Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01721655|
Recruitment Status : Recruiting
First Posted : November 6, 2012
Last Update Posted : November 30, 2016
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lung Disease Bronchopulmonary Dysplasia||Drug: Spironolactone Drug: Placebo||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Care Provider, Investigator)|
|Official Title:||Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease|
|Study Start Date :||October 2012|
|Estimated Primary Completion Date :||December 2016|
|Estimated Study Completion Date :||December 2016|
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.
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.
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.
Other Name: an equivalent placebo
- Dose of potassium chloride in milliequivalents/kg/day [ Time Frame: Day 28 ]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.
- Requirement of electrolyte supplementation [ Time Frame: Day 28 ]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 ]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 ]The total number of rescue furosemide doses utilized will be compared between groups.
- Escalation in respiratory support [ Time Frame: Day 28 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01721655
|Contact: Courtney B Sweet, PharmDfirstname.lastname@example.org|
|Contact: Leanna K Darland, PharmDemail@example.com|
|United States, West Virginia|
|West Virginia University Healthcare||Recruiting|
|Morgantown, West Virginia, United States, 26505|
|Principal Investigator:||Courtney B Sweet, PharmD||WVU Healthcare|