Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis

NCT ID: NCT01207245

Last Updated: 2015-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2012-06-30

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Morning dose of tobramycin

Administration of tobramycin once daily dose in the morning

Group Type: ACTIVE_COMPARATOR

Tobramycin time of administration

Intervention Type: OTHER

Random allocation to time of day of administration of tobramycin

Evening tobramycin

Evening dose of tobramycin once daily

Group Type: ACTIVE_COMPARATOR

Tobramycin time of administration

Intervention Type: OTHER

Random allocation to time of day of administration of tobramycin

Interventions

Tobramycin time of administration

Random allocation to time of day of administration of tobramycin

Intervention Type: OTHER

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

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alan Smyth

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26282839 (View on PubMed)

Other Identifiers

NIHR RfPB PB-PG-1207-15025

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

10076

Identifier Type: -

Identifier Source: org_study_id