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Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by University of Nottingham.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01207245
First received: September 21, 2010
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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
Endpoint Classification: Pharmacokinetics Study
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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Weight [ Time Frame: Day 1, 8, 14 ] [ Designated as safety issue: No ]
  • Pulmonary Function [ Time Frame: Day 1, 8, 14 ] [ Designated as safety issue: No ]
  • Urinary Biomarkers [ Time Frame: Days 1 and 14 ] [ Designated as safety issue: Yes ]
    NAG, NGAL, IL-18, KIM1, Cystatin C

  • Serum biomarkers [ Time Frame: Days 1 & 14 ] [ Designated as safety issue: Yes ]
    Serum creatinine Serum Cystatin C Estimated GFR

  • Serum Electrolytes [ Time Frame: Days 1 & 14 ] [ Designated as safety issue: Yes ]
    Serum Potassium and Magnesium


Estimated Enrollment: 20
Study Start Date: May 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 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

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207245

Contacts
Contact: Alan R Smyth, MD 01158230612 alan.smyth@nottingham.ac.uk

Locations
United Kingdom
Nottingham University Hospitals NHS Trust Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Contact: Andrew P Prayle, BMBS    +44 115 8230623    andrew.prayle@nottingham.ac.uk   
Principal Investigator: Alan R Smyth, MD         
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Alan Smyth University of Nottingham
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01207245     History of Changes
Other Study ID Numbers: 10076, NIHR RfPB PB-PG-1207-15025
Study First Received: September 21, 2010
Last Updated: October 4, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Nottingham:
Cystic fibrosis
Tobramycin
Pharmacokinetics
Toxicity

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014