Loop Diuretics Administration and Acute Heart Failure

Acute Heart Failure Clinical Trial

— diurHF  

Official title:

Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01441245
• Other study ID #: diuretic1
• Status: Completed
• Phase: Phase 4
• First received: September 22, 2011
• Last updated: December 28, 2017
• Start date: April 2010
• Est. completion date: December 28, 2017

Study information

• Verified date: December 2017
• Source: University of Siena
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: December 28, 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

Drug:
• furosemide infusion
Patients were randomized in a 1:1 ratio to receive furosemide dose divided into twice-daily bolus injection (group 0) or continuous infusion (group 1)(mixed as a 1:1 ratio in 5% dextrose in water) for a time period ranging from 72 to 120 hours. The mean daily diuretic dosage was similar in the two groups. The median time from presentation to randomization was 16 hours, and the median duration of study-drug administration was 112± 24 hours

Locations

Country	Name	City	State
Italy	Department of Internal Medicine, Cardiology Section Center	Siena,

Sponsors (1)

Lead Sponsor	Collaborator
University of Siena

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of Mean Urine Output Volume During the Infusion Period	this study aimed to evaluate the effects of continuous infusion of furosemide in comparison to twice daily regimens at similar doses with respect to changes in renal function in terms of creatinine levels and GFR, urine output and BNP levels from admission to discharge	time period ranging from 72 h to 120 h.
Primary	Evaluation of Renal Function in Terms of Creatinine Levels at Discharge		from admission to discharge, an average of 12 days
Primary	Evaluation of Renal Function in Terms of Changes in Creatinine Levels	evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms.	participants were followed for the duration of hospital stay, an average of 13 days
Primary	Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment		from admission to discharge, an average of 12 days
Primary	Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge		participants were followed for the duration of hospital stay, an average of 13 days
Primary	Evaluation of Renal Function in Terms of Changes in GFR		from admission to discharge, an average of 12 days
Primary	Evaluation of Renal Function in Terms of GFR Values at Discharge		from admission to discharge, an average of 12 days
Secondary	Length of Hospitalization in the Two Groups	percentage of participants with hospital stay > 10 days	in-hospital
Secondary	Dopamine Infusion During Hospitalization		in-hospital