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CompletedNCT03479736Updated Jun 25, 2025

A Study of Fluoroquinolones Exposure and Collagen-Related Serious Adverse Events

An observational study in Retinal Detachment, Achilles Tendon and Aneurysm, Dissecting, sponsored by Janssen Research & Development, LLC. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2025-06-25.

Sponsored by Janssen Research & Development, LLC · Observational

Study type
Observational
Model
Other
Time perspective
Retrospective
Enrollment
117,911
Sex
All
01

Study 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.

02

Conditions studied

  • Retinal Detachment
  • Achilles Tendon
  • Aneurysm, Dissecting
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No
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.

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

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
04

Study design

Observational model
Other
Time perspective
Retrospective
Enrollment
117,911 participants (actual)
Patient registry
No

Groups and cohorts

  • Cohort 1: Participants with Achilles Tendon Rupture (ATR)

    Participants will be defined as having ATR if they receive a diagnosis for ATR as well as one of the following procedures: tenotomy or primary ruptured Achilles Tendon (AT) repair (with or without graft) within 7 days of diagnosis. Index will be based on the earlier date of diagnosis or procedure. Participants with ATR, and exposures to Fluoroquinolone (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 will be included. It will use data from 3 databases, which are Truven CCAE and Medicare (Supplemental) and Optum ClinFormatics (Optum).

    Drug: Oral Fluoroquinolones (FQ) · Drug: Other Antibiotics · Other: Febrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

  • Cohort 2: Participants with Retinal Detachment (RD)

    Participants will be defined as having a RD if they received a diagnosis of RD and a procedure for RD, e.g.: sclera buckle, vitrectomy, retinopexy, retinal cryotherapy, silicone oil fill, air gas fluid exchange or pneumatic retinopexy, within 14 days of index. Index will be defined as the earlier date of diagnosis or procedure. Participants with RD, and exposures to 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 will be included. It will use data from 3 databases, which are Truven CCAE and Medicare (Supplemental) and Optum ClinFormatics (Optum).

    Drug: Oral Fluoroquinolones (FQ) · Drug: Other Antibiotics · Other: Febrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

  • Cohort 3: Participants with Aortic Aneurysm & Dissection (AAD)

    Participants will be defined as having AAD if they received a primary diagnosis for aortic aneurysm, aortic rupture or dissection and have also received an aortic repair surgical procedure concurrently to the AAD diagnosis, in an inpatient or emergency department (ED) setting. Index will be defined as the earlier date of diagnosis or procedure. Participants with AAD, and exposures to 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 will be included. It will use data from 3 databases, which are Truven CCAE and Medicare (Supplemental) and Optum ClinFormatics (Optum).

    Drug: Oral Fluoroquinolones (FQ) · Drug: Other Antibiotics · Other: Febrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

Interventions

  • DrugOral Fluoroquinolones (FQ)

    Participants will not receive any intervention as a part of this study. The FQ include all oral forms of FQ (24-hours extended release tablets, extended release tablets, oral solution, oral suspension, oral tablet, pack). The drugs included are ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin.

  • DrugOther Antibiotics

    Participants will not receive any intervention as a part of this study. Other antibiotics include amoxicillin, azithromycin, trimethoprim and trimethroprim/sulfamethoxazole.

  • OtherFebrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

    Febrile illness not treated with antibiotics is defined as: concurrent diagnoses of viral disease with concurrent fever, and no concurrent prescription for any antibiotic during the 60-day period before and after the first date of viral disease diagnosis; or a diagnosis of influenza with no concurrent inpatient admission during the 60-day period pre- or post-influenza diagnosis, and no prescription for any antibiotics during the 60-day period pre- or post-influenza diagnosis.

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What researchers measure

Primary outcomes

  1. 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)

    Participants will be having ATR if they receive a diagnosis for ATR and 1 of the following: tenotomy/primary ruptured AT repair (with/without graft) within 7 days of diagnosis. Participants will be having RD if they receive a diagnosis of RD and a procedure for RD, e.g.: sclera buckle, vitrectomy, retinopexy, retinal cryotherapy, silicone oil fill, air gas fluid exchange or pneumatic retinopexy, within 14 days of index (earlier date of diagnosis/procedure). Participants will be having AAD if they receive a diagnosis for aortic aneurysm, aortic rupture/dissection and an aortic repair surgical procedure concurrently to it, in an inpatient/ED setting. The FQ include all oral forms of FQ (ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin). Relative risk of RD, ATR, and AAD between periods of exposure and non-exposure to FQ will be assessed using number of events. Temporal associations between RD, ATR or AAD and exposure to FQ will be estimated.

    Time frame: Approximately up to 6 years

  2. Number of Events Resulting From Collagen-Related Disorders ATR, RD and AAD by Exposure to Other Antibiotics

    Other antibiotics includes amoxicillin, azithromycin, trimethoprim and trimethroprim/sulfamethoxazole. Relative risk of RD, ATR, and AAD between periods of exposure and non-exposure to other antibiotics will be assessed using number of events. Temporal associations between RD, ATR or AAD and exposure to other antibiotics will be estimated.

    Time frame: Approximately up to 6 years

  3. Number of Events Resulting From Collagen-Related Disorders ATR, RD and AAD by Febrile Illness Not Treated With Antibiotics

    Febrile illness not treated with antibiotics is defined as: concurrent diagnoses of viral disease with concurrent fever, and no concurrent prescription for any antibiotic during the 60-day period before and after the first date of viral disease diagnosis; or a diagnosis of influenza with no concurrent inpatient admission during the 60-day period pre- or post-influenza diagnosis, and no prescription for any antibiotics during the 60-day period pre- or post-influenza diagnosis. Relative risk of RD, ATR, and AAD between periods of exposure and non-exposure to febrile illness not treated with antibiotics will be assessed using number of events. Temporal associations between RD, ATR or AAD and febrile illness not treated with antibiotics (analyzed as an exposure) will be estimated.

    Time frame: Approximately up to 6 years

06

Study locations

1 site
  • Janssen Investigative Site
    Titusville, New Jersey 08560, United States
07

References and documents

Publications

  • 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. PubMed 36201545 ↗
  • 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. PubMed 34398907 ↗
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Registry details

Key details

Study ID
NCT03479736
Lead sponsor
Janssen Research & Development, LLC
Responsible party
Sponsor
First posted
Mar 27, 2018
Start date
Nov 20, 2017
Primary completion
May 21, 2018
Completion
Jun 4, 2018
Last update
Jun 25, 2025

Study contacts

Janssen Research & Development, LLC Clinical Trial
study director · Janssen Research & Development, LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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