Trial Summary  

Study Design: Multi-centre randomised, controlled, open-label, phase IIa trial of rosuvastatin in children with cystic fibrosis throughout a clinically-indicated course of treatment with an IV aminoglycoside.

Population: Children with cystic fibrosis aged 10 to 18 years receiving clinically indicated treatment with intravenous aminoglycoside, and who fulfil the inclusion criteria.

Criteria for Inclusion:

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.

6.       Able to take tablets

  Criteria for Exclusion:

1.       Existing treatment with a statin.

2.       Previous adverse reaction to a statin.

3.    Co-enrolment in other drug trials*, or completion of a previous CTIMP within the last 30 days.

4.     Previous randomisation in the PROteKT trial.

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 and Simepravir.

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<60ml/min/1.73m², using the Schwartz formula, in the 6 months preceding screening).

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 glucose-galactose malabsorption.

15.   Patients who are Hepatitis C positive or HIV-Positive

  *Patients who are currently taking part in TORPEDO-CF are allowed take part in PROteKT as long as their date of randomisation into TORPEDO-CF is not within the previous six months.

  Study Centres and Distribution: Paediatric cystic fibrosis centres in the UK

  Study Duration: 24 months

  Description of Agent/ Intervention: Oral rosuvastatin 10mg once daily.

  Number of participants to be enrolled: Up to 50 participants will be enrolled to account for loss to follow-up. A minimum of 20 participants in each arm of the study is required.

  Primary Objective: This trial will evaluate the effect of rosuvastatin on aminoglycoside-induced nephrotoxicity. This will be assessed using the difference in mean fold-change in urinary KIM-1 from baseline to peak concentration during exposure to aminoglycoside between the rosuvastatin treated arm and control arm.

  Secondary Objective/s:

  1. Change in serum concentration of creatinine and eGFR during tobramycin exposure between rosuvastatin treated arm and the control arm.
  2. Change in other urinary and plasma biomarkers of renal injury during tobramycin exposure between rosuvastatin treated arm and the control arm.
  3. Difference in serious adverse events between rosuvastatin treated arm and the control arm.
  4. Difference in tobramycin concentrations between rosuvastatin treated arm and the control arm to identify any pharmacokinetic interaction between rosuvastatin and the tobramycin.
  5. Difference in Forced Expiratory Volume in 1 second (FEV1) and C-Reactive Protein, between rosuvastatin treated arm and the control arm to identify any pharmacodynamics interaction between rosuvastatin and the tobramycin.
  6. Assessment of plasma rosuvastatin concentrations achieved in children randomised to the intervention arm.
  7. Difference in biomarkers of Pseudomonas aeruginosa between rosuvastatin treated arm and the control arm.
  8. Assess the feasibility of collecting DNA for a molecular genetic study of aminoglycoside-induced nephrotoxicity.

PROteKT
 
 




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