Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis

NCT01207245 | Completed Phase 4 DMC

• 2 other identifiers: 10076NIHR RfPB PB-PG-1207-15025
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Keywords

Cystic fibrosis; Tobramycin; Pharmacokinetics; Toxicity

Outcome Measures

Primary Outcomes (1)

• Renal Elimination Rate Constant of Tobramycin

  Days 1, 8 and 14

Secondary Outcomes (5)

• Weight

  Day 1, 8, 14

• Pulmonary Function

  Day 1, 8, 14

• Urinary Biomarkers

  Days 1 and 14

• Serum biomarkers

  Days 1 & 14

• Serum Electrolytes

  Days 1 & 14

Study Arms (2)

Morning dose of tobramycin

ACTIVE COMPARATOR

Administration of tobramycin once daily dose in the morning

Other: Tobramycin time of administration

Evening tobramycin

ACTIVE COMPARATOR

Evening dose of tobramycin once daily

Other: Tobramycin time of administration

Interventions

Tobramycin time of administration OTHER

Random allocation to time of day of administration of tobramycin

Evening tobramycin; Morning dose of tobramycin

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26282839 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Alan Smyth

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 22, 2010
• Study Start: May 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: June 23, 2015

Record last verified: 2015-06

Locations

GB (1)