telicast : telithromycin in acute exacerbations of asthma

Conditions: Asthma

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.


Eligibility criteria:
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