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Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01207245
Recruitment Status : Completed
First Posted : September 22, 2010
Last Update Posted : June 23, 2015
Information provided by (Responsible Party):
University of Nottingham

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Other: Tobramycin time of administration Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : May 2011
Actual Primary Completion Date : May 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
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

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

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

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

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

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01207245

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United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
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Principal Investigator: Alan Smyth University of Nottingham
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Nottingham Identifier: NCT01207245    
Other Study ID Numbers: 10076
NIHR RfPB PB-PG-1207-15025 ( Other Grant/Funding Number: National Institute of Health Research )
First Posted: September 22, 2010    Key Record Dates
Last Update Posted: June 23, 2015
Last Verified: June 2015
Keywords provided by University of Nottingham:
Cystic fibrosis
Additional relevant MeSH terms:
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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