Loop Diuretics Administration and Acute Heart Failure

NCT ID: NCT01441245

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2017-12-28

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

Conditions

Acute Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Continuous furosemide infusion

The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients;

Group Type: EXPERIMENTAL

furosemide infusion

Intervention Type: DRUG

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

Intermittent furosemide infusion

The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients

Group Type: EXPERIMENTAL

furosemide infusion

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Continuous vs intermittent intravenous furosemide infusion

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Siena

OTHER

Sponsor Role: lead

Responsible Party

Alberto Palazzuoli MD PhD

Consultant cardiologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alberto Palazzuoli, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital, Siena

Locations

Department of Internal Medicine, Cardiology Section Center

Siena, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 25087085 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21366472 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31684094 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30540645 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24974232 (View on PubMed)

Other Identifiers

diuretic1

Identifier Type: -

Identifier Source: org_study_id