Trial of Rosuvastatin for the Prevention of Kidney Toxicity caused by Tobramycin in Children with Cystic Fibrosis

Phase IIa, Randomised, Controlled, Open-Label Trial of Rosuvastatin for the Prevention of Aminoglycoside-Induced Kidney Toxicity in Children with Cystic Fibrosis - PROteKT

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-002387-32-GB

Enrollment

Registered

2014-06-27

Start date

2014-08-05

Completion date

Unknown

Last updated

2018-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aminoglycoside-induced nephrotoxicity MedDRA version: 18.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 18.0 Level: PT Classification code 10069022 Term: Kidney injury molecule-1 System Organ Class: 10022891 - Investigations MedDRA version: 18.0 Level: LLT Classification code 10067571 Term: Nephrotoxicity System Organ Class: 100000004857

Interventions

Trade Name: Crestor Product Name: Crestor Pharmaceutical Form: Film-coated tablet INN or Proposed INN: Rosuvastatin calcium CAS Number: 287714-41-4 Concentration unit: mg milligram(s) Concentration ty

Eligibility

Sex/Gender

All

Inclusion criteria

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. 6. Able to take tablets. Are the trial subjects under 18? yes Number of subjects for this age range: 45 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: 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 (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 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 glucose-galactose malabsorption. 15. Patients who are Hepatitis C positive or HIV-positive. *Patients who are currently taking part in TORPEDO-CF are allowed to take part in PROteKT as long as their date of randomisation into TORPEDO-CF is not within the previous six months of the screening date for PROteKT.

Design outcomes

Primary

Measure	Time frame
Main Objective: Does rosuvastatin protect against kidney damage caused by aminoglycoside antibiotics? This will be assessed by comparing the difference in the change in the urine biomarker KIM-1 from baseline to 'highest concentration' concentration during exposure to tobramycin between the rosuvastatin treated arm and control arm. ;Secondary Objective: 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 ;Primary end point(s): The primary outcome measure is difference in mean fold-change in urinary KIM-1 from baseline to 'highest concentration' concentration during exposure to tobramycin between the rosuvastatin treated arm and control arm. ;Timepoint(s) of evaluation of this end point: Urine samples, for measurement of urinary KIM-1, will be collected from each child at baseline, and on each day of aminoglycoside treatment (usually lasting 2 weeks). A further sample will be collected at the 4 week follow-up visit.	—

Measure

Time frame

Main Objective: Does rosuvastatin protect against kidney damage caused by aminoglycoside antibiotics? This will be assessed by comparing the difference in the change in the urine biomarker KIM-1 from baseline to 'highest concentration' concentration during exposure to tobramycin between the rosuvastatin treated arm and control arm. ;Secondary Objective: 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 ;Primary end point(s): The primary outcome measure is difference in mean fold-change in urinary KIM-1 from baseline to 'highest concentration' concentration during exposure to tobramycin between the rosuvastatin treated arm and control arm. ;Timepoint(s) of evaluation of this end point: Urine samples, for measurement of urinary KIM-1, will be collected from each child at baseline, and on each day of aminoglycoside treatment (usually lasting 2 weeks). A further sample will be collected at the 4 week follow-up visit.

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Secondary

Measure	Time frame
Secondary end point(s): 1. Difference in serum concentration of creatinine and eGFR during tobramycin exposure between rosuvastatin treated arm and the control arm. 2. Difference 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. Relationship between plasma rosuvastatin concentrations achieved in children randomised to the intervention arm and change in urinary KIM-1. 7. Difference in biomarkers of Pseudomonas aeruginosa between rosuvastatin treated arm and the control arm. ;Timepoint(s) of evaluation of this end point: Blood samples, for secondary endpoints 1, 2, 4, 5, 6, and 7, will be collected at baseline (T0), T+1 day, T+8 days, T+13 days, and the 4 week follow-up visits. Urine samples, for secondary endpoints 2 and 7, will be collected at baseline, on each day of aminoglycoside treatment (usually lasting 2 weeks), and the 4 week follow-up visit. FEV1, for secondary endpoint 5, will be measured at baseline (T0), T+8 days, T+13 days, and the 4 week follow-up visits.	—

Measure

Time frame

Secondary end point(s): 1. Difference in serum concentration of creatinine and eGFR during tobramycin exposure between rosuvastatin treated arm and the control arm. 2. Difference 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. Relationship between plasma rosuvastatin concentrations achieved in children randomised to the intervention arm and change in urinary KIM-1. 7. Difference in biomarkers of Pseudomonas aeruginosa between rosuvastatin treated arm and the control arm. ;Timepoint(s) of evaluation of this end point: Blood samples, for secondary endpoints 1, 2, 4, 5, 6, and 7, will be collected at baseline (T0), T+1 day, T+8 days, T+13 days, and the 4 week follow-up visits. Urine samples, for secondary endpoints 2 and 7, will be collected at baseline, on each day of aminoglycoside treatment (usually lasting 2 weeks), and the 4 week follow-up visit. FEV1, for secondary endpoint 5, will be measured at baseline (T0), T+8 days, T+13 days, and the 4 week follow-up visits.

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Countries

United Kingdom

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 25, 2026