Clinical trial NCT01207245: Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
Official title: Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC) A Randomized Pharmacokinetic Comparison of Tobramycin in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cystic Fibrosis
Keywords: Cystic fibrosis
Tobramycin
Pharmacokinetics
Toxicity
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2010-09-22
Enrollment: 18
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Renal Elimination Rate Constant of Tobramycin
timeFrame: Days 1, 8 and 14
Secondary outcomes:
measure: Weight
timeFrame: Day 1, 8, 14
measure: Pulmonary Function
timeFrame: Day 1, 8, 14
measure: Urinary Biomarkers
timeFrame: Days 1 and 14
measure: Serum biomarkers
timeFrame: Days 1 & 14
measure: Serum Electrolytes
timeFrame: Days 1 & 14
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: Nottinghamshire
Study officials:
affiliation: University of Nottingham
name: Alan Smyth
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prayle AP, Jain K, Touw DJ, Koch BC, Knox AJ, Watson A, Smyth AR. The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis: A randomised comparison. J Cyst Fibros. 2016 Jul;15(4):510-7. doi: 10.1016/j.jcf.2015.07.012. Epub 2015 Aug 15.