Clinical trial NCT01381406: Impact of Initiating Tiotropium Alone Versus Initiating Tiotropium in Combination With Fluticasone Propionate/Salmeterol Xinafoate Combination (FSC) on Chronic Obstructive Pulmonary Disease-related Outcomes in Patients With Pre-existing Exacerbations
Official title: Impact of Initiating Tiotropium Alone Versus Initiating Tiotropium in Combination With Fluticasone Propionate/Salmeterol Xinafoate Combination (FSC) on Chronic Obstructive Pulmonary Disease-related Outcomes in Patients With Pre-existing Exacerbations
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 3333
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Data for managed-care enrollees age 40 and older with a diagnosis of COPD and an index event of at least one pharmacy claim for TIO during the study period (January 1, 2003 through April 30, 2008) were identified. Subjects were required to have ≥1 exacerbation in the pre-index period (defined as a COPD-related emergency room visit or hospitalization), ≥1 prescription claim for ipratropium or ipratropium/albuterol combination in the pre-index period, ≥2 prescriptions for TIO (including the index prescription) during the post-index period, no prescription for FSC during the pre-index period, and no exacerbation or hospital/emergency room visit within 30 days after the index date. ICD-9-CM code 490.xx, bronchitis not specified as chronic or acute, was included in an attempt to enhance the validity of the analysis by capturing patients with chronic bronchitis whose condition was coded incorrectly.

Brief summary: This was a retrospective cohort design using administrative claims data from Jan 1, 2003 through Sep 30, 2007, representing the years of available data, were used for this study. Managed care enrollees having at least one pharmacy claim for tiotropium (TIO) during the study period were identified as the target population. An index TIO prescription was defined as the first chronologically occurring pharmacy claim for TIO during the period Jan 1, 2004 to Aug 31, 2006, called the enrollment period. The date of the index TIO prescription was termed as the index Rx date, and the 1-year period before the index Rx date was termed as the pre-index period. The period after the index date was termed as the post-index date, and is further divided into a 30-day combination assessment period and a 1-year follow-up period. COPD clinical and economic outcomes were measured in a variable length follow up period.

The combination assessment period, defined as the 30-day period following the index Rx date, was used to categorize patients into 2 cohorts: TIO alone or TIO + FSC (fluticasone propionate/salmeterol xinofoate combination) depending on whether they use FSC in combination with TIO during this period. Combination therapy with TIO + FSC was defined as having an FSC claim on the same date as the TIO claim or a TIO and FSC pharmacy claim with overlapping days supply occurring within 30 days of index Rx date. Enrollees adding FSC for the first time after the 30-day combination assessment period were excluded from the sample, thus ensuring that the TIO-alone cohort is not using FSC. No outcomes were assessed in the 30-day combination assessment period. The 1-year period after the end of the 30-day combination assessment period was termed as the follow-up period and was used to assess all study outcomes. Enrollees were required to be continuously eligible in their health plans during the pre-index and post-index periods for a total of 25 months. An intent-to-treat approach was used for the analyses. Thus, patients identified to be in a drug therapy cohort were considered to be using that therapy during the entire follow-up period, regardless of therapy discontinuations.

Specifically the study hypothesis for the primary outcome being tested was:

Ho: There is no difference in risk of any COPD-related exacerbation between TIO+FSC and TIO cohorts Ha: There is a difference in risk of any COPD-related exacerbation between TIO+FSC and TIO cohorts

Hypothesis for the key secondary outcome of COPD-related costs that was tested was:

Ho: There is no difference in COPD-related costs between TIO+FSC and TIO cohorts Ha: There is a difference in COPD-related costs between TIO+FSC and TIO cohorts


Eligibility criteria: Inclusion Criteria:

* Continuous health plan eligibility in the pre- and post-index periods
* age ≥40 years at the index date
* Presence of at least 1 claim with an ICD-9-CM code for COPD in any diagnosis field (490.xx, 491.xx, 492.xx, 496.xx) in the pre- and post-index period
* ≥1 exacerbation in the pre-index period (defined as a COPD-related Emergency Room visit or hospitalization)
* ≥1 prescription claim for ipratropium or ipratropium/albuterol combination in the pre-index period
* an index event of at least one pharmacy claim for TIO (tiotropium) combination in the pre-index period during the study period (January 1, 2003 through April 30, 2008)
* ≥2 prescriptions for TIO (including the index prescription) during the post-index period

Exclusion Criteria:

* presence of comorbid conditions (respiratory cancer, cystic fibrosis, fibrosis due to tuberculosis \[TB\], and bronchiectasis, pneumonociosis, pulmonary fibrosis, pulmonary TB, sarcoidosis) during the pre- and post-index periods
* use of FSC in pre-index period
* exacerbation (emergency room visit or hospitalization) within 30 days after the index date

Primary outcomes:
measure: Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: Data were collected over a maximum period of 4 years
Secondary outcomes:
measure: Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group
timeFrame: Data were collected over a maximum period of 4 years
measure: Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years
timeFrame: Data were collected over a maximum period of 4 years
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: