The Childhood Asthma Management Program (CAMP)

Abstract

The Childhood Asthma Management Program (CAMP) is a multicenter, randomized, double-masked clinical trial designed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma: budesonide (a glucocorticoid used daily) and albuterol (a short-acting β-agonist bronchodilator used as needed); nedocromil (a nonsteroid anti-inflammatory agent used daily) and albuterol; and placebo and albuterol. One thousand forty-one children (32% from ethnic minority groups), aged 5 to 12 years at screening, are currently participating. The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second (FEV₁) percent of predicted, observed over 5- to 6-year period. The trial also assesses differences between treatment groups with respect to airway responsiveness, morbidity, physical growth and development, and psychological growth and development. This report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial.

Introduction

Asthma, the most common chronic respiratory disease of childhood, is characterized by airway obstruction that is at least partially reversible, by airway inflammation, and by increased airway responsiveness to a variety of stimuli [1]. Ten million children under the age of 16 in the United States have asthma [2]. Both its prevalence and the frequency of hospitalizations it necessitates are increasing among children 3, 4, 5. Asthma appears to have a strong inverse effect on lung growth in childhood [6]. The maximal level of lung function attained in early adulthood may be an important predictor of the rate of decline of lung function [7], which, in turn, may lead to the development of chronic obstructive lung disease.

Therapy for asthma focuses on prevention and/or treatment of airway inflammation, as well as relief of symptoms. Studies have found inhaled corticosteroids to relieve bronchial responsiveness and increase lung function 8, 9, 10. Nonsteroid anti-inflammatory medications have also been found effective in a substantial proportion of patients 11, 12, 13. Bronchodilators (such as inhaled β-agonists, inhaled anticholinergic agents, and oral theophylline) work quickly to relieve symptoms by relaxing the smooth muscles in the walls of the airways. Asthma episodes that do not respond sufficiently to bronchodilators may be treated with short courses (several days) of oral steroids. Concerns remain, however, about the long-term use of steroids in children, as they may decrease or delay somatic growth and sexual and bone maturation 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. Repeated use of oral steroids to control acute exacerbations carries other side effects, such as adrenal suppression, osteoporosis, and cataracts 26, 27, 28.

The concerns about side effects, uncertainty about the relative effectiveness of steroid versus nonsteroid antiasthma medication, and questions about the need for chronic medication for mild asthma pose a dilemma for clinicians. With these issues in mind, the National Heart, Lung, and Blood Institute (NHLBI) released a Request for Proposal (RFP) for the Childhood Asthma Management Program (CAMP) in November 1990. The RFP called for proposals for a trial comparing regular use of two classes of anti-inflammatory medications (inhaled corticosteroids or cromolyn sodium) to regular bronchodilator medication. The NHLBI awarded contracts for the clinics and coordinating center in September 1991.

The investigators, the sponsor, and the trial’s Data and Safety Monitoring Board (DSMB) approved a protocol for a randomized, controlled clinical trial designed to determine the long-term efficacy and safety of three treatment strategies for mild to moderate asthma in children aged 5 to 12 years at enrollment 29, 30. Budesonide (Pulmicort, Astra USA, Inc.), an inhaled glucocorticoid, and nedocromil (Tilade, Rhone-Poulenc Rorer), an inhaled nonsteroid anti-inflammatory medication, are each being compared with placebo. Every patient uses albuterol (Ventolin, Glaxo Inc.), an inhaled short-acting β-agonist bronchodilator, as needed for asthma symptoms and signs or as a precaution prior to exercise. The planned follow-up period of 5 to 6 years allows most participants to initiate or complete their pubertal growth spurts, thus permitting assessment of the effects of treatments on growth and development. Randomization of patients began in December 1993 and concluded in September 1995; follow-up continues currently. This report describes the design of the trial, the rationale for the design choices, and the methods of the trial.