TELICAST : Telithromycin in Acute Exacerbations of Asthma

Study Overview
=================
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.

Official Title
-----------------
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Telithromycin 800 mg (Once Daily for 10 Days) as a Supplement to the Standard of Care for Patients With Acute Exacerbations of Asthma

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Telithromycin


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Telithromycin|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's daily diary summary symptom scores/Morning diary PEFR |  | During the Study Conduct | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |