Clinical trial NCT01543620: Prospective Observational Study to Evaluate Biomarkers of Aminoglycoside Nephrotoxicity in Patients With Cystic Fibrosis
Official title: Prospective Observational Study to Evaluate Biomarkers of Aminoglycoside Nephrotoxicity in Patients With Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cystic Fibrosis
Keywords: kidney safety
biomarkers
serum creatinine
BUN
cystic fibrosis
head and neck cancer
renal injury
drug induced acute kidney injury
aminoglycoside
cisplatin
nephrotoxicity
biomarker qualification
Lead sponsor: Foundation for the National Institutes of Health
Sponsor class: OTHER
Collaborators: name: University of Southern California
name: University of Minnesota
name: M.D. Anderson Cancer Center
name: Dana-Farber Cancer Institute
name: Brigham and Women's Hospital
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Amgen
name: AstraZeneca
name: Eli Lilly and Company
name: Johnson & Johnson
name: Merck Sharp & Dohme LLC
name: Pfizer
name: Critical Path Institute
name: Predictive Safety Testing Consortium
First posted: 2012-03-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: cystic fibrosis patients

Brief summary: The project is designed to test new biomarkers that are more sensitive than the current standard in detecting injury to the proximal kidney tubule and will establish better criteria for when kidney safety concerns may halt further testing of a drug in humans.

Detailed description: The goal of this clinical study is to advance the acceptance of new biomarkers designed to detect drug-induced kidney injury in clinical trials.

The Kidney Safety Project is being conducted at four major medical centers:

* University of Southern California
* University of Minnesota
* MD Anderson Cancer Center
* Dana-Farber Cancer Institute.

Blood and urine samples will be collected from patients undergoing treatment with either cisplatin or aminoglycosides, which are two different drugs known to cause injuries to the proximal tubule of the kidney. Aminoglycosides are a common antibiotic drug taken by patients with cystic fibrosis. Cisplatin is a common chemotherapy drug taken by patients with head and neck cancer.

The Aminoglycoside Study of the Kidney Safety Project is being conducted at the University of Southern California and the University of Minnesota and aims to evaluate aminoglycoside induced acute kidney injury in patients with cystic fibrosis.

The companion study, the Cisplatin Study of the Kidney Safety Project, is being conducted at the MD Anderson Cancer Center and the Dana-Farber Cancer Institute and aims to evaluate cisplatin induced acute kidney injury in patients with head and neck cancer.

The data from the Kidney Safety Project, from both the Aminoglycoside Study and the Cisplatin Study, will be combined for determination of the best biomarkers for predicting drug-induced acute kidney injury.

Eligibility criteria: Inclusion criteria:

1. Males and females ≥ 18 years of age.
2. Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

   * Sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test.
   * Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
   * Abnormal nasal potential difference.
3. Hospitalized and initiated on systemic antibiotic therapy for treatment of an acute pulmonary exacerbation.
4. Willingness and ability to comply with study procedures and study restrictions.
5. Ability to provide written informed consent.

Exclusion criteria:

1. Chronic kidney disease defined by microalbuminuria (\> 30 mcg/mg creatinine) or eGFR \< 60 mL/min/1.73m2.
2. Receiving medications known to alter the tubular secretion of creatinine (e.g. trimethoprim, cimetidine).
3. Hospitalized for treatment of an acute pulmonary exacerbation or received intravenous aminoglycoside antibiotics within 3-months of study entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Minneapolis
country: United States
facility: University of Minnesota - Cystic Fibrosis Center
state: Minnesota
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Southern California
name: Paul Beringer, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Joanne Billings, MD
role: PRINCIPAL_INVESTIGATOR
References: