrence of the following conditions:
- Presence of symptoms (dyspnea at rest or minimal exertion) and signs attributable to congestion (signs of congestion on chest radiography, or presence of peripheral edema or ascites, or jugular venous distension at 45 degrees or presence of crackles on auscultation).
- Elevated natriuretic peptide (NT-proBNP> 1000 pg/ml or BNP> 100 mg/dl).
- Creatinine ≥1,4 mg/dl on admission, provided that the estimated glomerular filtration rate less than 60 ml / min / m2.
- Intent to be treated with loop diuretics intravenously.
Who cannot join
- Life expectancy less than 6 months of life due to other comorbid conditions.
- Cardiogenic shock.
- Diagnosis of acute coronary syndrome in the previous 30 days.
- Pregnancy at the time of inclusion.
- Restrictive or Obstructive pulmonary disease or severe degree.
- Chronic renal insufficiency in stage V (estimated glomerular filtration rate <15 ml / min / m2) or patient previously included in known dialysis program.
- Participation in another clinical trial randomized at the time of inclusion.
- Temperature ≥38 ° C or diagnosis of pneumonia.
Trial locations and contacts
1 site in 1 country.
About this study
Worsening renal function (WRF) is a frequent finding in patients with decompensated acute heart failure (AHF) and it is associated to increased length of hospitalization and higher morbidity and mortality. Traditionally, WRF in AHF setting has been attributed to low cardiac output, but recent evidence also suggests venous congestion play a crucial role. Loop diuretics are the mainstay treatment of AHF, but their use traditionally has been associated to WRF, but also renal function improvement in patients with unequivocal signs of congestion. Nevertheless, traditional symptoms or signs of patients with AHF have shown a limited accuracy to neither identify nor quantify the degree of venous congestion. Recent authors have reported that plasma levels of antigen carbohydrate 125 (CA125) are closely related to the degree of venous congestion.
The investigators hypothesize that CA125 may have a role for identifying the hyperhydrated (High CA125) patients that need high loop diuretic doses, and those with normal CA125 values needing low loop diuretic doses. In this randomized study (1:1) the investigators seek to evaluate whether a CA125 loop diuretic guided management therapy is superior to a standard strategy. The primary endpoint is the magnitude of changes of renal function at 24 and 72 hours after initiation of intravenous diuretic in an acute worsening of heart failure
- Conditions
- Heart Failure
- Being tested
- CA125 guided strategy, Conventional Strategy
- Keywords
- Heart Failure, Renal Failure, Biomarker guided-therapy, Loop diuretics, Carbohydrate antigen 125
- Medical subject headings
- Heart Failure, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CA125 guided strategyDrug
Also called Loop diuretic (Furosemide) dosage in CA125 ≤35 U/ml patients
Initial dose of intravenous furosemide ≤80 mg / day regardless of prior dose of loop diuretics who were receiving.
CA125 guided strategyDrug
Also called Loop diuretic dosage (Furosemide) in CA125 >35 U/ml patients
Initial dose of intravenous furosemide ≥120 mg/day or 2.5 times the dose the patient was taking at home.
Conventional StrategyDrug
The dosage of loop diuretics is done according to the presence of symptoms and signs of systemic congestion and current recommendations
| Study group | Role | What they receive |
|---|---|---|
| CA125 guided strategy | Experimental | In this group loop diuretic (Furosemide) dosage will be guided by Carbohydrate Antigen 125 (CA125) plasma levels Receives: Drug: CA125 guided strategy |
| Conventional strategy | Active comparator | Standard treatment strategy Therapy is based on established european guidelines Receives: Drug: Conventional Strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in renal function (GFR)
Glomerular filtration rate (GFR) estimated by MDRD. Prespecified interim analysis of primary outcome will be made by protocol when first 100 patients are included.
Measured: 24 and 72 hours
Secondary outcomes (9)
Improvement in signs and symptoms of heart failure (NYHA)
Evaluation of dyspnea (changes in the functional class of the New York Heart Association -NYHA)
Measured: 24 and 72 hours
Improvement in signs and symptoms of heart failure (VAS)
Evaluation of signs of systemic congestion, and patient global assessment (by visual analogue scale -VAS-)
Measured: 24 and 72 hours
Changes in plasma levels of natriuretic peptide (NT-proBNP)
Measured: 72 hours
Changes in plasma levels of high sensitive troponin
Measured: 72 hours
Time required to change intravenous diuretics to oral administration.
Measured: Through study completion (30-day follow-up)
Composite of all-cause mortality plus acute heart failure related rehospitalization
Number of events in each group during 30-day follow-up
Measured: 30 days
Change in renal function (creatinin)
Serum levels of creatinine
Measured: 24 h, 72 h and 30 days
Change in renal function (urea)
Serum levels of urea
Measured: 24 h, 72 h and 30 days
Change in renal function (cystatin C)
Serum levels of Cystatin C
Measured: 24 h, 72 h and 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2015 (estimated)
- Study startJan 2015
- Primary completion30 Jan 2017
- Study completion30 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de Valencia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Julio Nuñez, Fundación para la Investigación del Hospital Clínico de Valencia
- Investigators
- Julio Nuñez, MD, PhD, Principal investigator, Fundación para la Investigación del Hospital Clínico de Valencia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02643147
- Sponsor's protocol ID
- 2014-001433-83
- Other IDs
- 2014
- Acronym
- IMPROVE-HF
- Status last verified
- Feb 2018
- First submitted
- 14 Dec 2015
- Last updated
- 13 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
de la Espriella R, Nunez E, Llacer P, Garcia-Blas S, Ventura S, Nunez JM, Sanchez R, Facila L, Vaquer JM, Bodi V, Santas E, Minana G, Mollar A, Nunez G, Chorro FJ, Gorriz JL, Sanchis J, Bayes-Genis A, Nunez J. Early urinary sodium trajectory and risk of adverse outcomes in acute heart failure and renal dysfunction. Rev Esp Cardiol (Engl Ed). 2021 Jul;74(7):616-623. doi: 10.1016/j.rec.2020.06.004. Epub 2020 Jul 2. English, Spanish.
PubMed 32624444
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Loop Diuretic Dosage in Patients With Acute Heart Failure and Renal Failure: Conventional Versus Carbohydrate Antigen 125-guided Therapy (IMPROVE-HF)
- ClinicalTrials.gov ID
- NCT02643147
- Acronym / sponsor ID
- IMPROVE-HF / 2014-001433-83
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Renal Failure, Biomarker guided-therapy, Loop diuretics, Carbohydrate antigen 125
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de ValenciaUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- 30 Jan 2017 (actual)
- Study completion
- 30 Jan 2017 (actual)
- First posted
- 31 Dec 2015 (estimated)
- 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.
Worsening renal function (WRF) is a frequent finding in patients with decompensated acute heart failure (AHF) and it is associated to increased length of hospitalization and higher morbidity and mortality. Traditionally, WRF in AHF setting has been attributed to low cardiac output, but recent evidence also suggests venous congestion play a crucial role. Loop diuretics are the mainstay treatment of AHF, but their use traditionally has been associated to WRF, but also renal function improvement in patients with unequivocal signs of congestion. Nevertheless, traditional symptoms or signs of patients with AHF have shown a limited accuracy to neither identify nor quantify the degree of venous congestion. Recent authors have reported that plasma levels of antigen carbohydrate 125 (CA125) are closely related to the degree of venous congestion.
The investigators hypothesize that CA125 may have a role for identifying the hyperhydrated (High CA125) patients that need high loop diuretic doses, and those with normal CA125 values needing low loop diuretic doses. In this randomized study (1:1) the investigators seek to evaluate whether a CA125 loop diuretic guided management therapy is superior to a standard strategy. The primary endpoint is the magnitude of changes of renal function at 24 and 72 hours after initiation of intravenous diuretic in an acute worsening of heart failure
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CA125 guided strategy | Experimental | Drug: CA125 guided strategyIn this group loop diuretic (Furosemide) dosage will be guided by Carbohydrate Antigen 125 (CA125) plasma levels |
| Conventional strategy | Active comparator | Drug: Conventional StrategyStandard treatment strategy Therapy is based on established european guidelines |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with the diagnosis of acute heart failure (AHF) and the concurrence of the following conditions:
- Presence of symptoms (dyspnea at rest or minimal exertion) and signs attributable to congestion (signs of congestion on chest radiography, or presence of peripheral edema or ascites, or jugular venous distension at 45 degrees or presence of crackles on auscultation).
- Elevated natriuretic peptide (NT-proBNP> 1000 pg/ml or BNP> 100 mg/dl).
- Creatinine ≥1,4 mg/dl on admission, provided that the estimated glomerular filtration rate less than 60 ml / min / m2.
- Intent to be treated with loop diuretics intravenously.
Key exclusion criteria (8 listed)
- Life expectancy less than 6 months of life due to other comorbid conditions.
- Cardiogenic shock.
- Diagnosis of acute coronary syndrome in the previous 30 days.
- Pregnancy at the time of inclusion.
- Restrictive or Obstructive pulmonary disease or severe degree.
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 |
|---|---|---|
| CA125 guided strategyAlso: Loop diuretic (Furosemide) dosage in CA125 ≤35 U/ml patientsInitial dose of intravenous furosemide ≤80 mg / day regardless of prior dose of loop diuretics who were receiving. | Drug | CA125 guided strategy |
| CA125 guided strategyAlso: Loop diuretic dosage (Furosemide) in CA125 >35 U/ml patientsInitial dose of intravenous furosemide ≥120 mg/day or 2.5 times the dose the patient was taking at home. | Drug | CA125 guided strategy |
| Conventional StrategyThe dosage of loop diuretics is done according to the presence of symptoms and signs of systemic congestion and current recommendations | Drug | Conventional strategy |
Primary outcome
Change in renal function (GFR)
Time frame: 24 and 72 hours
Glomerular filtration rate (GFR) estimated by MDRD. Prespecified interim analysis of primary outcome will be made by protocol when first 100 patients are included.
9 secondary outcomes
Improvement in signs and symptoms of heart failure (NYHA)
Time frame: 24 and 72 hours
Improvement in signs and symptoms of heart failure (VAS)
Time frame: 24 and 72 hours
Changes in plasma levels of natriuretic peptide (NT-proBNP)
Time frame: 72 hours
Changes in plasma levels of high sensitive troponin
Time frame: 72 hours
Time required to change intravenous diuretics to oral administration.
Time frame: Through study completion (30-day follow-up)
Composite of all-cause mortality plus acute heart failure related rehospitalization
Time frame: 30 days
Change in renal function (creatinin)
Time frame: 24 h, 72 h and 30 days
Change in renal function (urea)
Time frame: 24 h, 72 h and 30 days
Change in renal function (cystatin C)
Time frame: 24 h, 72 h and 30 days
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 13 Feb 2018.
- Derived from this study: PubMed 32624444de la Espriella R, Nunez E, Llacer P, Garcia-Blas S, Ventura S, Nunez JM, Sanchez R, Facila L, Vaquer JM, Bodi V, Santas E, Minana G, Mollar A, Nunez G, Chorro FJ, Gorriz JL, Sanchis J, Bayes-Genis A, Nunez J. Early urinary sodium trajectory and risk of adverse outcomes in acute heart failure and renal dysfunction. Rev Esp Cardiol (Engl Ed). 2021 Jul;74(7):616-623. doi: 10.1016/j.rec.2020.06.004. Epub 2020 Jul 2. English, Spanish.
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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.
Julio Nuñez, MD, PhD principal investigator
Fundación para la Investigación del Hospital Clínico de Valencia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing CA125 guided strategy and Conventional Strategy in people with Heart Failure, run by Fundación para la Investigación del Hospital Clínico de Valencia at 1 site in Spain.
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 8 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 13 Feb 2018. 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 Spain. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change in renal function (GFR) (time frame: 24 and 72 hours). 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 NCT02643147, which also lists 1 linked publication.
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 13 Feb 2018.