Multinational, multi-database cohort study to assess adverse cardiovascular and cerebrovascular outcomes and mortality in association with inhaled NVA237 in Europe (NVA237 PASS)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (R03BB06) glycopyrronium bromide

  glycopyrronium bromide
• Medical condition to be studied:
  Chronic obstructive pulmonary disease

Population studied

• Short description of the study population:
  Population of patients, 40 years of age or older with at least 1 year of valid database history and a recorded diagnosis of COPD.; Inclusion criteria; All patients aged 40 years or older who were diagnosed with COPD and had at least one year of database history and a first time prescription/dispensing for one of the following medications after 01 November 2012 were included in the study: NVA237 or a single ingredient LAMA (other than NVA237) or a single-ingredient LABA.; Exclusion criteria; Patients with 1) missing data on age or gender, 2) a recorded diagnosis of asthma only and thus, no recorded diagnosis of COPD prior to or within six months after the first prescription/dispensing of any of the drugs of interest, or 3) who received the study drug of interest (NVA237, LAMA [excluding NVA237] or LABA) in the one year prior to the index date (= time of first prescription) of the respective study cohorts were excluded. Patients thus needed to be treatment-naïve to the exposure of interest for a minimum of one year. In addition, patients treated with both LABA and LAMA at the time of first prescription/dispensing of the study drug of interest were excluded from the study. As this was a non-interventional study using real-world data, it was decided to not exclude patients with non-cardiovascular life-threatening conditions (i.e., defined as patients with underlying cancer.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Chronic obstructive pulmonary disease (COPD) patients
• Estimated number of subjects:
  3000

Study design details

• Main study objective:
  To assess the incidence rates and hazard ratio of cardiovascular and cerebrovascular outcomes, and of mortality among new users of inhaled NVA237 with COPD compared to new users of LAMA (non-NVA237) or new users of LABA in patients with COPD.
• Outcomes:
  • Major cardiovascular events •Ischemic heart disease including myocardial infarction and angina pectoris•Cardiac arrhythmias •Atrial fibrillation/flutter •Cerebrovascular disorders •Mortality
• Data analysis plan:
  As primary analysis, the risk of overall mortality as well as the risk of the different endpoints of interest among new users of NVA237 will be compared to the risk in the new users of LABA and other LAMA using Cox regression analysis. Cox regression analyses will be conducted to estimate both crude and adjusted relative risks (expressed as hazard ratios HRs with 95% confidence intervals 95% CIs), allowing for time-varying exposures. All analyses will at first be performed for each database separately. Effect estimates will be pooled across the databases, using a random effects meta-analytical approach. In addition, a pooled mega-analysis will be done by combining the data sources on a patient-level and adjusting for the database.As secondary analysis, subsequent episodes, with or without treatment, will be taken into account. For this analysis, the HR of the events of interest will be estimated for NVA237 vs. no use of NVA237.

Documents

Study results

NVA237A2402T-Redacted-Final-Study-Report