A Pilot Study to Determine the Feasibility and Utility of Implementing of the Full Scale TOM Trial

Study Overview
=================
Brief Summary
-----------------
The primary aim of the pilot (SAPS) protocol is to determine the feasibility and utility of implementing the provisional design of the full scale TOM trial (e.g., the six month treatment period, the impact of the smoking cessation intervention). There is no active hypothesis for the Vanguard Protocol.

Detailed Description
-----------------
The protocol is a small scale pilot of the full-scale TOM trial, and it will utilize a placebo design and incorporates 4 treatment arms. In the Vanguard Protocol all participants are to complete a 4 week run-in with Advair 100/50, followed by randomization to 1 of 4 arms of study treatment. The 4 drug treatment combinations are (2 inhalers, 2 pills): Advair 250/50, Placebo, Placebo, Placebo Advair 100/50 and montelukast, Placebo, Placebo Advair 100/50 and theophylline, Placebo, Placebo Advair 100/50 and ipratropium, Placebo, Placebo The 24 week treatment phase will be followed by a 4 week washout period on Advair 100/50. There is no crossover.

Official Title
-----------------
SAPS:Smoking Asthmatics Pilot Study:

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

Intervention / Treatment
-----------------
* Drug: Fluticasone 250 mg/salmeterol 50 mg
* Drug: Montelukast 10mg
* Drug: Theophylline 400 mg
* Drug: ipratropium


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Gender and Age: Males and females, ages 18- 50 Current Smoker: Smoke at least 5 cigarettes per day for at least 5 years Positive urine cotinine test Asthma: Physician diagnosed asthma Symptomatic, as evidenced by Use of SABA two or more times per week for relief of asthma symptoms, or One or more nocturnal awakenings per week for asthma symptoms ACRC - SC MEETING - 19 MAY 2012 SAPS │ 25 Confidential, not for attribution or citation. Pre-BD FEV1 greater than or equal to 40% predicted Asthma diagnosis confirmed by either albuterol reversibility of FEV1 by 12% or more, or 20% fall in FEV1 at 8mg or less of methacholine If over age 45, a DLco greater than 80% predicted Females of childbearing potential: not pregnant, not lactating and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study. Exclusion Criteria: Diagnosis of COPD or emphysema Other major chronic illnesses in the opinion of the investigator that might interfere with the study: - e.g. including but not limited to uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, renal failure, liver disease, non-skin cancer, unstable psychiatric illness. Recent active substance abuse (in past 6 months) Lung disease other than asthma including COPD, bronchiectasis, sarcoidosis, or other significant lung disease Unstable cardiac disease (decompensated CHF, unstable angina, recent MI, atrial fibrillation, supraventricular or ventricular tachycardia, congenital heart disease, or severe uncontrolled hypertension). High risk of near fatal or fatal asthma as defined by the following 1-3 ICU admission of asthma in the past year more than 2 hospitalizations for asthma in the previous year more than 3 ED visits for asthma in the previous year intubation or ICU admission for asthma in the past 2 years use of more than 2 canisters of inhaled short-acting beta2-agonist in past month Acute asthma exacerbation in the past 4 weeks (treatment with systemic corticosteroids)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 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: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Ipratropium<br>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast. | Drug: ipratropium<br>* Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.<br>* Other names: Atrovent;|
| Placebo Comparator: Theophylline<br>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast. | Drug: Theophylline 400 mg<br>* Participants will be assigned to theophylline once a day for 24 weeks<br>|
| Placebo Comparator: Montelukast<br>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium. | Drug: Montelukast 10mg<br>* Participants will be assigned to montelukast once a day for 24 weeks.<br>* Other names: Singulair;|
| Placebo Comparator: fluticasone 250 mg/salmeterol 50mg<br>Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast. | Drug: Fluticasone 250 mg/salmeterol 50 mg<br>* Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo<br>* Other names: Advair(fluticasone/salmeterol)250/50;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Test | The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score <16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3. | Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and at follow-up visit 1 month off study drug. Median scores over the 24 weeks of treatment were compared. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Asthma Symptom Utility Index (ASUI) | The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation. | Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and a follow-up visit 1 month off study drug. Median scores, change from initial visit and end of treatment, were compared | 
| Percent (%) Perdicted FEV1 Changes | Physiologic measures of % predicted FEV1 | Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks. Median scores over the 24 weeks of treatment were compared | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
asthma,smokers