Clinical trial NCT03479736: A Study of Fluoroquinolones Exposure and Collagen-Related Serious Adverse Events
Official title: A Self-Controlled Case Series Study of Fluoroquinolones Exposure and Collagen-related Serious Adverse Events
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Retinal Detachment
Achilles Tendon
Aneurysm, Dissecting
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-03-27
Enrollment: 117911
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All participants with Achilles Tendon Rupture (ATR) or Retinal Detachment (RD) or Aortic Aneurysm and Dissection (AAD), and exposures to Fluoroquinolones (FQ) or any of the other antibiotics or febrile illness not treated with antibiotic, within a defined study period and at least 1 year of continuous enrollment prior to the event.

Brief summary: The purpose of this study is to evaluate whether there is an increased risk of achilles tendon rupture (ATR), retinal detachment (RD) or aortic aneurysm and dissection (AAD) following exposure to fluoroquinolone (FQ) or other antibiotics (amoxicillin, azithromycin, trimethoprim and trimethroprim/sulfamethoxazole) or febrile illness not treated with antibiotics, using a study design that minimizes the impact of confounders not usually captured in health services databases such as heredity or smoking.


Eligibility criteria: Inclusion Criteria:

* Have evidence of at least 1 instance of Achilles Tendon Rupture (ATR) or Retinal Detachment (RD) or Aortic Aneurysm and Dissection (AAD)
* Have at least 1 exposure to Fluoroquinolones or any of the other antibiotics (amoxicillin, azithromycin, trimethoprim and trimethroprim/sulfamethoxazole) or febrile illness not treated with antibiotic
* Have at least 1 year of continuous enrollment with pharmacy benefits prior to the ATR, RD or AAD

Exclusion Criteria:

ATR, AAD and RD cohorts:

- Participants who experience the index event while within a time-at-risk window for more than one exposure type. (The exposure types in this study include FQ as a class, amoxicillin, azithromycin, trimethoprim, trimethroprim/sulfamethoxazole, and febrile illness not treated with antibiotics. Events while within a time-at-risk window of two or more exposure types cannot be associated with any one exposure. Participants are therefore excluded from the study)

For ATR and AAD cohorts:

* Have inherited disorders of connective tissue, specifically: Ehlers-Danlos syndrome, epidermolysis bullosa, Marfan syndrome, osteogenesis imperfecta
* Have an ATR or AAD event prior to index, during the 1-year pre-index period

For RD cohort:

* Have cataract surgery prior to index
* Have iridotomy or iridectomy prior to index

Primary outcomes:
measure: Number of Events Resulting From Collagen-Related Disorders Achilles Tendon Rupture (ATR), Retinal Detachment (RD) and Aortic Aneurysm and Dissection (AAD) by Exposure to Fluoroquinolones (FQ)
timeFrame: Approximately up to 6 years
measure: Number of Events Resulting From Collagen-Related Disorders ATR, RD and AAD by Exposure to Other Antibiotics
timeFrame: Approximately up to 6 years
measure: Number of Events Resulting From Collagen-Related Disorders ATR, RD and AAD by Febrile Illness Not Treated With Antibiotics
timeFrame: Approximately up to 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Titusville
country: United States
facility: Janssen Investigative Site
state: New Jersey
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Londhe AA, Holy CE, Weaver J, Fonseca S, Villasis-Keever A, Fife D. Risk of retinal detachment and exposure to fluoroquinolones, common antibiotics, and febrile illness using a self-controlled case series study design: Retrospective analyses of three large healthcare databases in the US. PLoS One. 2022 Oct 6;17(10):e0275796. doi: 10.1371/journal.pone.0275796. eCollection 2022.
citation: Londhe AA, Holy CE, Weaver J, Fonseca S, Villasis A, Fife D. Risk of aortic aneurysm and dissection following exposure to fluoroquinolones, common antibiotics, and febrile illness using a self-controlled case series study design: Retrospective analyses of three large healthcare databases in the US. PLoS One. 2021 Aug 16;16(8):e0255887. doi: 10.1371/journal.pone.0255887. eCollection 2021.