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Long-term Observational Study of the Safety of Roflumilast

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ClinicalTrials.gov Identifier: NCT03381573
Recruitment Status : Recruiting
First Posted : December 22, 2017
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment
COPD Drug: Roflumilast

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
Estimated Enrollment : 124080 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Long-Term Post-Marketing Observational Study of the Safety of Roflumilast
Actual Study Start Date : March 23, 2017
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Roflumilast

Group/Cohort Intervention/treatment
Roflumilast exposed
Patients with COPD ever exposed to Roflumilast
Drug: Roflumilast
Roflumilast

Roflumilast unexposed
Patients with COPD never exposed to Roflumilast



Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: up to 5 years ]
    Safety objective to estimate 5-year all-cause mortality


Secondary Outcome Measures :
  1. death by suicide or hospitalization for suicide attempt [ Time Frame: up to 5 years ]
    Secondary safety issue (occurring up to 5 years)

  2. hospitalization for any cause [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  3. Major cardiovascular events [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  4. Respiratory disease related hospitalization [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  5. New diagnoses of depression [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  6. New diagnoses of malignant neoplasm [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  7. Hospitalization due to serious diarrhea of non-infectious origin [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  8. Abnormal and unexplained weight loss [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  9. New diagnosis of tuberculosis or hepatitis B or C [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)

  10. Other severe viral hepatitis infection (except hepatitis A) [ Time Frame: up to 5 years ]
    secondary safety issue (occurring up to 5 years)



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03381573


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
United States, Massachusetts
Quintiles, Inc Recruiting
Cambridge, Massachusetts, United States, 02139
Finland
Epid Research Recruiting
Espoo, Finland
Germany
Leibniz-Institut Für Epidemiologie Und Präventionsforschung-Bips Gmbh Recruiting
Bremen, Germany
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Edeltraut Garbe, Dr. med. Leibniz Inst for Prevention & Epidemiology - BIPS GmbH

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03381573     History of Changes
Other Study ID Numbers: D7120R00003
EUPAS14852 ( Registry Identifier: ENCePP )
First Posted: December 22, 2017    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019