Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— CRITIC  

Official title:

Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis (CRITIC) A Randomized Pharmacokinetic Comparison of Tobramycin in Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01207245
• Other study ID #: 10076
• Secondary ID: NIHR RfPB PB-PG-
• Status: Completed
• Phase: Phase 4
• First received: September 21, 2010
• Last updated: June 22, 2015
• Start date: May 2011
• Est. completion date: June 2012

Study information

• Verified date: June 2015
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Other:
• Tobramycin time of administration
Random allocation to time of day of administration of tobramycin

Locations

Country	Name	City	State
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	Nottinghamshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Elimination Rate Constant of Tobramycin		Days 1, 8 and 14	Yes
Secondary	Weight		Day 1, 8, 14	No
Secondary	Pulmonary Function		Day 1, 8, 14	No
Secondary	Urinary Biomarkers	NAG, NGAL, IL-18, KIM1, Cystatin C	Days 1 and 14	Yes
Secondary	Serum biomarkers	Serum creatinine Serum Cystatin C Estimated GFR	Days 1 & 14	Yes
Secondary	Serum Electrolytes	Serum Potassium and Magnesium	Days 1 & 14	Yes