Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC)

University of Nottingham

Status and phase: Completed; Phase 4

Conditions: Cystic Fibrosis

Treatments: Other: Tobramycin time of administration

Study type: Interventional

Funder types: Other

Identifiers

NCT01207245

NIHR RfPB PB-PG-1207-15025 (Other Grant/Funding Number)

10076 (Other Identifier)

Details and patient eligibility

About

Cystic fibrosis is the most common inherited life limiting condition which affects children. Patients with it develop lung infections which become difficult to clear, and damage the lungs. These are treated with antibiotics (such as tobramycin) into the vein (termed "intravenous antibiotics"). This has without doubt improved survival. However, all treatments have side effects. Tobramycin can cause kidney damage. The investigators have preliminary data that suggests that administering tobramycin in the morning may be safer for the kidneys than administering it in the evening.

The investigators plan to approach children and adults with cystic fibrosis whose doctors have decided to administer a course of intravenous tobramycin. The investigators will randomly allocate them to receive it at either 0800h or 2200h. The investigators will measure the rate at which the body eliminates tobramycin from the bloodstream, by measuring the amount of tobramycin in the blood stream after administering the antibiotic. For each patient the study will last for the duration of the course of antibiotics. This is decided by the doctor looking after the patient (rather than the researcher), and would typically be 14 days. The investigators will also measure substances in the blood and urine ("biomarkers") which are sensitive indicators of low levels of kidney injury. The investigators will monitor lung function and lung bacteria in both the groups to ensure that the patients in both groups improve by the same amount.

If the preliminary data are proved correct, this research will allow investigators to improve the safety profile of tobramycin, one of the most widely prescribed drugs in cystic fibrosis.

Enrollment: 18 patients

Sex: All

Ages: 5+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of cystic fibrosis (CF) (defined as clinical features of CF plus a positive sweat test OR the presence of 2 genes known to be associated with CF disease)
• Males or female 5 years and older
• Treating doctor has decided to commence a course of tobramycin
• Patient or parent / legal guardian able to give informed consent

Exclusion criteria

• Previous episode of acute kidney injury
• Solid organ transplantation
• Evidence of impaired renal function (raised serum creatinine above the normal range for age)
• Once daily aminoglycoside unsuitable because of hypersensitivity or previous high trough levels on once daily dosing.
• Pregnancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 2 patient groups

Morning dose of tobramycin

Active Comparator group

Description:

Administration of tobramycin once daily dose in the morning

Treatment:

Other: Tobramycin time of administration

Evening tobramycin

Active Comparator group

Description:

Evening dose of tobramycin once daily

Treatment:

Other: Tobramycin time of administration