Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC)

• ClinicalTrials.gov Identifier: NCT01207245
• Recruitment Status: Completed
• First Posted: September 22, 2010
• Last Update Posted: June 23, 2015
• Sponsor: University of Nottingham
• Information provided by (Responsible Party): University of Nottingham

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

Locations

United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, United Kingdom, NG7 2UH

Sponsors and Collaborators

University of Nottingham

Investigators

• Principal Investigator: Alan Smyth; University of Nottingham

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Nottingham
• ClinicalTrials.gov 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
• Last Update Posted: June 23, 2015
• Last Verified: June 2015

Keywords provided by University of Nottingham:

Cystic fibrosis; Tobramycin; Pharmacokinetics; Toxicity

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Tobramycin; Anti-Bacterial Agents; Anti-Infective Agents