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Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC)

This study has been completed.
Information provided by (Responsible Party):
University of Nottingham Identifier:
First received: September 21, 2010
Last updated: June 22, 2015
Last verified: June 2015

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.

Condition Intervention Phase
Cystic Fibrosis
Other: Tobramycin time of administration
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC) A Randomized Pharmacokinetic Comparison of Tobramycin in Cystic Fibrosis

Resource links provided by NLM:

Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Renal Elimination Rate Constant of Tobramycin [ Time Frame: Days 1, 8 and 14 ]

Secondary Outcome Measures:
  • Weight [ Time Frame: Day 1, 8, 14 ]
  • Pulmonary Function [ Time Frame: Day 1, 8, 14 ]
  • Urinary Biomarkers [ Time Frame: Days 1 and 14 ]
    NAG, NGAL, IL-18, KIM1, Cystatin C

  • Serum biomarkers [ Time Frame: Days 1 & 14 ]
    Serum creatinine Serum Cystatin C Estimated GFR

  • Serum Electrolytes [ Time Frame: Days 1 & 14 ]
    Serum Potassium and Magnesium

Enrollment: 18
Study Start Date: May 2011
Study Completion Date: June 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morning dose of tobramycin
Administration of tobramycin once daily dose in the morning
Other: Tobramycin time of administration
Random allocation to time of day of administration of tobramycin
Active Comparator: Evening tobramycin
Evening dose of tobramycin once daily
Other: Tobramycin time of administration
Random allocation to time of day of administration of tobramycin


Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01207245

United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Principal Investigator: Alan Smyth University of Nottingham
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Nottingham Identifier: NCT01207245     History of Changes
Other Study ID Numbers: 10076
NIHR RfPB PB-PG-1207-15025 ( Other Grant/Funding Number: National Institute of Health Research )
Study First Received: September 21, 2010
Last Updated: June 22, 2015

Keywords provided by University of Nottingham:
Cystic fibrosis

Additional relevant MeSH terms:
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Anti-Bacterial Agents
Anti-Infective Agents processed this record on April 25, 2017