Loop Diuretics Administration and Acute Heart Failure (diurHF)

• ClinicalTrials.gov Identifier: NCT01441245
• Recruitment Status: Completed
• First Posted: September 27, 2011
• Results First Posted: February 2, 2016
• Last Update Posted: January 23, 2018
• Sponsor: University of Siena
• Information provided by (Responsible Party): Alberto Palazzuoli MD PhD, University of Siena

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Heart Failure	Drug: furosemide infusion	Phase 4

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels
• Actual Study Start Date: April 2010
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: December 28, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Continuous furosemide infusion; The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients;	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; Other Name: Continuous vs intermittent intravenous furosemide infusion
Experimental: Intermittent furosemide infusion; The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients	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; Other Name: Continuous vs intermittent intravenous furosemide infusion

Outcome Measures

Primary Outcome Measures :

1. Evaluation of Mean Urine Output Volume During the Infusion Period [ Time Frame: time period ranging from 72 h to 120 h. ]
   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
2. Evaluation of Renal Function in Terms of Creatinine Levels at Discharge [ Time Frame: from admission to discharge, an average of 12 days ]
3. Evaluation of Renal Function in Terms of Changes in Creatinine Levels [ Time Frame: participants were followed for the duration of hospital stay, an average of 13 days ]
   evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms.
4. Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment [ Time Frame: from admission to discharge, an average of 12 days ]
5. Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge [ Time Frame: participants were followed for the duration of hospital stay, an average of 13 days ]
6. Evaluation of Renal Function in Terms of Changes in GFR [ Time Frame: from admission to discharge, an average of 12 days ]
7. Evaluation of Renal Function in Terms of GFR Values at Discharge [ Time Frame: from admission to discharge, an average of 12 days ]

Secondary Outcome Measures :

1. Length of Hospitalization in the Two Groups [ Time Frame: in-hospital ]
   percentage of participants with hospital stay > 10 days
2. Dopamine Infusion During Hospitalization [ Time Frame: in-hospital ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

Department of Internal Medicine, Cardiology Section Center

Siena,, Italy, 53100

Sponsors and Collaborators

University of Siena

Investigators

• Principal Investigator: Alberto Palazzuoli, MD; Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital, Siena

More Information

Publications of Results:

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.

Other Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). pii: E1854. doi: 10.3390/jcm8111854.

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.

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.

• Responsible Party: Alberto Palazzuoli MD PhD, Consultant cardiologist, University of Siena
• ClinicalTrials.gov Identifier: NCT01441245
• Other Study ID Numbers: diuretic1
• First Posted: September 27, 2011
• Results First Posted: February 2, 2016
• Last Update Posted: January 23, 2018
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Alberto Palazzuoli MD PhD, University of Siena:

acute heart failure; diuretics; BNP; Renal function; acute decompensated Heart Failure,; volume overload

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases; Furosemide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action