Furosemide Versus Ethacrynic Acid in Children With Congenital Heart Disease

Phase III Study of Furosemide Continuous Infusion Versus Ethacrynic Acid Continuous Infusion in Children Undergoing Cardiac Surgery: Randomized Double Blind Controlled Clinical Trial

This study aims to verify if ethacrynic acid continuous infusion is superior to furosemide continuous infusion in total urine output production during the first 24 post operative hours.

Study Overview

• Status: Completed
• Conditions: Fluid Overload
• Intervention / Treatment: Drug: furosemide; Drug: ethacrynic acid

Detailed Description

Diuretic therapy in children after open heart surgery is widely administered, though no evidence currently supports if an ideal drug or an ideal dosage can be recommended. Loop diuretics are the most effective drugs in terms of urine output production but may cause some collateral effects such as metabolic alkalosis, hypovolemia, hypokalemia, ototoxicity. Furthermore, some reports showed that loop diuretics usage can be associated with an increased risk of renal dysfunction and mortality. However, their use in children with signs of fluid overload, pulmonary edema or oliguria is mandatory and widely practiced.

Furosemide and ethacrynic acid are often prescribed and administered without any specific indication, basing on clinicians preferences.

No study so far, explored the hypothesis of which of these drugs is the most effective in terms of urine output production and safe in terms of renal function.

This study aims to verify if ethacrynic acid continuous infusion is superior to furosemide continuous infusion in total urine output production during the first 24 post operative hours.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00165
    • Bambino Gesu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children with congenital heart disease undergoing cardiac surgery
• intraoperative aortic cross clamp over 90 minutes or interventional catheterization procedures with post-operative inotrope score over 20
• sign of fluid retention after surgical procedures

Exclusion Criteria:

• Preoperative renal dysfunction
• Preoperative administration of more than 4mg/kg/die loop diuretics
• Need for renal replacement therapy at ICU admission
• Need for ECMO at ICU admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: furosemide; furosemide, 0.2 mg/kg/h up to 0.8 mg/kg/h for 72 hours	Drug: furosemide; furosemide, intravenous, continuous infusion, 0.2 mg/kg/h for 24 hours; Other Names: lasix
Active Comparator: ethacryinic acid; ethacrynic acid, 0.2 mg/kg/h up to 0.8 mg/kg/h for 72 hours	Drug: ethacrynic acid; ethacrynic acid, intravenous, continuous infusion, 0.2 mg/kg/h for 24 hours; Other Names: reomax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean total urine output production in the first post-operative day	Verification of the superiority of ethacrynic acid compared with furosemide in improving patients' total urine output by at least 1 ml/kg/h in the first 24 post-operative hours	first 24 hours after Intensive Care Unit admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean creatinine and NGAL values	Verification of the superiority of ethacrynic acid compared with furosemide in improving patients' renal function (asessed as creatinine, NGAL and pRIFLE score) in the first 72 post-operative hours	first 72 hours after Intensive Care Unit admission

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute
• Investigators: Principal Investigator: Zaccaria Ricci, MD, Bambino Gesù Hospital RI

Publications and helpful links

General Publications

• Klinge JM, Scharf J, Hofbeck M, Gerling S, Bonakdar S, Singer H. Intermittent administration of furosemide versus continuous infusion in the postoperative management of children following open heart surgery. Intensive Care Med. 1997 Jun;23(6):693-7. doi: 10.1007/s001340050395.
• van der Vorst MM, Ruys-Dudok van Heel I, Kist-van Holthe JE, den Hartigh J, Schoemaker RC, Cohen AF, Burggraaf J. Continuous intravenous furosemide in haemodynamically unstable children after cardiac surgery. Intensive Care Med. 2001 Apr;27(4):711-5. doi: 10.1007/s001340000819.
• Bagshaw SM, Gibney RT, McAlister FA, Bellomo R. The SPARK Study: a phase II randomized blinded controlled trial of the effect of furosemide in critically ill patients with early acute kidney injury. Trials. 2010 May 11;11:50. doi: 10.1186/1745-6215-11-50.
• Ricci Z, Haiberger R, Pezzella C, Garisto C, Favia I, Cogo P. Furosemide versus ethacrynic acid in pediatric patients undergoing cardiac surgery: a randomized controlled trial. Crit Care. 2015 Jan 7;19(1):2. doi: 10.1186/s13054-014-0724-5.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: June 24, 2012
• First Submitted That Met QC Criteria: June 26, 2012
• First Posted (Estimate): June 27, 2012

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: fluid balance; loop diuretics; urine output; acute renal dysfunction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Ethacrynic Acid
• Other Study ID Numbers: FUROCRYNIC trial-1; OBG DIURETICS (Other Identifier: Bambino Gesù Hospital RI)