The Drug Induced Renal Injury Consortium (DIRECT)

April 19, 2016 updated by: Ravindra Mehta

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

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.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

634

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bolivia
      • Cochabamba, Bolivia
        • Universidad del Valle, Cochabamba
  • Canada
    • Quebec
      • Montreal, Quebec, Canada
        • Hopital Sacre Coeur & Universite de Montreal
  • Chile
      • Santiago, Chile
        • Universidad de Los Andes
  • India
      • Chandigarh, India
        • Postgraduate Institute of Research, Chandigarh
    • Hyderabad
      • Banjara Hills, Hyderabad, India
        • Care Hospitals
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, United Kingdom, SE1 7EH
        • Guy's & St Thomas's Hospital
      • Nottingham, United Kingdom, NG7 2RD
        • University of Nottingham
    • Tyne and Wear
      • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE1 7RU
        • Newcastle University
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS9 7TF
        • St James's University Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama, Birmingham
    • California
      • San Diego, California, United States, 92103
        • University of California, San Diego
      • San Diego, California, United States, 92123
        • Rady Children's Hospital
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • New York
      • Albany, New York, United States, 12208
        • St. Peter's Hospital
      • New York, New York, United States, 10461
        • Jacobi Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

This is a prospective observational cohort study of patients who have developed DIRI. Patients will be identified through two main approaches;

  1. Recall and review of medical records of patients who were suspected to have DIRI
  2. Concurrent identification of patient under active treatment.

Patients who developed DIRI in their previous care provided will be identified through a review of kidney biopsy logs or nephrology consults previously made.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identify genes that predispose to dose dependent (Type A) or hypersensitivity (Type B) during drug induced nephrotoxicity.
Time Frame: At time of enrollment
Blood Draw (20 cc) and urine collection (80cc)
At time of enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To identify specific alterations in drug metabolism pathways that contribute to drug induced renal injury with different drugs.
Time Frame: 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.
DNA sample collected at time of enrollment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ravindra Mehta

Collaborators

International Serious Adverse Event Consortium

Investigators

  • Principal Investigator: Ravindra Mehta, MD, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

September 26, 2013

First Submitted That Met QC Criteria

June 5, 2014

First Posted (Estimate)

June 9, 2014

Study Record Updates

Last Update Posted (Estimate)

April 21, 2016

Last Update Submitted That Met QC Criteria

April 19, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 121651

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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