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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by West Virginia University Healthcare
Sponsor:
Information provided by (Responsible Party):
Courtney Brown Sweet, West Virginia University Healthcare
ClinicalTrials.gov Identifier:
NCT01721655
First received: November 1, 2012
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Chronic Lung Disease
Bronchopulmonary Dysplasia
Drug: Spironolactone
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease

Resource links provided by NLM:


Further study details as provided by West Virginia University Healthcare:

Primary Outcome Measures:
  • Dose of potassium chloride in milliequivalents/kg/day [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Requirement of electrolyte supplementation [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Treatment and control groups will be compared to assess if there is a difference between the need for electrolyte supplementation.

  • Analyze the use of furosemide rescue doses [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    The groups will be compared to assess the difference in the need for rescue furosemide doses (enteral furosemide at 2 mg/kg once daily).

  • Number of furosemide doses utilized [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    The total number of rescue furosemide doses utilized will be compared between groups.

  • Escalation in respiratory support [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Groups will be compared to determine if there is a difference in the need for an escalation in respiratory support throughout the study period. Escalation in respiratory support is defined as an increase in mean airway pressure for patients on the ventilator, 20% or greater increase in the fraction of inspired oxygen, or an escalation in the mode of support.


Estimated Enrollment: 40
Study Start Date: October 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Spironolactone
Oral spironolactone suspension dosed at 3 mg/kg/day will be administered once-daily to the patients assigned to the treatment arm.
Drug: Spironolactone
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
Other Name: Aldactone
Placebo Comparator: Placebo suspension
An oral placebo suspension dosed at 3 mg/kg/day administered once-daily will be given to patients in the placebo arm.
Drug: Placebo
Other Name: an equivalent placebo

Detailed Description:

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease (CLD), is a major complication of premature birth and is associated with significant morbidity and mortality. Bronchopulmonary dysplasia most commonly affects preterm infants who have required prolonged aggressive mechanical ventilation and/or oxygen supplementation. Risk factors associated with BPD include degree of prematurity, infection, mechanical ventilation, oxygen concentration, and nutritional status. Despite significant advances in the care of preterm infants and improved survival, the incidence of BPD has been fairly static over the past decade.

Diuretics and fluid restriction are considered a mainstay of therapy in the management of BPD to combat interstitial alveolar edema. Short courses of furosemide followed by long-term therapy using a thiazide diuretic with concurrent spironolactone have shown improvement in pulmonary function and better outcomes. Double-blinded, randomized, placebo-controlled trials have shown improvement in pulmonary compliance, airway resistance, infants alive at discharge, and a decrease in fraction of inspired oxygen and need for furosemide boluses.

Spironolactone is a competitive aldosterone receptor antagonist that acts on the distal convoluted tubule and collecting duct to facilitate sodium excretion while conserving potassium and hydrogen ions. Since only a minimal amount of sodium filtered by the glomerulus reaches the distal tubule, spironolactone is considered a weak diuretic. Spironolactone is primarily used with chlorothiazide for its potassium-sparing effect to reduce the need for electrolyte supplementation. There has only been one prospective, randomized, double-blind, placebo-controlled study comparing chlorothiazide with or without the addition of spironolactone in premature infants with chronic lung disease. This study demonstrated no difference between the groups in the need for electrolyte supplementation, electrolyte balance, or pulmonary function. In addition, preterm infants' distal tubules may respond inadequately to aldosterone; thereby, limiting the role of spironolactone in this patient population.

In the neonatal population, spironolactone is primarily used in addition with chlorothiazide for its potassium-sparing effects to reduce the need for electrolyte supplementation. However, evidence and current practice suggests the majority of patients still receive electrolyte supplementation. One study evaluated spironolactone's effect on the need for electrolyte supplementation, but there is no published data with a primary outcome evaluating spironolactone's effect on the quantity of electrolyte supplementation. We hypothesize there will be no difference in the amount of electrolyte supplementation between the two groups.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721655

Contacts
Contact: Courtney B Sweet, PharmD 304-598-4148 sweetc@wvuhealthcare.com
Contact: Leanna K Darland, PharmD 304-598-4148 darlandl@wvuhealthcare.com

Locations
United States, West Virginia
West Virginia University Healthcare Recruiting
Morgantown, West Virginia, United States, 26505
Sponsors and Collaborators
West Virginia University Healthcare
Investigators
Principal Investigator: Courtney B Sweet, PharmD WVU Healthcare
  More Information

Publications:

Responsible Party: Courtney Brown Sweet, Pediatric Clinical Pharmacy Specialist, West Virginia University Healthcare
ClinicalTrials.gov Identifier: NCT01721655     History of Changes
Other Study ID Numbers: H-24305
Study First Received: November 1, 2012
Last Updated: June 2, 2014
Health Authority: United States: West Virginia University Healthcare Institutional Review Board

Keywords provided by West Virginia University Healthcare:
Spironolactone
Preterm Infants
Chronic Lung Disease
Bronchopulmonary Dysplasia
Electrolyte Supplementation

Additional relevant MeSH terms:
Bronchopulmonary Dysplasia
Lung Diseases
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Injury
Respiratory Tract Diseases
Ventilator-Induced Lung Injury
Spironolactone
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014