Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)

NCT00318708 | Completed Phase 3 Results DMC

• 11 other identifiers: 377U10HL0742315U10HL0742317U10HL0742065U10HL0742085U10HL0740735U10HL0742275U10HL0742255U10HL0742045U10HL0742185U10HL074212
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 10

Brief Summary

Asthma can be caused by a variety of factors, including tobacco smoke, allergens, and respiratory airway infections. Many people use inhaled corticosteroid medications to treat their symptoms. These medications, however, are not effective for everyone. Clarithromycin is an antibiotic that may effectively treat asthma in these individuals. This study will evaluate the effectiveness of clarithromycin at controlling asthma symptoms.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Juniper Asthma Control Questionnaire (ACQ) Results

  The Juniper asthma control questionnaire (ACQ) consists of six questions answered by the asthma patient with respect to symptoms, rescue medication use, and night-time awakenings due to asthma. A seventh item in the ACQ is the percent predicted FEV1. Each of the seven items is scored from from 0 (best) to 6 (worst), and then the seven items are averaged to yield a number from 0 (best) to 6 (worst). Asthma patients needed to display an ACQ greater than or equal to 1.25 in order to be eligible for randomization. A reduction of 0.5 units or more in the ACQ over the 16 weeks of treatment is considered to be clinically significant.

  Measured every four weeks during the 16-week treatment period, with the change (week 16 minus baseline) as the primary outcome

Secondary Outcomes (6)

• Asthma Rescue Medication Use

  the week-16 average minus the baseline-week average

• AM Peak Expiratory Flow (PEF)

  the week-16 average minus the baseline-week average

• Forced Expiratory Volume in One Second (FEV1)

  the week-16 value minus the baseline-value

• Methacholine Provocative Concentration (PC20)

  the week-16 value minus the baseline-value

• Exhaled Nitric Oxide (eNO)

  the week-16 value minus the baseline-value

Study Arms (2)

clarithromycin + fluticasone

EXPERIMENTAL

clarithromycin 500 mg twice daily (Biaxin) + fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)

Drug: clarithromycin; Drug: fluticasone propionate

placebo + fluticasone

ACTIVE COMPARATOR

placebo clarithromycin twice daily + fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)

Drug: fluticasone propionate; Drug: placebo clarithromycin

Interventions

clarithromycin DRUG

clarithromycin 500 mg twice daily (Biaxin)

Also known as: Biaxin

clarithromycin + fluticasone

fluticasone propionate DRUG

fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily)

Also known as: Flovent®

clarithromycin + fluticasone; placebo + fluticasone

placebo clarithromycin DRUG

placebo clarithromycin twice daily

Also known as: placebo Biaxin

placebo + fluticasone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• History of physician-diagnosed asthma
• Methacholine PC20 less than or equal to 16 mg/ml and/or FEV1 improvement greater than or equal to 12% in response to 180 mcg albuterol
• Stable asthma for at least 6 weeks prior to study entry
• FEV1 greater than or equal to 60% of predicted result following 180 mcg albuterol
• Juniper ACQ score greater than or equal to 1.5 (optimal ACQ score cut-off point for asthma that is "not well-controlled" by NIH/Global Initiative for Asthma \[GINA\] guidelines)
• Nonsmoker (less than 10 pack-per-year lifetime smoking history and no smoking in the year prior to study entry)
• Able to perform spirometry, as per American Thoracic Society criteria
• % adherence with diary cards, fluticasone (monitored with Doser), and placebo pill trial (monitored electronically with Electronic Drug Exposure Monitor \[eDEM\] pill dose counter) for the final 2 weeks of the four-week run-in period
• At Visit 1, in steroid-naïve participants, no significant adrenal suppression, defined as a plasma cortisol concentration less than 5 mcg/dL. If adrenal suppression occurs, a 250 mcg corticotropin (ACTH) stimulation test will be performed. Plasma cortisol levels will be collected at baseline, and 30 and 60 minutes after the ACTH stimulation test. Participants must have a cortisol concentration greater than 20 mcg/dL on at least one of the post-ACTH time points
• Absence of bronchoscopy-induced exacerbation; if bronchoscopy-induced exacerbation has occurred, prednisone therapy must have stopped at least 6 weeks prior to study entry
• Absence of respiratory tract infection; if infection has occurred, infection-related symptoms must have stopped at least 6 weeks prior to study entry
• Has experienced no more than two exacerbations or respiratory tract infections prior to study entry
• If female and able to conceive, willing to utilize two medically acceptable forms of contraception (one non-barrier method with single barrier method OR double barrier method)

You may not qualify if:

• Presence of lung disease other than asthma
• Presence of vocal cord dysfunction, due to potential confounding of ACQ score
• Significant medical illness other than asthma
• History of atrial or ventricular tachyarrhythmia
• Use of any medication that has a significant interaction with clarithromycin, including herbal or alternative therapies
• Asthma exacerbation within 6 weeks of the screening visit or during the run-in period prior to bronchoscopy
• Use of systemic steroids or change in dose of controller therapy within 6 weeks of the screening visit
• Inability, in the opinion of the study investigator, to coordinate use of dry powder or metered-dose inhaler or to comply with medication regimens
• Inability or unwillingness to perform required study procedures
• Prolonged heart rate corrected QT-interval (greater than 450 msec in women and greater than 430 msec in men) on echocardiogram (ECG) at study entry
• Low potassium or magnesium levels (based on local Asthma Clinical Research Network laboratory definitions)
• Abnormal elevation of liver function tests (AST, ALT, total bilirubin, or alkaline phosphatase)
• Abnormal prothrombin time (PT) or partial thromboplastin time (PTT) results
• Reduced creatinine clearance
• Contraindication to bronchoscopy, as determined by medical history or physical examination

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (10)

University of California, San Diego

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63130, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Wisconsin, Madison

Madison, Wisconsin, 53706, United States

Location

Related Publications (1)

• Sutherland ER, King TS, Icitovic N, Ameredes BT, Bleecker E, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Chinchilli VM, Craig TJ, Denlinger L, DiMango EA, Fahy JV, Israel E, Jarjour N, Kraft M, Lazarus SC, Lemanske RF Jr, Peters SP, Ramsdell J, Sorkness CA, Szefler SJ, Walter MJ, Wasserman SI, Wechsler ME, Chu HW, Martin RJ; National Heart, Lung and Blood Institute's Asthma Clinical Research Network. A trial of clarithromycin for the treatment of suboptimally controlled asthma. J Allergy Clin Immunol. 2010 Oct;126(4):747-53. doi: 10.1016/j.jaci.2010.07.024.

  PMID: 20920764 RESULT

Related Links

• Click here for the Asthma Clinical Research Network (ACRN) web site

MeSH Terms

Conditions

Asthma

Interventions

Clarithromycin; Fluticasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Participants underwent endobronchial biopsy for characterization of lower airway status for M pneumoniae or C pneumoniae. The target sample size was 72 positives and 72 negatives. Only 80 and 12 were recruited, respectively.

Results Point of Contact

• Title: Vernon M. Chinchilli, PhD
• Organization: Penn State Hershey College of Medicine

vchinchi@psu.edu

717-531-4262

Study Officials

• William J. Calhoun, MD

  University of Texas, Galveston

  PRINCIPAL INVESTIGATOR

• Mario Castro, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Robert F. Lemanske, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Richard J. Martin, MD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Elliot Israel, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Stephen P. Peters, MD, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Homer A. Boushey, MD

  University of California, San Francsico

  PRINCIPAL INVESTIGATOR

• Stephen I. Wasserman, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Emily DiMango, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Monica Kraft, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Reuben M Cherniack, MD

  National Jewish Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor and Chair, Department of Public Health Sciences

Study Record Dates

• First Submitted: April 25, 2006
• First Posted: April 27, 2006
• Study Start: June 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: March 23, 2018
• Results First Posted: February 4, 2013

Record last verified: 2018-03

Locations

US (10)