Drug-Induced Liver Injury (DILN)Network Retrospective (ILIAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00360646
First received: August 2, 2006
Last updated: February 3, 2014
Last verified: February 2014

August 2, 2006
February 3, 2014
September 2004
June 2017   (final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00360646 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Drug-Induced Liver Injury (DILN)Network Retrospective
Idiosyncratic Liver Injury Associated With Drugs (ILIAD): A Retrospective Study

The purpose of this study is to establish retrospectively a nationwide registry of patients who have suffered drug-induced liver injury (DILI), and to collect, immortalize and store serum, DNA, and lymphocytes from these patients. ILIAD will serve as a resource for subsequent mechanistic investigations into the basis of severe idiosyncratic DILI. The primary goal of the ILIAD protocol is to create: (a) a clinical database consisting of individuals who have experienced severe DILI caused by four specific drugs, and the relevant clinical data concerning the episode of DILI; and, (b) to create a bank of biological specimens obtained from these individuals. These biological specimens will be DNA, plasma, and immortalized lymphocytes. Immortalized lymphocytes will provide unlimited amounts of genomic DNA for study as well as living immune cells for phenotyping studies. A secondary goal of the ILIAD protocol is to maintain a registry of cases in the ILIAD database so that they may be recontacted in the future. It is expected that this will facilitate additional studies exploring the mechanisms of DILI.

Drug-induced liver injury (DILI) is the single most common reason for regulatory actions concerning drugs, including failure to gain approval for marketing, removal from the market place, and restriction of prescribing indications. DILI is also a significant cause of morbidity and mortality in many patient populations. To stimulate and facilitate research into DILI, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has recently established the Drug-Induced Liver Injury Network (DILIN). One of the initial projects to be conducted by the network is to retrospectively establish a nationwide registry of patients who have suffered severe idiosyncratic liver injury associated with drugs (ILIAD), and to collect, immortalize and store serum, DNA, and lymphocytes from these patients (hereafter referred to as the "ILIAD protocol"). This ILIAD protocol will serve as a resource for subsequent mechanistic investigations of the basis for susceptibility to severe idiosyncratic DILI.

The network will initially identify people who have developed jaundice as a result of treatment with valproic acid, isoniazid, phenytoin, combination clavulanic acid / amoxicillin, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics. In the case of valproic acid, eligibility requires a clinical presentation that is severe enough to prompt hospitalization or is associated with significant biochemical liver dysfunction.

The specific aims are as follows:

  1. Establish and maintain a clinical database of these people that contains relevant clinical data. The target enrollment will be 50-100 individuals with DILI due to each drug.
  2. Establish a bank of biological specimens (serum, DNA, and immortalized lymphocytes) prepared from cases and control in the clinical database.
  3. Maintain a registry including yearly updated contact information of the subjects enrolled in the clinical database so that it is possible to recontact these individuals at a later date to offer participation in studies which are not part of the current proposal.
Observational
Observational Model: Case Control
Time Perspective: Retrospective
Not Provided
Retention:   Samples With DNA
Description:

Samples with DNA

Non-Probability Sample

Patients with liver injury ascribed to isoniazid, phenytoin, clavulanic acid/amoxicillin, valproic acid, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics

Drug Induced Liver Injury
Not Provided
  • Subjects with liver injury
  • Subjects without liver injury
Rochon J, Protiva P, Seeff LB, Fontana RJ, Liangpunsakul S, Watkins PB, Davern T, McHutchison JG; Drug-Induced Liver Injury Network (DILIN). Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury. Hepatology. 2008 Oct;48(4):1175-83.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
June 2017
June 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

Screening Criteria

To be included in the ILIAD registry, the following criteria must be satisfied:

  • The treating gastroenterologist / hepatologist or health care professional must believe that the subject suffered drug-induced liver injury;
  • The subject must be alive and the date of onset of the qualifying DILI episode must have occurred on or after January 1, 1994;
  • The implicated medication is one of the following: isoniazid, phenytoin, combination clavulanic acid / amoxicillin,valproic acid, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics;
  • The subject is taking only one of these medications in the period leading up to the onset of the qualifying DILI episode;
  • For INH, phenytoin, clavulanic acid / amoxicillin, trimethoprim-sulfamethoxazole, or quinolone antibiotics, total serum bilirubin > 2.5 mg/dL;
  • For nitrofurantoin or minocycline, total serum bilirubin > 2.5 mg/dL or documented fibrosis/cirrhosis on liver biopsy;
  • For valproic acid, compatible symptomatic clinical presentation that is severe enough to prompt hospitalization, or that is associated with significant biochemical liver dysfunction, defined as any of the following:

    1. INR > 1.5
    2. Serum AST or ALT > 3 x the baseline level, if the baseline level is elevated.
    3. Bilirubin >1 x ULN or > 1 x the baseline level, if the baseline level is elevated
    4. Unexplained elevated arterial or venous NH3 levels
    5. Liver biopsy showing steatosis
  • Sufficient documentation of the event for the Causality Committee to make a determination.

Exclusion Criteria:

Subjects will be excluded according to the following criteria:

  • are not willing to have medical information and blood samples taken;
  • are unable to adequately give informed consent to participate in the study including the blood draw for the genetic component;
  • age < 2 years old at the time of study enrollment (due to blood volume requirements).
  • are diagnosed with a specific seizure syndrome associated with known genetic defects if the implicated drug is valproate or phenytoin.
Both
2 Years and older
No
Contact: Kathy M Galan, RN 919-668-8579 Galan006@mc.duke.edu
Contact: Nidia Rosado 305-974-0424 nidia.rosado@duke.edu
United States
 
NCT00360646
Pro00017208, 2U01-DK065176-11Revised+, Pro00011992
Yes
Duke University
Duke University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Huiman X. Barnhart, PhD Duke University
Study Chair: Paul Watkins, MD University of North Carolina, Chapel Hill
Duke University
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP