Efficacy and Safety of Indacaterol vs Tiotropium in Women With COPD Secondary to Biomass Exposure

Study Overview
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Brief Summary
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Chronic Obstructive Pulmonary Disease (COPD) is a disease that produces a high rate of social and economic health mortality and morbidity not only in our country but in the international field. The causes of this disease are well-known, being smoking what produces the major portion and the less (but no less important) frequently, biomass exposure (when people cook or warm the house). It is described that the COPD secondary to biomass exposure it is approximately a third half of all the cases in cohorts in patients with this disease. Patients clinical affection with COPD by biomass is different from the one described in patients by smoking, being the most frequent the affection peripheral airway, with major proportion of symptoms such as dyspnoea, cough and expectoration (Phenotype chronic bronchitis), major frequency of exacerbations, as well as, major affection in the quality of life related to health and a minimum emphysema proportion. Currently, there is a trend of paying attention on the outcomes based on patients, such as symptoms, quality of life and the risk prevention (exacerbations) as it is exposed in the strategy GOLD 2011. In that way, the bronchodilators use as a pillar in the COPD due to the utility for the exacerbation prevention, symptomatic improvement and in quality of life, predominating the utility of ultra long-acting bronchodilators, such as tiotropium. Recently, it is available more information on new bronchodilators as indacaterol, demonstrating at least no inferiority effect on FEV1, inspiring capacity (in fact, discreet superiority on the last one) and symptoms. A functional outcome clinically important is the capacity of exercising; Six-Minute Walk Test (6MWT) has been widely used to predict prognosis of COPD secondary to smoking. This test has not been evaluated in predicting the response to the specific treatment in patients with COPD secondary to biomass exposure. Long-acting bronchodilators have been demonstrated a benefit to the patients with COPD by smoking, in the exercising capacity measured by 6MWT. There are several reasons why this outcome could be more relevant especially in this population: inhabit in rural areas where people walk long distances, most of them are women and they are usually in charge of all the housework. Almost all the studies reported until now exclude patients with COPD due to some cause other than smoking. Due to the lack of information on this item and the particularities in this clinical and functional characteristics observed in this kind of patients, it is considered that these patients will be benefit with the use of ultra long-acting bronchodilators, to long period and, potentially can be observed additional benefits in the decrease of the frequency of the exacerbations and symptomatology as well as other important outcomes such as the functional, respiratory capacity among others.

Detailed Description
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The use of bronchodilators is an invaluable tool in COPD, in outcomes such as the exacerbation preventions, improvement of symptoms and exercise capacity and therefore in quality of life. However, as the efficacy as the security such as bronchodilators benefits that have only been characterized in patients with COPD secondary to smoking and it is only assumed benefits in COPD by other causes but without confirmation. There are no national or international studies that describe the ultra long-acting bronchodilator's efficacy and security in COPD secondary to biomass exposure (BE). The proportion of patients with COPD secondary by biomass exposure vary between 20-30%, depending on what kind of study and population, which is an important number leading to a great mortality, morbidity, social and economic, being important to characterize in a better way several relevant aspects such as the long period treatment response. The proportion of patients with COPD by BE presents major proportion of phenotype bronchitis with major condition of peripheral airways level, with major proportion of dyspnoea and a decrease in the quality of life. It is precisely in these aspects where have been demonstrated benefits with ultra long-acting bronchodilators, as consequence, it is expected that this group of patients will be benefitted equal and perhaps in greater magnitude that those that are encompassed in the emphysematous phenotype. Additionally, it is well described that the sub-diagnostic and sub-optimum treatment in patients with COPD in first level; because this kind of patients generally have low social-economic status and assuming that in the first level they will find the principal attention, it would be important to define major therapeutic alternatives in them. As it was mentioned before, the exercising capacity is a functional outcome deeply studied with prognostic capacity in patients with COPD secondary to smoking; it is probably that it could be an outcome with major impact in this special group of patients (COPD secondary to biomass exposure), because they live, in general, in rural areas, heads of household and therefore, in terms of social rolls their functionality requirement is higher. Finally, there is a finding well described the low adherence to patient's treatment with COPD, with various reasons including low economic resources and others such as devices of complicated application, multiple dosage, etc. Due to the fact that most of the people who suffer COPD by biomass exposure are women dedicated to housework all the day, it is probable that this kind of medicines (dosage once a day) as well as free treatment, is a strategy that improves the treatment adherence and could represent an improvement in the important outcomes in this devastating disease (functional capacity, quality of life, frequency of exacerbations, mortality).

Official Title
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Efficacy and Safety of Indacaterol vs tiotropiuM on walkEd Distance From Baseline to 24 Weeks, in Women With modeRAte-severe COPD Secondary to Biomass Exposure: Randomized, Non Inferior, Open Label, Parallel Groups Clinical Trial

Conditions
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COPD

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: >50 Female (female eligibility criteria are: Women in no fertile age who are non pregnant and committed to use effective contraception).*See note. Relation FEV1/FVC less than 70% of predicted and the index obtained by the relation between the hours and the years of exposure (IEHL) more than 100 hrs/year (COPD of any grade or symptomatic). Be able to assist at all the study visits. Informed consent signed. Be able to perform the functional pulmonary test satisfactorily. Without any contraindication to perform any functional pulmonary test or exercise ( six-minute walking test. Stable COPD (No history of exacerbations in the last 6 weeks previous to the inclusion). In treatment with inhaled steroid at least 4 weeks before the inclusion. Smoking index less than 5. If the subject is chronic - degenerative diseases associated, these must be controlled. II-III functional class that allow her assist to the study visits. *Note: This problem predominates in WOMEN, as gender and roles (predominately in rural areas) who are the ones that cook and are exposed enough time to appear the comorbidity associated (COPD, headache, backache, conjunctival irritation, etc). That is why in this study were included only women because this is a problem of gender and poverty. Women with at least 5 years with amenorrhea (postmenopause). Exclusion Criteria: History of: Allergy or known intolerance to any of the bronchodilator drugs in the study. Asthma, bronchiectasis (as tuberculosis, whooping cough or other infection sequelae associated in the clinic history), tuberculosis, COPD recent exacerbation or acute respiratory infection. Cardiovascular disease recent (less than 3 months) that contraindicate the functional pulmonary test. Patients of childbearing age who do not agree to use effective methods of contraception. Patients with suspected cancer at any level.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol<br>Indacaterol 150 mcgr, one inhaled capsule, dose once daily, with dry powder inhaler device. | Drug: Indacaterol<br>* Indacaterol, one inhales capsule, 150 mcgr, by dry powder dispositive<br>* Other names: Onbrize;|
| Active Comparator: Tiotropium<br>Tiotropium 18 mcgr, 1 inhaled capsule, dose once daily, with dry powder inhaler device | Drug: Tiotropium<br>* Tiotropium 18 mcgr, one inhaled capsule, by dry powder inhaler handihaler<br>* Other names: Spiriva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on the pulmonary function in functional capacity (walked meters on six minute walking test, 6MWT) from baseline to 6 month treatment. | Changes on the pulmonary function in functional capacity | Baseline, 1, 3 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in exacerbations (rate exacerbations/patient/year). Total frequency of exacerbations, frequency of exacerbations that required hospitalization and exacerbations free period since the baseline up to 1, 3 and 6 month treatment. | The exacerbation outcome will be measured according to the use of health resources and through the confirmation with the symptoms diary. | Baseline, 1, 3 and 6 months | 
| Changes in pulmonary function (forced respiratory volume in first second (FEV1), forced vital capacity (FVC) and inspiratory capacity (IC)) | Changes in exacerbations | Baseline, 1, 3 and 6 months | 
| Changes in quality of life (COPD Assessment Test (CAT) and Saint George Respiratory Questionnaire (SGRQ)) | Changes in quality of life | Baseline, 1, 3 and 6 months | 
| Changes in dyspnea (modified Medical Research Council (mMRC) scale, Transition Dyspnea Index (TDI) questionnaires). | Changes in dyspnea | Baseline, 1, 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Biomass