Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC)
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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 |
- Renal Elimination Rate Constant of Tobramycin [ Time Frame: Days 1, 8 and 14 ] [ Designated as safety issue: Yes ]
- 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 |
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| Contact: Alan R Smyth, MD | 01158230612 | alan.smyth@nottingham.ac.uk |
| 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 | |
| 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 Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn |
Infant, Newborn, Diseases Pathologic Processes Tobramycin Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 23, 2013