Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease

NCT01721655 | Unknown Phase 2

• 1 other identifier: H-24305
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease (CLD), is a major complication of premature birth and is associated with a significant increased risk of complications including death. Diuretics have been used for decades in babies with BPD and are considered a standard of care. Patients receive electrolyte supplementation to replace the electrolytes removed by the diuretics. Spironolactone is not as good as other diuretics at removing extra fluid, but it is different from chlorothiazide and furosemide because instead of removing potassium, it actually can increase potassium levels in our body. Spironolactone is used with chlorothiazide to try to minimize the potassium lost; therefore, reduce the electrolyte supplementation needed. However, studies have suggested that preterm babies aren´t developed enough to appropriately respond to spironolactone. Also, one study has shown that adding spironolactone to chlorothiazide in patients with BPD has no effect on whether or not patients receive electrolyte supplementation. This study will examine whether there is a difference in the amount of electrolyte supplementation between patients receiving chlorothiazide only or chlorothiazide plus spironolactone. the investigators hypothesize there will be no difference in the amount of electrolyte supplementation between the two groups.

Conditions

Chronic Lung Disease; Bronchopulmonary Dysplasia

Keywords

Spironolactone; Preterm Infants; Chronic Lung Disease; Bronchopulmonary Dysplasia; Electrolyte Supplementation

Outcome Measures

Primary Outcomes (1)

• Dose of potassium chloride in milliequivalents/kg/day

  The primary objective of this study is to assess the effect of spironolactone on the quantity of electrolyte supplementation in preterm infants receiving a standard regimen for chronic lung disease. The primary endpoint compared between groups will be the dose of potassium chloride in milliequivalents/kg/day from baseline to day 28.

  Day 28

Secondary Outcomes (4)

• Requirement of electrolyte supplementation

  Day 28

• Analyze the use of furosemide rescue doses

  Day 28

• Number of furosemide doses utilized

  Day 28

• Escalation in respiratory support

  Day 28

Study Arms (2)

Spironolactone

ACTIVE COMPARATOR

Oral spironolactone suspension dosed at 3 mg/kg/day will be administered once-daily to the patients assigned to the treatment arm.

Drug: Spironolactone

Placebo suspension

PLACEBO COMPARATOR

An oral placebo suspension dosed at 3 mg/kg/day administered once-daily will be given to patients in the placebo arm.

Drug: Placebo

Interventions

Spironolactone DRUG

Patients will continue to receive standard of care as if they were not enrolled in the study. All patients will receive oral chlorothiazide 40 mg/kg/day divided twice-daily, electrolyte supplementation as needed based on a standard algorithm, and if needed, rescue enteral furosemide 2 mg/kg/day. The intervention will be enteral spironolactone 3 mg/kg once daily

Also known as: Aldactone

Spironolactone

Placebo DRUG

Patients will continue to receive standard of care as if they were not enrolled in the study. All patients will receive oral chlorothiazide 40 mg/kg/day divided twice-daily, electrolyte supplementation as needed based on a standard algorithm, and if needed, rescue enteral furosemide 2 mg/kg/day.

Also known as: an equivalent placebo

Placebo suspension

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The attending makes the decision to start enteral chlorothiazide for long-term diuretic therapy.
• Gestational age \< 32 weeks at time of delivery
• If patient is currently receiving furosemide and electrolyte supplements, these must be discontinued prior to enrollment.

You may not qualify if:

• Renal anomaly
• Receiving maintenance IV fluids for more than the previous 48 hours
• Any contraindication to receiving enteral medication
• Serum Na \< 132 mEq/L
• Serum K \< 3.0 mEq/L
• Serum Cl \< 92 mEq/L
• Presence of ostomy of any sort

Sponsors & Collaborators

• West Virginia University Healthcare: lead

Study Sites (1)

West Virginia University Healthcare

Morgantown, West Virginia, 26505, United States

RECRUITING

Related Publications (19)

• Jeng SF, Hsu CH, Tsao PN, Chou HC, Lee WT, Kao HA, Hung HY, Chang JH, Chiu NC, Hsieh WS. Bronchopulmonary dysplasia predicts adverse developmental and clinical outcomes in very-low-birthweight infants. Dev Med Child Neurol. 2008 Jan;50(1):51-7. doi: 10.1111/j.1469-8749.2007.02011.x.

  PMID: 18173631 BACKGROUND

• Gien J, Kinsella JP. Pathogenesis and treatment of bronchopulmonary dysplasia. Curr Opin Pediatr. 2011 Jun;23(3):305-13. doi: 10.1097/MOP.0b013e328346577f.

  PMID: 21494147 BACKGROUND

• Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.

  PMID: 11401896 BACKGROUND

• Smith VC, Zupancic JA, McCormick MC, Croen LA, Greene J, Escobar GJ, Richardson DK. Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002. J Pediatr. 2005 Apr;146(4):469-73. doi: 10.1016/j.jpeds.2004.12.023.

  PMID: 15812448 BACKGROUND

• Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967 Feb 16;276(7):357-68. doi: 10.1056/NEJM196702162760701. No abstract available.

  PMID: 5334613 BACKGROUND

• Jobe AH, Ikegami M. Mechanisms initiating lung injury in the preterm. Early Hum Dev. 1998 Nov;53(1):81-94. doi: 10.1016/s0378-3782(98)00045-0.

  PMID: 10193929 BACKGROUND

• Jobe AJ. The new BPD: an arrest of lung development. Pediatr Res. 1999 Dec;46(6):641-3. doi: 10.1203/00006450-199912000-00007. No abstract available.

  PMID: 10590017 BACKGROUND

• Shah PS. Current perspectives on the prevention and management of chronic lung disease in preterm infants. Paediatr Drugs. 2003;5(7):463-80. doi: 10.2165/00128072-200305070-00004.

  PMID: 12837119 BACKGROUND

• Tropea K, Christou H. Current pharmacologic approaches for prevention and treatment of bronchopulmonary dysplasia. Int J Pediatr. 2012;2012:598606. doi: 10.1155/2012/598606. Epub 2012 Jan 3.

  PMID: 22262977 BACKGROUND

• Biniwale MA, Ehrenkranz RA. The role of nutrition in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol. 2006 Aug;30(4):200-8. doi: 10.1053/j.semperi.2006.05.007.

  PMID: 16860160 BACKGROUND

• Albersheim SG, Solimano AJ, Sharma AK, Smyth JA, Rotschild A, Wood BJ, Sheps SB. Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia. J Pediatr. 1989 Oct;115(4):615-20. doi: 10.1016/s0022-3476(89)80297-5.

  PMID: 2677293 BACKGROUND

• Kao LC, Durand DJ, McCrea RC, Birch M, Powers RJ, Nickerson BG. Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia. J Pediatr. 1994 May;124(5 Pt 1):772-81. doi: 10.1016/s0022-3476(05)81373-3.

  PMID: 8176568 BACKGROUND

• Kao LC, Warburton D, Cheng MH, Cedeno C, Platzker AC, Keens TG. Effect of oral diuretics on pulmonary mechanics in infants with chronic bronchopulmonary dysplasia: results of a double-blind crossover sequential trial. Pediatrics. 1984 Jul;74(1):37-44.

  PMID: 6377221 BACKGROUND

• Engelhardt B, Blalock WA, DonLevy S, Rush M, Hazinski TA. Effect of spironolactone-hydrochlorothiazide on lung function in infants with chronic bronchopulmonary dysplasia. J Pediatr. 1989 Apr;114(4 Pt 1):619-24. doi: 10.1016/s0022-3476(89)80708-5.

  PMID: 2926575 BACKGROUND

• Brion LP, Primhak RA, Ambrosio-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2002;(1):CD001817. doi: 10.1002/14651858.CD001817.

  PMID: 11869608 BACKGROUND

• Segar JL. Neonatal diuretic therapy: furosemide, thiazides, and spironolactone. Clin Perinatol. 2012 Mar;39(1):209-20. doi: 10.1016/j.clp.2011.12.007. Epub 2011 Dec 29.

  PMID: 22341547 BACKGROUND

• Hoffman DJ, Gerdes JS, Abbasi S. Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled, randomized trial. J Perinatol. 2000 Jan-Feb;20(1):41-5. doi: 10.1038/sj.jp.7200307.

  PMID: 10693099 BACKGROUND

• Sulyok E, Varga F, Gyory E, Jobst K, Csaba IF. Postnatal development of renal sodium handling in premature infants. J Pediatr. 1979 Nov;95(5 Pt 1):787-92. doi: 10.1016/s0022-3476(79)80737-4.

  PMID: 490250 BACKGROUND

• Spitzer A. The role of the kidney in sodium homeostasis during maturation. Kidney Int. 1982 Apr;21(4):539-45. doi: 10.1038/ki.1982.60.

  PMID: 7047859 BACKGROUND

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Courtney B Sweet, PharmD

  WVU Healthcare

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney B Sweet, PharmD

CONTACT

304-598-4148; sweetc@wvuhealthcare.com

Leanna K Darland, PharmD

CONTACT

304-598-4148; darlandl@wvuhealthcare.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Clinical Pharmacy Specialist

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 6, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 30, 2016

Record last verified: 2016-11

Locations

US (1)