The Drug Induced Renal Injury Consortium

Acute Kidney Injury Clinical Trial

— DIRECT  

Official title:

The Genetic Contribution to Drug Induced Renal Injury: The Drug Induced Renal Injury Consortium (DIRECT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02159209
• Other study ID #: 121651
• Status: Completed
• Phase: N/A
• First received: September 26, 2013
• Last updated: April 19, 2016
• Start date: February 2013
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Observational

Clinical Trial Summary

Some medications are known to cause kidney damage because the person is allergic to the medication while others cause direct damage to the kidney because they are toxic at certain concentrations. Risk factors for developing kidney damage have been identified for some medications but not for all. Patients who are exposed to these important medications and develop problems with their kidneys may have some genetic risk. The purpose of this study is to determine the genetic risk factors for drug induced kidney injury. A better understanding of the role of genetics for the development of kidney injury from medications will allow us to better select medications, improve effectiveness of treatment and minimize harm.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 634
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• Patients age 2 years and older

• Exposure to a candidate drug for at least 24 hours (see above)

• Patients who have developed DIRI as defined by the primary criteria

• Written informed consent or assent and consent obtained

• If patient lacks capacity to consent then surrogate consent will be obtained

Exclusion Criteria:

• Patients with a history of or have a kidney transplant

• Patients with a history of or have a bone marrow transplant

• Patients with Chronic Kidney Disease stage 5 (eGFR < 15 mL/min/1.73m2)

• Patients on 3 or more causal drugs

• Patients with no history or time course on drug exposure

• Patient who, in the opinion of the Investigator, is not suitable to participate in the study.

• Unable to obtain written informed consent or assent

• Unable to obtain surrogate consent for patients who lack capacity

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Kidney Failure
• Acute Kidney Injury
• Adverse Drug Reaction
• Drug-Related Side Effects and Adverse Reactions
• Kidney Disease
• Kidney Diseases
• Kidney Failure
• Renal Insufficiency

Locations

Country	Name	City	State
Bolivia	Universidad del Valle, Cochabamba	Cochabamba
Canada	Hopital Sacre Coeur & Universite de Montreal	Montreal	Quebec
Chile	Universidad de Los Andes	Santiago
India	CARE Hospitals	Banjara Hills	Hyderabad
India	Postgraduate Institute of Research, Chandigarh	Chandigarh
United Kingdom	St James's University Hospital	Leeds	West Yorkshire
United Kingdom	Guy's & St Thomas's Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Newcastle University	Newcastle upon Tyne	Tyne and Wear
United Kingdom	University of Nottingham	Nottingham
United States	St. Peter's Hospital	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Jacobi Medical Center	New York	New York
United States	Rady Children's Hospital	San Diego	California
United States	University of California, San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Ravindra Mehta	International Serious Adverse Event Consortium

Countries where clinical trial is conducted

United States,  Bolivia,  Canada,  Chile,  India,  United Kingdom, 

References & Publications (1)

Mehta RL, Awdishu L, Davenport A, Murray PT, Macedo E, Cerda J, Chakaravarthi R, Holden AL, Goldstein SL. Phenotype standardization for drug-induced kidney disease. Kidney Int. 2015 Aug;88(2):226-34. doi: 10.1038/ki.2015.115. Epub 2015 Apr 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identify genes that predispose to dose dependent (Type A) or hypersensitivity (Type B) during drug induced nephrotoxicity.	Blood Draw (20 cc) and urine collection (80cc)	At time of enrollment	No
Secondary	To identify specific alterations in drug metabolism pathways that contribute to drug induced renal injury with different drugs.	We will perform a GWAS to examine the association of common genetic variants with the development of DIRI. For assessing association between a common SNP and the risk of DIRI, association tests will be undertaken to compare genotype frequencies between cases and controls. We will use logistic regression models under the assumption of an additive genetic model and incorporate potential confounders and covariates. Dominant, recessive models will also be checked through alternative coding of the genotype for SNPs approaching significance.	DNA sample collected at time of enrollment.	No