Clinical trial NCT01721655: Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease
Official title: Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Chronic Lung Disease
Bronchopulmonary Dysplasia
Keywords: Spironolactone
Preterm Infants
Chronic Lung Disease
Bronchopulmonary Dysplasia
Electrolyte Supplementation
Lead sponsor: West Virginia University Healthcare
Sponsor class: OTHER
First posted: 2012-11-06
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Dose of potassium chloride in milliequivalents/kg/day
timeFrame: Day 28
Secondary outcomes:
measure: Requirement of electrolyte supplementation
timeFrame: Day 28
measure: Analyze the use of furosemide rescue doses
timeFrame: Day 28
measure: Number of furosemide doses utilized
timeFrame: Day 28
measure: Escalation in respiratory support
timeFrame: Day 28
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
Study officials:
affiliation: WVU Healthcare
name: Courtney B Sweet, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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