Clinical trial NCT02643147: Loop Diuretic Dosage in Patients With Acute Heart Failure and Renal Failure: Conventional Versus Carbohydrate Antigen 125-guided Therapy (IMPROVE-HF)
Official title: Loop Diuretic Dosage in Patients With Acute Heart Failure and Renal Failure: Conventional Versus Carbohydrate Antigen 125-guided Therapy (IMPROVE-HF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Heart Failure
Renal Failure
Biomarker guided-therapy
Loop diuretics
Carbohydrate antigen 125
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
First posted: 2015-12-31
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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


Eligibility criteria: Inclusion Criteria:

Patients with the diagnosis of acute heart failure (AHF) and the concurrence of the following conditions:

1. 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).
2. Elevated natriuretic peptide (NT-proBNP\> 1000 pg/ml or BNP\> 100 mg/dl).
3. Creatinine ≥1,4 mg/dl on admission, provided that the estimated glomerular filtration rate less than 60 ml / min / m2.
4. Intent to be treated with loop diuretics intravenously.

Exclusion Criteria:

1. Life expectancy less than 6 months of life due to other comorbid conditions.
2. Cardiogenic shock.
3. Diagnosis of acute coronary syndrome in the previous 30 days.
4. Pregnancy at the time of inclusion.
5. Restrictive or Obstructive pulmonary disease or severe degree.
6. Chronic renal insufficiency in stage V (estimated glomerular filtration rate \<15 ml / min / m2) or patient previously included in known dialysis program.
7. Participation in another clinical trial randomized at the time of inclusion.
8. Temperature ≥38 ° C or diagnosis of pneumonia.

Primary outcomes:
measure: Change in renal function (GFR)
timeFrame: 24 and 72 hours
Secondary outcomes:
measure: Improvement in signs and symptoms of heart failure (NYHA)
timeFrame: 24 and 72 hours
measure: Improvement in signs and symptoms of heart failure (VAS)
timeFrame: 24 and 72 hours
measure: Changes in plasma levels of natriuretic peptide (NT-proBNP)
timeFrame: 72 hours
measure: Changes in plasma levels of high sensitive troponin
timeFrame: 72 hours
measure: Time required to change intravenous diuretics to oral administration.
timeFrame: Through study completion (30-day follow-up)
measure: Composite of all-cause mortality plus acute heart failure related rehospitalization
timeFrame: 30 days
measure: Change in renal function (creatinin)
timeFrame: 24 h, 72 h and 30 days
measure: Change in renal function (urea)
timeFrame: 24 h, 72 h and 30 days
measure: Change in renal function (cystatin C)
timeFrame: 24 h, 72 h and 30 days
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Fundación para la Investigación del Hospital Clínico de Valencia
name: Julio Nuñez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.