Clinical trial NCT01441245: Loop Diuretics Administration and Acute Heart Failure
Official title: Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Heart Failure
Keywords: acute heart failure
diuretics
BNP
Renal function
acute decompensated Heart Failure,
volume overload
Lead sponsor: University of Siena
Sponsor class: OTHER
First posted: 2011-09-27
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Intravenous loop diuretics is the therapy most commonly used to treat pulmonary congestion and systemic fluid overload. In theory, continuous infusion should allow for a more consistent diuresis, avoiding the sodium reabsorption in the distal tubule as well as the neurohormonal activation. This should lead to renal function improvement and BNP decrease.

Detailed description: Patients were eligible if they were admitted with a primary diagnosis of ADHF, randomized within 12 h after hospital presentation, and with evidence of volume overload (pulmonary congestion) on a chest X-ray study and had BNP levels \>100 pg/ml. Patients also displayed mild to moderate renal dysfunction with creatinine values up to 1.4 mg/dl. Some patients were supported with non invasive ventilation before randomization. Once the initial 12 h dose was determined, patients were randomized using a 1:1 ratio using a computer-generated scheme to receive the furosemide dose either divided into a twice-daily bolus injection or in a continuous infusion (mixed as a 1:1 ratio in 5 % dextrose in water) for a time period ranging from 72 to 120 h. The randomization was casual, and the physicians did not previously know the assigned arm. The dose escalation and subsequent titration of furosemide was guided by clinical response in terms of urine output volume and body weight reduction .Before randomization, renal function parameters and BNP levels were measured in all patients. Subsequent titration of the furosemide dosage was at the discretion of the attending physician, but was guided by a dose-escalation algorithm based on the treatment response (weight loss and urine output volume), symptom improvement, changes in renal function, electrolyte balance, and chest radiography. The specific doses of furosemide and the use of additional agents to manage ADHF (dopamine, IV vasodilators, hypertonic saline infusion) were decided based upon blood pressure measurements, renal function evaluation and diuresis response. Supplementary treatment was left to the discretion of the treating physician. The duration of infusion was continued for up to 72 h, at 48 h the physicians had the possibility to adjust diuretic dose administration on the basis of the clinical response. After 72 h the treatment could be stopped or continued for an additional 36-48 h depending on the patient's condition and diuresis response. Acute kidney injury (AKI) was defined following the RIFLE criteria.

Abbreviations:

(AKI) Acute kidney injury (ADHF) Acute decompensated heart failure (BNP) B-type natriuretic peptide (CHD) Coronary heart disease (cIV) Continuous infusion (iIV) Intermittent infusione (eGFR)Estimated glomerular filtration rate (Hb) Hemoglobin (HF) Heart failure (Hct) Hematocrit (LVEF) Left ventricular ejection fraction (RBC) Red blood cells

Eligibility criteria: Inclusion Criteria:

* Patients took part in the random sample selection if they met the diagnostic criteria for acute decompensated HF.
* Patients with primary diagnosis of ADHF, volume overload with cardia dilation and LVEF \<50%, and had BNP levels \>100 pg/ml.

Exclusion Criteria:

* Patients were excluded if they had received more than 2 IV doses of furosemide or any continuous infusion of furosemide 1 month before randomization
* If they had end-stage renal disease or the need for renal replacement therapy, isolated diastolic dysfunction.
* Recent myocardial infarction

Primary outcomes:
measure: Evaluation of Mean Urine Output Volume During the Infusion Period
timeFrame: time period ranging from 72 h to 120 h.
measure: Evaluation of Renal Function in Terms of Creatinine Levels at Discharge
timeFrame: from admission to discharge, an average of 12 days
measure: Evaluation of Renal Function in Terms of Changes in Creatinine Levels
timeFrame: participants were followed for the duration of hospital stay, an average of 13 days
measure: Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment
timeFrame: from admission to discharge, an average of 12 days
measure: Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge
timeFrame: participants were followed for the duration of hospital stay, an average of 13 days
measure: Evaluation of Renal Function in Terms of Changes in GFR
timeFrame: from admission to discharge, an average of 12 days
measure: Evaluation of Renal Function in Terms of GFR Values at Discharge
timeFrame: from admission to discharge, an average of 12 days
Secondary outcomes:
measure: Length of Hospitalization in the Two Groups
timeFrame: in-hospital
measure: Dopamine Infusion During Hospitalization
timeFrame: in-hospital
Other outcomes:
Locations:
city: Siena,
country: Italy
facility: Department of Internal Medicine, Cardiology Section Center
Study officials:
affiliation: Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital, Siena
name: Alberto Palazzuoli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Palazzuoli A, Pellegrini M, Franci B, Beltrami M, Ruocco G, Gonnelli S, Angelini GD, Nuti R. Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction. Intern Emerg Med. 2015 Feb;10(1):41-9. doi: 10.1007/s11739-014-1112-5. Epub 2014 Aug 3.
citation: Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
citation: Ruocco G, Feola M, Nuti R, Luschi L, Evangelista I, Palazzuoli A. Loop Diuretic Administration in Patients with Acute Heart Failure and Reduced Systolic Function: Effects of Different Intravenous Diuretic Doses and Diuretic Response Measurements. J Clin Med. 2019 Nov 2;8(11):1854. doi: 10.3390/jcm8111854.
citation: Ruocco G, Evangelista I, Franci B, Lucani B, Martini S, Nuti R, Palazzuoli A. Combination of ST2 and B-type natriuretic peptide in diabetic patients with acute heart failure: relation with ventricular stiffness and outcome. J Cardiovasc Med (Hagerstown). 2019 Feb;20(2):81-90. doi: 10.2459/JCM.0000000000000741.
citation: Palazzuoli A, Pellegrini M, Ruocco G, Martini G, Franci B, Campagna MS, Gilleman M, Nuti R, McCullough PA, Ronco C. Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial. Crit Care. 2014 Jun 28;18(3):R134. doi: 10.1186/cc13952.