Furosemide Versus Ethacrynic Acid in Children With Congenital Heart Disease

Overview

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.

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

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: July 2013

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.

Interventions

• Drug: furosemide
  • furosemide, intravenous, continuous infusion, 0.2 mg/kg/h for 24 hours
• Drug: ethacrynic acid
  • ethacrynic acid, intravenous, continuous infusion, 0.2 mg/kg/h for 24 hours

Arms, Groups and Cohorts

• Active Comparator: furosemide
  • furosemide, 0.2 mg/kg/h up to 0.8 mg/kg/h for 72 hours
• Active Comparator: ethacryinic acid
  • ethacrynic acid, 0.2 mg/kg/h up to 0.8 mg/kg/h for 72 hours

Clinical Trial Outcome Measures

Primary Measures

• Mean total urine output production in the first post-operative day
  • Time Frame: first 24 hours after Intensive Care Unit admission
  • 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

Secondary Measures

• Mean creatinine and NGAL values
  • Time Frame: first 72 hours after Intensive Care Unit admission
  • 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: 10 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Bambino Gesù Hospital and Research Institute
• Provider of Information About this Clinical Study
  • Principal Investigator: Zaccaria Ricci, Medical Doctor, Research Fellow – Bambino Gesù Hospital and Research Institute
• Overall Official(s)
  • Zaccaria Ricci, MD, Principal Investigator, Bambino Gesù Hospital RI

References

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.