Rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis
| ISRCTN | ISRCTN26104255 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN26104255 |
| EudraCT/CTIS number | 2014-002387-32 |
| Secondary identifying numbers | 16993 |
- Submission date
- 05/09/2014
- Registration date
- 05/09/2014
- Last edited
- 21/06/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Cystic fibrosis is a genetic condition where the lungs and digestive system gets clogged with thick sticky mucus. Many children with cystic fibrosis (CF) have treatment with an antibiotic called tobramycin given straight into the blood stream (called intravenous or IV). This helps treat their lung infections, but it can sometimes cause kidney problems. We think that giving a medicine called rosuvastatin at the same time as tobramycin could help protect the kidneys from damage and make it safer to give tobramycin. To help us find out whether this is true or not, we are doing a research study called a clinical trial in children with CF getting IV tobramycin where half of the children taking part also get rosuvastatin, and the other half do not.
Who can participate?
Children aged 10 to 18 years with cystic fibrosis.
What does the study involve?
At the first visit each child will be randomly allocated to their treatment group for the study. There is an equal chance of being in either group. One group will take a rosuvastatin tablet each day they are having IV tobramycin, and the other group will just have their IV tobramycin as normal. Each child will be in the study for about 6 weeks and will normally have five visits as part of the study. As much as possible we will do the study visits and blood tests at the same time as they would normally have them. However, the study will usually mean having two more blood tests and visits than normal, and we will take a little more blood than usual each time. There will be study visits on the day of starting IV tobramycin, on three further occasions during the course of treatment (usually 14 days), and 4 weeks after completing treatment. In addition, daily urine samples will be collected during the course of tobramycin.
What are the possible benefits and risks of participating?
Like any medicine, rosuvastatin can have side effects. Rarely, it can have serious effects on the liver or muscles. These, and other possible side effects, will be explained to potential participants before agreeing to the study. We will monitor each child very closely for any side effects during the study. If the study shows that rosuvastatin does protect the kidneys, then there may be a benefit to the children who take part, and the study may help children and young people in the future. However, we will not be able to continue prescribing rosuvastatin at the end of the study, even if they have benefitted from it.
Where is the study run from?
The study is run by the University of Liverpool and University College London, and will be recruiting participants at the following hospitals in the UK: Alder Hey Childrens Hospital, Liverpool, Great Ormond Street Hospital, Nottingham Childrens Hospital, and Bristol Royal Hospital for Children.
When is the study starting and how long is it expected to run for?
October 2014 to September 2016.
Who is funding the study?
The JP Moulton Charitable Foundation (UK).
Who is the main contact?
Dr Stephen McWilliam
stevemcw@liv.ac.uk
Contact information
Scientific
Alder Hey Hospital
Eaton Road West Derby
Liverpool
L12 2AP
United Kingdom
| stevemcw@liv.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Phase IIa, randomised, controlled, open-label trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis |
| Study acronym | PROteKT |
| Study objectives | Does co-administration of rosuvastatin prevent kidney toxicity caused by aminoglycoside antibiotics in children with cystic fibrosis? |
| Ethics approval(s) | 14/NW/1067; First MREC approval date 05/08/2014 |
| Health condition(s) or problem(s) studied | Topic: Children; Subtopic: All Diagnoses; Disease: All Diseases |
| Intervention | Patients will be randomised equally to either receive rosuvastatin 10 mg once daily or no intervention (control), throughout a course of treatment with IV tobramycin (usually lasting 14 days). Study visits will be conducted on the day of starting IV tobramycin, on three further occasions during the course of treatment (usually 14 days), and 4 weeks after completing treatment. In addition, daily urine samples will be collected during the course of tobramycin. |
| Intervention type | Other |
| Primary outcome measure | Mean fold-change in urinary KIM-1; Timepoint(s): Urinary KIM-1 measured daily during tobramycin exposure. This will be assessed using the difference in mean fold-change in urinary KIM-1 from baseline to peak concentration during exposure to tobramycin between the rosuvastatin-treated arm and control arm. |
| Secondary outcome measures | Not provided at time of registration |
| Overall study start date | 01/10/2014 |
| Completion date | 01/09/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 10 Years |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 50; UK Sample Size: 50 |
| Total final enrolment | 50 |
| Key inclusion criteria | 1. Age 10 to 18 years inclusive 2. Diagnosis of cystic fibrosis (established by sweat test or genotype) 3. Planned, clinically indicated, course of treatment with IV tobramycin 4. Ability to give informed consent 5. Willingness to comply with all study requirements. |
| Key exclusion criteria | 1. Unable to take tablets 2. Existing treatment with a statin 3. Previous adverse reaction to a statin 4. Coenrolment in other drug trials, or completion of a previous CTIMP within the last 30 days 5. Patients taking any of the following medications: ciclosporin, protease inhibitors, fibrates, ezetimibe, erythromycin (but not other macrolides), eltrombopag, dronedarone, itraconazole, coumarins, oral contraceptives, nicotinic acid, fusidic acid 6. Female participants who are pregnant or lactating or refuse a pregnancy test if of childbearing potential (female participants of childbearing potential must use a barrier method of contraception if sexually active whilst taking rosuvastatin and for 7 days afterwards) 7. Patients of Asian ancestry (Japanese, Chinese, Filipino, Vietnamese, Korean and Indian). 8. Patients with renal disease (eGFR < 60 ml/min/1.73sq. m, using the Schwartz formula, in the 6 months preceding randomisation) 9. Patients with current elevation in transaminases exceeding 3x the upper limit of normal 10. Family history, or personal history, of hereditary muscular disorders 11. Patients with myopathy 12. Patients with a history of, or active alcohol abuse 13. Patients with hypothyroidism 14. Patients with galactose intolerance, the Lapp lactase deficiency, or glucosegalactose malabsorption |
| Date of first enrolment | 01/10/2014 |
| Date of final enrolment | 01/09/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
L12 2AP
United Kingdom
Sponsor information
University/education
Department of Clinical Psychology
Thompson Yates Building
Quadrangle Brownlow Hill
Liverpool
L69 3GB
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 31/05/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 21/06/2019 | No | No | ||
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
21/06/2019: Added clinicaltrialsregister.eu link to basic results (scientific). Added total final enrollment.
29/01/2019: The intention to publish date has been added
