A phase IIIb multicenter, 52 week treatment, randomized, blinded, double dummy, parallel group efficacy study comparing the effect of inhaled indacaterol 150 µg o.d. vs inhaled tiotropium 18 µg o.d. on lung function, rate of exacerbations and related outcomes in patients with COPD - INVIGORATE
- Conditions
- -J449 Chronic obstructive pulmonary disease, unspecifiedChronic obstructive pulmonary disease, unspecifiedJ449
- Registration Number
- PER-058-09
- Lead Sponsor
- OVARTIS BIOSCIENSES PERU S.A.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 86
• Adult men and women aged 40 years or older, who have signed an Informed Consent form before the start of any procedure related to the study
• Co-operative outpatients with a diagnosis of severe COPD (severe according to the classification by the GOLD Guidelines, 2007) and including; a) Smoking history of at least 10 packs per year b) Post-bronchodilator FEV1> 50% and> 30% of the predicted normal value c) Post-bronchodilator FEV1 / CVF <70% d) A documented history of at least 1 moderate or severe exacerbation in the previous 12 months. See Section 7.4.2 for the definition of an exacerbation of COPD.
• Pregnant or breastfeeding women (breastfeeding), where pregnancy is defined as the status of a woman after conception and until the end of pregnancy, confirmed by a laboratory test of positive human chorionic gonadotropin in the serum (> 5 mlU / mL).
• Women with reproductive potential, defined as all women physiologically capable of becoming pregnant, including those whose career, lifestyle or sexual orientation impede sexual relations with a male partner and women whose partner has been sterilized by a vasectomy or By other means,
• Patients with a body mass index (BMI) less than 15 or greater than 40 kg / m2
• Patients requiring oxygen therapy for chronic hypoxemia (excluding acute exacerbation of COPD). These are patients that typically require oxygen therapy> 15 h per day administered by an oxygen cylinder or concentrator at home.
• Patients who have had a respiratory tract infection within 6 weeks prior to Visit 2. Patients who develop a respiratory tract infection between Visit 2 and Visit 4 should be discontinued from the study, but they may be re-admitted. Recruit later once the inclusion / exclusion criteria have been met.
• Patients who have had an exacerbation of COPD that has required systemic treatment with glucocorticoids and / or antibiotics in the 6 weeks prior to selection (Visit 2). In the event that the exacerbation occurs during the period of admission, the patient should discontinue the study. The patient can be re-recruited once the inclusion / exclusion criteria have been met.
• Patients with concomitant lung disease, pulmonary tuberculosis (unless confirmed by chest radiography that is no longer active) or clinically significant bronchiectasis.
• Patients with a history (in Visit 1) of asthma
• Patients with Type I diabetes or uncontrolled Type II diabetes including patients with a history of blood glucose levels consistently outside the normal range or of an HbAlc> 8.0% of the total Hb measured in the selection (Visit 2).
• Patients with contraindications to treatment with tiotropium including a medical history of symptomatic prosthetic hypertrophy, obstruction of the bladder neck, narrow angle glaucoma and moderate to severe renal impairment and / or hypersensitivity to other anticholinergics.
• Patients who, in the opinion of the investigator or responsible Novartis staff, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding stable chronic atrial fibrillation) or other clinically significant findings of the ECG, uncontrolled hypertension and other significant heart disease or conduction defects, hypocontrol and uncontrolled hyperthyroidism, hypokalemia, hypertrenergic condition or any condition that in the opinion of the investigator or responsible Novartis staff could compromise the safety or patient compliance, interfere with the evaluation or prevent the completion of the study.
• Patients with lung cancer or with a history of lung cancer.
• Patients with an active malignancy or history of malignancy of any organ system (other than a localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, whether or not there is evidence of local recurrence or metastasis. Patients with a history of malignancy and 5 years or more of disease-free survival time can be included in the study only in accordance with Novart
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:The primary objective of the study was to demonstrate the non-inferiority of indacaterol vs. tiotropium with respect to 24 hour post dose (trough) FEV1 after 12 weeks of treatment in patients with severe COPD. Trough FEV1 was defined as the average of the 23 hours 10 min and the 23 hours 45 min post dose values. Trough FEV1 was analyzed using a mixed model for the PPS-S. The model contained treatment as a fixed effect with the baseline FEV1, FEV1 prior to inhalation and FEV1 15 min post-inhalation of salbutamol/albuterol (components of SABA reversibility at Visit 2), FEV1 prior to inhalation and FEV1 60 min post-inhalation of ipratropium (components of anti-cholinergic reversibility at Visit 3) as covariates. Smoking history (current or ex-smoker) was included as a factor in the model.<br><br>Measure:Trough Forced Expiratory Volume in 1 Second (FEV1).<br>Timepoints:12 weeks<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:COPD exacerbations were defined as :Worsening of 2 or more major symptoms for at least 2 consecutive days: dyspnea; sputum volume; suputum purulence AND requiring treatment with systemic corticosteroids and/or antibiotics OR Worsening of any 1 major symptom together with any 1 of the following minor symptoms for at least 2 consecutive days: Sore throat; colds; fever without other cause; increased cough; increase wheeze AND requiring treatment with systemic glucocorticosteroids and/or antibiotics. The rate was analyzed using a linear model assuming a negative binomial distribution for the PPS-E. The time at risk for a patient was defined as the length of time the patient was in the study and the log(length of time in the study) was used as the offset variable in the model.<br><br>Measure:Rate of COPD Exacerbations<br>Timepoints:52 weeks<br>