Infectious Diseases
Conditions
Keywords
Pediatrics, Safety, Musculoskeletal System, Neurologic Manifestations, Joint Diseases, Joint Deformities, Acquired
Brief summary
Objective and subjective musculoskeletal evaluations will be performed to determine differences in the ciprofloxacin versus non-quinolone treated pediatric patients so that we can tell what the natural occurrence of such musculoskeletal conditions is in the general pediatric population.
Detailed description
This study is classified as interventional due to study-specific medical examinations and interventions. Regarding the study drug intake, routine administration is observed only, there is no intervention in study drug administration.
Interventions
DRUGCiprofloxacin
Either as oral suspension, oral tablets or sequential intravenous (IV) - oral therapy or purely IV therapy according to label
DRUGNon-quinolone antibiotic
Common used dose and route
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 16 Years
Healthy volunteers
No
Inclusion criteria
* Patient is \>/= 2 months of age through 16 years of age * A parent/caregiver must sign an informed consent * Patient must provide assent, as appropriate based on local institutional review board guidelines
Exclusion criteria
* Patients presenting with the following conditions: * exacerbations of cystic fibrosis (CF) * meningitis * Brain abscess * bacterial endocarditis, * Bone and joint infections * having any of the following conditions but lacking a personal history may be admitted to the trial: * Arthritis * Juvenile rheumatoid arthritis (JRA) * Rheumatoid arthritis (RA) * Systemic lupus erythematosis (SLE) * History of rheumatic fever * Psoriasis * Inflammatory bowel disease * Osteoarthritis (OA) * Known underlying rheumatological disease, joint problems known to be associated with arthropathy. * Patients with any pre-treatment baseline musculoskeletal exam abnormalities * Known risk of experiencing seizures, a history of any convulsive disorders * Requiring any concomitant therapeutic course of systemic antibacterial agent * Participation in any industry-sponsored clinical drug development study within one month prior to this study * Known significant liver impairment (ALAT/ASAT and/or baseline bilirubin \> 3 times upper limit of normal) * Known significant renal insufficiency (calculated creatinine clearance of \< 30 ml/min/1.73 m²) * Are pregnant or lactating, or are sexually active and using unreliable contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Arthropathy (Cumulative) | 4-6 weeks after treatment / 1 year after treatment / 2 or 5 years after treatment | Arthropathy, as assessed by independent safety committee. The committee, after reviewing data related to musculoskeletal events, decided whether each patient had arthropathy or not. Each incidence includes number shown at previous time point, plus any new patients with the event. The 112/20 arthropathies are mentioned in the other Adverse Events section as well. |
| Incidence of Nervous System Events (Cumulative) | 4-6 weeks after treatment / 1 year after treatment / 2 or 5 years after treatment | Any event within the MedDRA system organ class 'Nervous System disorders'. Each incidence includes number shown at the previous time point, plus any new patients with the event. |
Countries
Canada, United States
Participant flow
Recruitment details
Observational study in which patients were recruited between 1999 and 2002, and followed up for 5 years (ciprofloxacin patients) or 2 years (non-ciprofloxacin patients), monitoring the occurrence of musculoskeletal and central nervous system events.
Pre-assignment details
The decision to treat with ciprofloxacin or a non-quinolone antibiotic was made prior to a patient's enrollment in the study and was based on the particular infection, type of patient, medical history, and the clinical evaluation by the prescribing physician. The study was not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin Subjects receiving Ciprofloxacin (group followed-up for 5 years) | 487 |
| Non-quinolone Antibiotic Subjects receiving non-quinolone antibiotic (group followed-up for 2 years) | 507 |
| Total | 994 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 2 or 5 Years Long-term Safety Follow-up | Death | 4 | 0 |
| 2 or 5 Years Long-term Safety Follow-up | Lost to Follow-up | 75 | 30 |
| 2 or 5 Years Long-term Safety Follow-up | Withdrawal by Subject | 75 | 21 |
| Treatment | Subjects never received study medication | 23 | 12 |
Baseline characteristics
| Characteristic | Total | Non-quinolone Antibiotic | Ciprofloxacin |
|---|---|---|---|
| Age, Customized >=12 years through 16 years | 77 participants | 19 participants | 58 participants |
| Age, Customized >=13 months through 23 month | 100 participants | 52 participants | 48 participants |
| Age, Customized >= 2 months through 12 month | 85 participants | 48 participants | 37 participants |
| Age, Customized >=2 years through 5 years | 315 participants | 165 participants | 150 participants |
| Age, Customized >= 6 years through 11 years | 417 participants | 223 participants | 194 participants |
| Region of Enrollment Canada | 15 participants | 4 participants | 11 participants |
| Region of Enrollment United States | 979 participants | 503 participants | 476 participants |
| Sex: Female, Male Female | 511 Participants | 242 Participants | 269 Participants |
| Sex: Female, Male Male | 483 Participants | 265 Participants | 218 Participants |
| Type of infection, pre-treatment Category 10, External Otitis | 11 participants | 1 participants | 10 participants |
| Type of infection, pre-treatment Category 11, Wound Infection | 9 participants | 2 participants | 7 participants |
| Type of infection, pre-treatment Category 12, Other Respiratory Tract Infection | 8 participants | 6 participants | 2 participants |
| Type of infection, pre-treatment Category 13, Bacteremia | 7 participants | 1 participants | 6 participants |
| Type of infection, pre-treatment Category 14, Shigellosis | 7 participants | 0 participants | 7 participants |
| Type of infection, pre-treatment Category 15, Acute Bronchitis | 7 participants | 5 participants | 2 participants |
| Type of infection, pre-treatment Category 16, Pseudomonas Infections | 6 participants | 0 participants | 6 participants |
| Type of infection, pre-treatment Category 17, Abscess with cellulitis | 6 participants | 4 participants | 2 participants |
| Type of infection, pre-treatment Category 18, Mastoiditis | 5 participants | 0 participants | 5 participants |
| Type of infection, pre-treatment Category 19, Cystitis | 5 participants | 0 participants | 5 participants |
| Type of infection, pre-treatment Category 1, Otitis Media | 350 participants | 207 participants | 143 participants |
| Type of infection, pre-treatment Category 20, Other | 82 participants | 29 participants | 53 participants |
| Type of infection, pre-treatment Category 2, Pharyngitis / Tonsillitis | 187 participants | 148 participants | 39 participants |
| Type of infection, pre-treatment Category 3, Urinary Tract | 117 participants | 12 participants | 105 participants |
| Type of infection, pre-treatment Category 4, Sinusitis | 86 participants | 47 participants | 39 participants |
| Type of infection, pre-treatment Category 5, Pyelonephritis | 32 participants | 8 participants | 24 participants |
| Type of infection, pre-treatment Category 6, Pneumonia | 29 participants | 17 participants | 12 participants |
| Type of infection, pre-treatment Category 7, Bronchitis | 14 participants | 7 participants | 7 participants |
| Type of infection, pre-treatment Category 8, Abscess | 13 participants | 6 participants | 7 participants |
| Type of infection, pre-treatment Category 9, Skin Infection | 13 participants | 7 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 206 / 487 | 76 / 507 |
| serious Total, serious adverse events | 25 / 487 | 6 / 507 |
Outcome results
Primary
Incidence of Arthropathy (Cumulative)
Arthropathy, as assessed by independent safety committee. The committee, after reviewing data related to musculoskeletal events, decided whether each patient had arthropathy or not. Each incidence includes number shown at previous time point, plus any new patients with the event. The 112/20 arthropathies are mentioned in the other Adverse Events section as well.
Time frame: 4-6 weeks after treatment / 1 year after treatment / 2 or 5 years after treatment
Population: Patients valid for safety (all patients confirmed to have received at least one dose of study drug)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin | Incidence of Arthropathy (Cumulative) | 4-6 weeks after treatment | 39 participants |
| Ciprofloxacin | Incidence of Arthropathy (Cumulative) | 1 year after treatment | 64 participants |
| Ciprofloxacin | Incidence of Arthropathy (Cumulative) | 2 or 5 years after treatment | 112 participants |
| Non-quinolone Antibiotic | Incidence of Arthropathy (Cumulative) | 4-6 weeks after treatment | 9 participants |
| Non-quinolone Antibiotic | Incidence of Arthropathy (Cumulative) | 1 year after treatment | 16 participants |
| Non-quinolone Antibiotic | Incidence of Arthropathy (Cumulative) | 2 or 5 years after treatment | 20 participants |
Primary
Incidence of Nervous System Events (Cumulative)
Any event within the MedDRA system organ class 'Nervous System disorders'. Each incidence includes number shown at the previous time point, plus any new patients with the event.
Time frame: 4-6 weeks after treatment / 1 year after treatment / 2 or 5 years after treatment
Population: Patients valid for safety (all patients confirmed to have received at least one dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ciprofloxacin | Incidence of Nervous System Events (Cumulative) | 1 year after treatment | 49 participants |
| Ciprofloxacin | Incidence of Nervous System Events (Cumulative) | 4-6 weeks after treatment | 38 participants |
| Ciprofloxacin | Incidence of Nervous System Events (Cumulative) | 2 or 5 years after treatment | 56 participants |
| Non-quinolone Antibiotic | Incidence of Nervous System Events (Cumulative) | 1 year after treatment | 13 participants |
| Non-quinolone Antibiotic | Incidence of Nervous System Events (Cumulative) | 4-6 weeks after treatment | 10 participants |
| Non-quinolone Antibiotic | Incidence of Nervous System Events (Cumulative) | 2 or 5 years after treatment | 17 participants |