DIRECT: The Drug Induced Renal Injury Consortium

Sponsor

Ravindra Mehta (Other)

Overall Status

Completed

CT.gov ID

NCT02159209

Collaborator

International Serious Adverse Event Consortium (Other)

634

Enrollment

Locations

33.9

Duration (Months)

35.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury Adverse Drug Reaction Acute Kidney Failure Kidney Failure Kidney Disease

Study Design

Study Type:

Observational

Actual Enrollment :

634 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Drug Induced Renal Injury (DIRI) This is a prospective observational cohort study of patients who have developed acute kidney injury Stage 2 or a glomerular disorder following exposure to specific drugs that have been associated with DIRI.

Outcome Measures

Primary Outcome Measures

Identify genes that predispose to dose dependent (Type A) or hypersensitivity (Type B) during drug induced nephrotoxicity. [At time of enrollment]
Blood Draw (20 cc) and urine collection (80cc)

Secondary Outcome Measures

To identify specific alterations in drug metabolism pathways that contribute to drug induced renal injury with different drugs. [DNA sample collected at time of enrollment.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35294
2	University of California, San Diego	San Diego	California	United States	92103
3	Rady Children's Hospital	San Diego	California	United States	92123
4	University of Colorado	Aurora	Colorado	United States	80045
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	St. Peter's Hospital	Albany	New York	United States	12208
7	Jacobi Medical Center	New York	New York	United States	10461
8	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
9	Universidad del Valle, Cochabamba	Cochabamba		Bolivia
10	Hopital Sacre Coeur & Universite de Montreal	Montreal	Quebec	Canada
11	Universidad de Los Andes	Santiago		Chile
12	CARE Hospitals	Banjara Hills	Hyderabad	India
13	Postgraduate Institute of Research, Chandigarh	Chandigarh		India
14	Newcastle University	Newcastle upon Tyne	Tyne and Wear	United Kingdom	NE1 7RU
15	St James's University Hospital	Leeds	West Yorkshire	United Kingdom	LS9 7TF
16	Royal Free Hospital	London		United Kingdom	NW3 2QG
17	Guy's & St Thomas's Hospital	London		United Kingdom	SE1 7EH
18	University of Nottingham	Nottingham		United Kingdom	NG7 2RD