Asthma
Conditions
Brief summary
Primary Objective: * The primary objective is to evaluate the clinical efficacy of telithromycin versus placebo as a supplement to the usual standard of care during an acute exacerbation of asthma. Efficacy will be assessed by: * Changes in the diary card summary symptom score assessed daily for 6 weeks, and * Changes in the domiciliary morning Peak Expiratory Flow Rate (PEFR) following oral telithromycin treatment Secondary Objectives: The secondary objectives of the study are: * To evaluate the microbial activity of telithromycin during an exacerbation of asthma by: * Assessment of the patient's clinical improvement relative to initial C. pneumoniae or M. pneumoniae status, and * Analysis of the quantitative changes from baseline in C. pneumonia or M. pneumoniae by culture and quantitative Polymerase Chain Reaction (PCR). * To evaluate the safety of 10 days of oral telithromycin as a supplement to the standard of care for patients with acute exacerbations of asthma * To assess additional efficacy endpoints and health outcome evaluations following 10 days of treatment with either oral telithromycin or placebo, with either treatment used as a supplement to the standard of care for patients with acute exacerbations of asthma: * Changes and daily variability in the PEFR during the 6 weeks of study treatment, * Health status at follow-up (6 weeks) * Pulmonary function tests: * Forced Expiratory Volume in 1 second (FEV1) * Forced Vital Capacity (FVC) * Forced Expiratory Flow Rate (FEF25-75%) * Need for additional medications (e.g., inhaled corticosteroids, oral corticosteroids, bronchodilator use), * Time to next acute exacerbation of asthma.
Interventions
DRUGTelithromycin
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Patients meeting all of the following criteria will be considered for enrollment in the study: * A documented history of asthma for \>6 months * Presenting within 24 hours of initial medical care in an urgent care clinic, emergency room, or in-patient hospital setting. To qualify for enrollment they must present with the following signs and symptoms of an acute deterioration in asthma control: (reduced PEFR, increased wheeze, and dyspnea, with or without cough). * A PEFR less than 80% of predicted normal * Females who meet the following conditions: * postmenopausal for at least 1 year, or * surgically incapable of bearing children, or * of childbearing potential, and all of the following conditions are met: * had a normal menstrual flow within 1 month before study entry and * has a negative pregnancy test (serum b-subunit human chorionic gonadotropin \[hCG\]) immediately before study entry and * must agree to abstinence or use of an accepted method of contraception
Exclusion criteria
Patients presenting with any of the following will not be included in the study: * Requiring immediate placement in an Intensive Care Unit * Obvious known allergic precipitant for this episode of acute severe asthma (e.g., acute exposure to animal dander) * Pneumonia * Known long QT syndrome or familial history of long QT syndrome (if no previous electrocardiogram \[ECG\] has invalidated this risk factor), or personal history of coronary disease, ventricular arrhythmia, bradycardia \<50 beats/min, or known uncorrected hypokalemia or magnesemia * Known impaired hepatic or renal function * Known diagnosis of myasthenia gravis * Active or quiescent tuberculosis infections of the respiratory tract * Acute exacerbation of chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, or emphysema * A history of smoking of 10 pack-years or more * Women who are breast feeding or are pregnant, as demonstrated by serum or urine pregnancy tests * Suspected or known hypersensitivity to, or suspected serious adverse reaction to the macrolide class of antibiotics * A concomitant condition (including clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease) that would make implementation of the protocol or interpretation of the study results difficult * A recent (within the previous 3 months) history of alcohol or recreational drug misuse. * Immunocompromised patients, including but not limited to: * patients with known human immunodeficiency virus (HIV) infection and have either had or have an AIDS defining condition (e.g., Kaposi's sarcoma, Pneumocystis carinii pneumonia) or a CD4 + T lymphocyte count of \<200/mL * patients with neutropenia (\<1500 neutrophils/mm3) * patients with metastatic or hematological malignancy * splenectomized patients or patients with known hyposplenia or asplenia * Planned surgical treatment at any time during the course of the study that would be incompatible with the objectives of this study * Other disease conditions or infections that could interfere with the evaluation of study treatment efficacy or safety * Oral steroid-dependent asthma * Antibiotic use within 30 days prior to enrollment * Treated within 2 weeks prior to inclusion with CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, and St. John's Wart * Currently receiving medication known to prolong QT interval such as cisapride, pimozide, astemizole and terfenadine, or potent CYP3A4 inhibitors such as antiproteases or ketoconazole. * Patients in whom an antibiotic is clearly indicated. * Have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow-up phase
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patient's daily diary summary symptom scores/Morning diary PEFR | During the Study Conduct |
Secondary
| Measure | Time frame |
|---|---|
| In-clinic pulmonary function tests: Forced expiratory volume in 1 second (FEV1), Percent predicted FEV1, Forced vital capacity (FVC), Forced expiratory flow rate at 25% to 75% of FVC (FEF25-75), PEFR, and percent predicted PEFR | During the study conduct |
| Evening diary PEFR, and diary PEFR variability | During the study conduct |
| Time to symptom resolution from study entry acute exacerbation of asthma | During the study conduct |
Outcome results
None listed