Phase I, Placebo-Controlled, Blinded Pilot Study of Ipratropium in Children Admitted to the ICU With Status Asthmaticus

Phase I, Placebo-Controlled, Blinded Pilot Study of Ipratropium in Children Admitted to the ICU With Status Asthmaticus

A Phase I, Single Center, Placebo-Controlled, Blinded Pilot Study of Ipratropium Bromide in Children Admitted to the Intensive Care Unit With Status Asthmaticus

This study is a Phase I study to investigate the addition of inhaled Ipratropium bromide to standard therapy in the treatment of severe asthma attacks in children admitted to the Pediatric Intensive Care Unit. Half of the subjects will receive inhaled Ipratropium, and half will receive an inhaled placebo.

Status asthmaticus is an acute exacerbation of asthma that often requires treatment in a pediatric intensive care unit (PICU). Standard therapies for status asthmaticus include corticosteroids and bronchodilators, typically albuterol. Ipratropium bromide is also a bronchodilator, but has a different mechanism of action than albuterol. The addition of Ipraropium to children in the Emergency Room with severe asthma exacerbations improves outcomes, so many PICU doctors treat patients with status asthmaticus with Ipratropium. However, two studies of children hospitalized in the general wards of the hospital (not the PICU) show that the addition of Ipratropium to standard care does not effect clinical outcomes. This study is a first step towards determining in Ipratropium is helpful in PICU patients (like it is in ER patients) or if it not helpful (like it is in general ward patients).

systemic (IV or enteral) corticosteroid prescribed by the clinical team, typically methylprednisolone IV

In our PICU, status asthmaticus patients are initially treated with continuous nebulization of albuterol. Per a standard assessment/scoring system, the patients are re-assessed each hour. When the patient's symptoms have sufficiently improved, the albuterol is weaned to 2.5mg given every 1hr ("q1hr albuterol") and, subsequently, to 2.5mg given every 2 hours ("q2hr Albuterol"). This outcome will measure the interval between the initiation of continuous albuterol and the second dose of q2hr Albuterol.

The time interval between admission to the PICU and discharge from the PICU, typically to the general ward. Patients are typically transferred to the general ward when they are receiving albuterol every 3 hours.

The time interval between admission to the hospital and discharge from the hospital. Patients are typically discharged from the hospital when they are receiving albuterol every 4 hours.

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Adverse effects will be assessed 4-6hrs after each administration of study drug (and prior to the next administration of study drug)

Inclusion Criteria: Admission to the PICU Treatment with continuous albuterol via the Asthma Carepath Enrollment occurred within 4 hours of starting continuous albuterol in the PICU Treatment with systemic corticosteroids by the clinical team Exclusion Criteria: First episode of wheezing that prompted treatment with bronchodilators by medical personnel Prior enrollment in this study Patients with chronic lung disease requiring routine home oxygen use Allergy to inhaled ipratropium or inhaled saline Positive pressure ventilation (via an endotracheal tube or a non-invasive mask [e.g. CPAP (continuous positive airway pressure) or BiPAP]) Pregnancy Tracheostomy Age < 2 years Age > 17 years Patient with pulmonary hypertension requiring daily therapy Patient with cyanotic congenital heart disease Cystic fibrosis

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Biagini Myers JM, Simmons JM, Kercsmar CM, Martin LJ, Pilipenko VV, Austin SR, Lindsey MA, Amalfitano KM, Guilbert TW, McCoy KS, Forbis SG, McBride JT, Ross KR, Vauthy PA, Khurana Hershey GK. Heterogeneity in asthma care in a statewide collaborative: the Ohio Pediatric Asthma Repository. Pediatrics. 2015 Feb;135(2):271-9. doi: 10.1542/peds.2014-2230. Epub 2015 Jan 19.