Childhood Asthma Research and Education (CARE) Network Trial - Montelukast or Azithromycin for Reduction of Inhaled Corticosteroids in Childhood Asthma (MARS)

NCT00471809 | Terminated Phase 4 DMC

• 7 other identifiers: 4475U10HL0643135U10HL0642885U10HL0643055U10HL0642955U10HL0642875U10HL064307
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 6

Brief Summary

The MARS trial is a randomized, double-blind, parallel group study that compares the capacity of azithromycin or montelukast to placebo as effective adjunctive therapy that allows reduction of inhaled corticosteroids in children ages 6 to 17 years with moderate to severe persistent asthma. The primary null hypothesis is that in children with moderate-to-severe persistent asthma, a macrolide antibiotic (azithromycin) or a leukotriene receptor antagonist (montelukast) will provide a steroid-sparing effect when compared to placebo as the dose of inhaled corticosteroid is reduced. This will be tested following achievement of control of symptoms with moderate to high-dose inhaled corticosteroid in combination with a long-acting bronchodilator agonist. Use of these doses for the inhaled corticosteroid will be based on NHLBI step-up guidelines to achieve asthma control.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Time to inadequate asthma control

  Measured at Visit 7

Secondary Outcomes (8)

• Forced expiratory volume in one second (FEV1)

  Measured at Visit 7

• Mean peak flow variability

  Measured at Visit 7

• Asthma symptom scores

  Measured at Visit 7

• Overall asthma control

  Measured at Visit 7

• Quality of life

  Measured at Visit 7

Interventions

Budesonide + Salmeterol + Azithromycin DRUG

Budesonide + Salmeterol + Montelukast DRUG

Budesonide + Salmeterol + Placebo DRUG

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• At Enrollment (V0):
• Age 6-17 years at time of enrollment. A goal of 33% minority and 40% female subjects will be incorporated in recruitment
• Weighs at least 25 kg
• Asthma diagnosed by a physician and present for at least one year prior to study entry
• Moderate to severe persistent asthma:
• Patients will be identified in the following general categories. The general principle is that patients will be uncontrolled on a relatively low dose of ICS that can be stepped-up, or controlled on a moderate or high dose of ICS that can be stepped-down.
• i) On low dose ICS with or without salmeterol and uncontrolled. This patient will be treated with budesonide and salmeterol to determine eligibility criteria. If the addition of salmeterol results in control of symptoms, the patient would be excluded from MARS. If control was not established on low dose budesonide and salmeterol, the dose of budesonide would be increased and entry criteria evaluated based on the algorithm in Figure 1.
• ii) On a dose of ICS equivalent to budesonide at 400 mcg per day with or without any other medication and uncontrolled. This patient will be treated with budesonide and salmeterol to determine eligibility criteria.
• iii) On a dose of ICS equivalent to budesonide at 800 mcg per day with or without any other medication and controlled.
• iv) On a dose of ICS equivalent to budesonide at 1600 mcg per day with or without any other medication and uncontrolled but not requiring prednisone acutely. These patients will be followed to see if they become well controlled with increased adherence or more careful monitoring of symptoms.
• Examples are given for Advair as this drug is a commonly used form of ICS and LABA:
• i) Patients on Advair 100/50 bid and inadequately controlled ii) Patients on Advair 250/50 bid and inadequately controlled iii) Patients on Advair 250/50 bid and well controlled for greater than 3 months and being considered for stepping-down to Advair 100/50 iv) Patients well controlled on Advair 100/50 bid + either montelukast or theophylline for greater than 3 months and being considered for stepping-down to Advair 100/50 bid alone v) Patients on Advair 500/50 bid and well controlled for greater than 3 months and being considered for stepping-down to Advair 250/50 vi) Patients well controlled on Advair 250/50 bid + either montelukast or theophylline for greater than 3 months and being considered for stepping-down to Advair 250/50 bid alone
• Patients on an equivalent of budesonide 400 mcg, 800 mcg, or 1600 mcg per day with no symptoms, but with an FEV1 less than 80% predicted, will be enrolled as uncontrolled and observed closely for symptoms or low peak flows for 2 weeks. The rationale for enrolling these patients and observing them as "uncontrolled" is that patients with an FEV1 below the range of normal may be having symptoms and/or low peak flows that will become apparent under close observation after appropriate education. Note that a percent predicted value for FEV1 will be used only at the enrollment visit, with criteria for control and inadequate control during both run-in and during the double-blind portions of the study using the highest FEV1 value obtained during run-in for decisions prior to randomization and the FEV1 at randomization for decisions subsequent to that visit.
• FEV1 at least 80% predicted if there is going to be step-down at enrollment or at least 50% predicted if already suboptimally controlled historically and to be observed for 2 weeks to define baseline symptoms. FEV1 measurements will be obtained pre-bronchodilator.
• Demonstrate a bronchodilator response with an improvement in FEV1 of at least 12% or airway responsiveness to methacholine with a PC20 less than 12.5 mg/ml.

You may not qualify if:

• At Enrollment (V0):
• More than four courses of systemic corticosteroids for asthma during the 12 months prior to study entry
• More than one hospitalization for wheezing illnesses within the 12 months prior to study entry
• Current treatment with antibiotics for diagnosed sinus disease
• History of severe sinusitis requiring sinus surgery within the past 12 months
• Use of maintenance oral or systemic antibiotics for treatment of an ongoing condition
• Use of macrolide antibiotics within the 6 weeks prior to study entry
• Requirement for prednisone therapy for concurrent illness, e.g., RA, SLE, IBD
• Asthma exacerbation requiring systemic corticosteroids within 4 weeks of study entry
• Contraindication for use of macrolide or LTRA
• Presence of lung disease other than asthma, such as cystic fibrosis and bronchopulmonary dysplasia. Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed
• Presence of other significant medical illnesses (cardiac, liver, gastrointestinal, endocrine, any seizure disorder except febrile seizure in infancy) that would place the study subject at increased risk of participating in the study
• Use of digoxin, ergotamine or dihydroergotamine, triazolam, carbamazepine, cyclosporine, hexobarbital, and phenytoin, and similar classes of medication will be specifically excluded
• Use of omalizumab within one year of study entry
• Gastroesophageal reflux symptoms not controlled by standard medical therapy

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (6)

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Los Angeles, Kaiser Permanente Allergy Department

Los Angeles, California, 90027, United States

Location

Kaiser Permanente Medical Center

San Diego, California, 92111, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792-3244, United States

Location

Related Publications (1)

• Strunk RC, Bacharier LB, Phillips BR, Szefler SJ, Zeiger RS, Chinchilli VM, Martinez FD, Lemanske RF Jr, Taussig LM, Mauger DT, Morgan WJ, Sorkness CA, Paul IM, Guilbert T, Krawiec M, Covar R, Larsen G; CARE Network. Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. J Allergy Clin Immunol. 2008 Dec;122(6):1138-1144.e4. doi: 10.1016/j.jaci.2008.09.028. Epub 2008 Oct 25.

  PMID: 18951618 RESULT

Related Links

• Childhood Asthma Research and Education (CARE) Network

MeSH Terms

Conditions

Asthma

Interventions

Budesonide; Salmeterol Xinafoate; Azithromycin; montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Erythromycin; Macrolides; Polyketides; Lactones

Study Officials

• Vernon M. Chinchilli, PhD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

• Stanley J. Szefler, MD, PhD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Robert F. Lemanske, Jr., MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Robert S. Zeiger, MD, PhD

  Kaiser Permanente Medical Center

  PRINCIPAL INVESTIGATOR

• Robert C. Strunk, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Fernando D. Martinez, MD

  University of Arizona College of Medicine

  PRINCIPAL INVESTIGATOR

• Lynn M. Taussig, MD

  University of Denver

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 8, 2007
• First Posted: May 10, 2007
• Study Start: March 1, 2006
• Study Completion: March 1, 2007
• Last Updated: July 29, 2016

Record last verified: 2012-04

Locations

US (6)