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

Janssen (J&J Innovative Medicine)

Status: Completed

Conditions: Achilles Tendon; Retinal Detachment; Aneurysm, Dissecting

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

Study type: Observational

Funder types: Industry

Identifiers

NCT03479736

CR108453

RRA-19796 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 117,911 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

117,911 participants in 3 patient groups

Cohort 1: Participants with Achilles Tendon Rupture (ATR)

Description:

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).

Treatment:

Other: Febrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

Drug: Other Antibiotics

Drug: Oral Fluoroquinolones (FQ)

Cohort 2: Participants with Retinal Detachment (RD)

Description:

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).

Treatment:

Other: Febrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

Drug: Other Antibiotics

Drug: Oral Fluoroquinolones (FQ)

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

Description:

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).

Treatment:

Other: Febrile Illness Not Treated with Antibiotics Will be Analyzed as an Exposure

Drug: Other Antibiotics

Drug: Oral Fluoroquinolones (FQ)