Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Long-term Observational Study of the Safety of Roflumilast

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03381573
Recruitment Status : Active, not recruiting
First Posted : December 22, 2017
Last Update Posted : April 3, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date December 18, 2017
First Posted Date December 22, 2017
Last Update Posted Date April 3, 2020
Actual Study Start Date March 23, 2017
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 18, 2017)
All-cause mortality [ Time Frame: up to 5 years ]
Safety objective to estimate 5-year all-cause mortality
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: December 18, 2017)
  • death by suicide or hospitalization for suicide attempt [ Time Frame: up to 5 years ]
    Secondary safety issue (occurring up to 5 years)
  • hospitalization for any cause [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • Major cardiovascular events [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • Respiratory disease related hospitalization [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • New diagnoses of depression [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • New diagnoses of malignant neoplasm [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • Hospitalization due to serious diarrhea of non-infectious origin [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • Abnormal and unexplained weight loss [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • New diagnosis of tuberculosis or hepatitis B or C [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
  • Other severe viral hepatitis infection (except hepatitis A) [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Long-term Observational Study of the Safety of Roflumilast
Official Title Long-Term Post-Marketing Observational Study of the Safety of Roflumilast
Brief Summary This is a retrospective cohort study comparing COPD patients aged 40 years and older with new exposure to roflumilast with up to 5 unexposed (ie, not roflumilast-exposed) COPD controls matched by propensity score (PS), age, sex, and year of cohort entry. The study is using electronic healthcare databases in the US (Military Health System database), Germany (GER) (German Pharmacoepidemiological Research Database), and Sweden (SWE) (national databases including healthcare, death, and demographics data). The main objective of this study is to evaluate the long-term safety of roflumilast in the treatment of COPD with main focus on the primary outcome of all-cause mortality and evaluation of potential safety issues identified during the clinical trials of roflumilast. Crude mortality and incidence rates will be compared between roflumilast exposed and unexposed COPD patients and adjusted hazard ratios (HRs) of the primary and secondary outcomes will be calculated
Detailed Description Rationale and background Roflumilast is licensed (i) for maintenance treatment of severe chronic obstructive pulmonary disease (COPD) (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis (CB) in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment (EU) and (ii) as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations (US). As a condition of approval for marketing in the EU, the European Medicines Agency requested the Marketing Authorisation Holder to conduct a long-term comparative observational safety study. Research question and objectives The main objective of this study is to evaluate the long-term safety of roflumilast in the treatment of COPD with main focus on 5-year all-cause mortality and evaluation of potential safety issues identified during the development programme of roflumilast. Study design Retrospective cohort study comparing COPD patients aged 40 years and older with new exposure to roflumilast with up to 5 unexposed (i.e. not roflumilast exposed) COPD controls matched by propensity score (PS), age, sex, and year of cohort entry. PS matching was used as an established method to control for confounding. Crude mortality and incidence rates were compared between roflumilast exposed and unexposed COPD patients and adjusted hazard ratios (HRs) of the primary and secondary outcomes were calculated in GER and SWE, while in the US adjusted HRs were only calculated for the primary outcome and are not yet available for secondary outcomes. Reported adjusted HRs for secondary outcomes therefore only refer to GER and SWE. Setting Electronic healthcare databases in the United States (US), Germany (GER), and Sweden (SWE) holding demographic data, data on health, and dispensing of medication. The initial assessment of the number of cohorts in each database including the years 2011, 2012, and 2013 resulted in a total of 54985 (9573 exposed), 50493 (8775 exposed), and 18602 (3207 exposed) COPD patients in the US, GER, and SWE, respectively. Variables and data sources Exposure variable: Use of roflumilast (ATC code R03DX07) Outcomes: The primary outcome in the study is 5-year all-cause mortality. Secondary outcomes are death by suicide or hospitalisation for suicide attempt, hospitalisation for any cause, major cardiovascular events, respiratory disease related hospitalisation, new diagnosis of depression, new diagnosis of malignant neoplasm, hospitalisation due to serious diarrhoea of non-infectious origin, abnormal and unexplained weight loss, and new diagnosis of tuberculosis or hepatitis B or C or other severe viral hepatitis infection (except hepatitis A). Other covariates: Characterisation of baseline therapy, baseline medical history and other socio-demographic covariates. Data sources: Military Health System database (US), German Pharmacoepidemiological Research Database (GER), national databases including healthcare, death, and demographics data (SWE).
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population unselected COPD patients aged 40 years and older, reflecting the use of roflumilast in a real-life setting.
Condition COPD
Intervention Drug: Roflumilast
Roflumilast
Study Groups/Cohorts
  • Roflumilast exposed
    Patients with COPD ever exposed to Roflumilast
    Intervention: Drug: Roflumilast
  • Roflumilast unexposed
    Patients with COPD never exposed to Roflumilast
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Actual Enrollment
 (submitted: September 2, 2019)
99999
Original Estimated Enrollment
 (submitted: December 18, 2017)
124080
Estimated Study Completion Date December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Exposed Cohort selection

Inclusion Criteria:

  • Have one or more prescription(s) of roflumilast with the date of first prescription/dispensation defined as the Cohort Entry Date
  • Have active data in the respective database(s) for at least 1 year prior to the Cohort Entry Date
  • Be at least 40 years old at Cohort Entry Date
  • Have a diagnosis of COPD or chronic bronchitis prior to the Cohort Entry Date (databases with outpatient diagnoses) or (databases without outpatient diagnoses) either a hospital diagnosis of COPD or chronic bronchitis prior to the Cohort Entry Date or a proxy for such indication based on prescription data.

Non-Exposed Cohort selection Patients meeting the following inclusion criteria belong in the Non-Exposed Cohort and are eligible as Matched Non-Exposed controls. Each patient in the Non-exposed Cohort selected as matched exposed patient is assigned as a Cohort Entry Date the date of the first roflumilast prescription of the matched exposed patient.

Sex/Gender
Sexes Eligible for Study: All
Ages 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Germany,   Norway,   Sweden,   United States
Removed Location Countries Finland
 
Administrative Information
NCT Number NCT03381573
Other Study ID Numbers D7120R00003
EUPAS14852 ( Registry Identifier: ENCePP )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party AstraZeneca
Study Sponsor AstraZeneca
Collaborators Not Provided
Investigators
Principal Investigator: Edeltraut Garbe, Dr. med. Leibniz Inst for Prevention & Epidemiology - BIPS GmbH
PRS Account AstraZeneca
Verification Date April 2020