Drug-induced Liver InjuryNCT01584765
Rechallenge, Potential Drug Induced Liver Injury (Kaiser)
An observational study of Drug-induced Liver Injury, run by GlaxoSmithKline.
Trial summary
Drug re-administration or rechallenge should be avoided after drug-induced liver injury (DILI) to avoid recurrent and fatal injury. Rechallenge outcomes vary considerably by drug and patient subjects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug-induced Liver Injury
- What is being tested?
- Prescription drugs with known hepatotoxicity
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- Feb 2012to Apr 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The population was defined as patients 1) 18 years or older at the start of the drug exposure, 2) with 12 months or more of continuous membership plus drug benefit immediately prior to the drug start date, and 3) filling at least one prescription for fourteen drugs associated with hepatotoxicity (Chalasani 2008) anytime between Jan. 1, 2003 to June 30, 2009. Overall, 1,064,722 patients fulfill these criteria as derived from the total study population of the descriptive analysis. To be included in this analysis, patients had to be rechallenged with the same suspect drug and had at least one ALT measured at first exposure and during the rechallenge event. Study observations started in 2002 to allow for a year of pre-study observation in all exposures at risk. Applying all inclusion and exclusion criteria, the total study population comprises of 846 subjects.
Who may be able to join
- Patients who received at least one prescription for a suspect drug between Jan 1, 2003 and June 30, 2009 (drug initiation period)
- Patients who experienced incident DILI event (identified by ALT ≥3xULN or AP ≥2xULN within 6 months of suspect drug administration) during the first exposure period that:
- Resolved to within normal limits of ALT (for hepatocellular \& mixed) or AP (for cholestatic) within 180 days or
- Resolved to ALT < 3xULN (for hepatocellular \& mixed) within 90 days or AP<2xULN (for cholestatic) within 180 days or
- Dropped by ≥50% of (Peak ALT - ULN) for hepatocellular or of (Peak AP - ULN) for cholestatic or mixed within 180 days
- Patients who were rechallenged with the same suspect drug; rechallenge will include first rechallenge event for the analysis.
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- Patients who had at least of 12 months of continuous membership and drug benefit prior to and on the dispensing index date (inclusive). There is no minimum restriction of continuous membership plus drug benefit after the start date.
- Patients who were 18 years of age or older at the time of the first drug dispensing (index date) during the drug initiation period Jan 1, 2003 and June 30, 2009. Each patient's first prescription for the study drugs during the drug initiation period will be identified as index prescription.
- Patients who had health insurance coverage with full medical, pharmacy and lab benefits at the index date.
Who cannot join
- Patients meeting the definition of chronic liver injury and exhibiting persistent ALT≥3xULN or AP or bilirubin ≥2xULN within 90 days after initial injury
- Patients with chronic liver injury diagnostic codes or included in KPSC disease registries preceding the initial or rechallenge liver injury
About this study
Official title: Rechallenge Analysis: Detection of Potential Drug-Induced Liver Injury Using Kaiser California Database
Drug re-administration or rechallenge should be avoided after drug-induced liver injury (DILI) to avoid recurrent and fatal injury. Rechallenge outcomes vary considerably by drug and patient subjects. In order to better predict these outcomes, the objective of this analysis is to assess clinical outcomes of positive drug rechallenge following possible drug-induced liver injury. Electronic medical records from Kaiser Permanente California (KPSC), a managed care organization, will be utilized to identify patients who experience possible drug-induced liver injury following exposure to medications associated with hepatotoxicity, and who are then rechallenged with the medication.
- Conditions
- Drug-induced Liver Injury
- Being tested
- Prescription drugs with known hepatotoxicity
- Keywords
- liver injury, Rechallenge, Kaiser Permanente California
- Medical subject headings
- Chemical and Drug Induced Liver Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prescription drugs with known hepatotoxicityDrug
14 prescription drugs with known hepatotoxicity : Amoxicillin/clavulanate, nitrofurantoin, isoniazid, trimethoprim-sulfamethoxazole, duloxetine, valproate, interferon-beta, ciprofloxacin, lamotrigine, phenytoin, diclofenac, terbinafine, levofloxacin, aripiprazole
| Study group | Role | What they receive |
|---|---|---|
| Rechallenge | positive, negative, indeterminate and intermediate rechallenge subtypes Receives: Drug: Prescription drugs with known hepatotoxicity | |
| Severe positive rechallenge | Subtype of positive rechallenge is defined as: ALT≥5 xULN or AP ≥2 xULN and bilirubin ≥2 xULN with one of the following: INR ≥1.5, Ascites, or Encephalopathy where time from liver chemistry elevation to INR≥1.5,ascites, or encephalopathy is less than 26 weeks in the absence of underlying cirrhosis; other organ failure considered due to DILI; liver-related hospitalization Receives: Drug: Prescription drugs with known hepatotoxicity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver injury rechallenge
Liver injury in relation to rechallenge types (positive, negative, indeterminate and intermediate) for hepatocellular, cholestatic and mixed DILI, respectively, defined according to Danan \& Benichou, 1993, J Clin Epidemiol, 46(11): p. 1323-30.
Measured: Up to seven and a half years
Secondary outcomes (1)
Severe positive rechallenge
Severe positive rechallenge, defined as: ALT≥5 xULN or AP≥2 xULN and bilirubin≥2 xULN with one of the following: INR≥1.5, Ascites, or Encephalopathy where time from liver chemistry elevation to INR≥1.5,ascites, or encephalopathy<26 weeks in the absence of underlying cirrhosis; other organ failure considered due to DILI; or liver-related hospitalization. In subjects not meeting the definition of chronic liver injury and exhibiting persistent ALT≥3xULN or AP or bilirubin ≥2xULN after initial injury, positive drug rechallenge is defined as a doubling of ALT, alkaline phosphatase or bilirubin.
Measured: Up to seven and a half years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2012 (estimated)
- Study startFeb 2012
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug-induced Liver InjuryStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01584765
- Sponsor's protocol ID
- 115983
- Other IDs
- WEUKBRE5538
- Status last verified
- Jul 2014
- First submitted
- 12 Apr 2012
- Last updated
- 8 Jul 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rechallenge Analysis: Detection of Potential Drug-Induced Liver Injury Using Kaiser California Database
- ClinicalTrials.gov ID
- NCT01584765
- Acronym / sponsor ID
- 115983
- Conditions
- Drug-induced Liver Injury
- Keywords
- liver injury, Rechallenge, Kaiser Permanente California
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 25 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Drug re-administration or rechallenge should be avoided after drug-induced liver injury (DILI) to avoid recurrent and fatal injury. Rechallenge outcomes vary considerably by drug and patient subjects. In order to better predict these outcomes, the objective of this analysis is to assess clinical outcomes of positive drug rechallenge following possible drug-induced liver injury. Electronic medical records from Kaiser Permanente California (KPSC), a managed care organization, will be utilized to identify patients who experience possible drug-induced liver injury following exposure to medications associated with hepatotoxicity, and who are then rechallenged with the medication.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rechallenge | – | Drug: Prescription drugs with known hepatotoxicitypositive, negative, indeterminate and intermediate rechallenge subtypes |
| Severe positive rechallenge | – | Drug: Prescription drugs with known hepatotoxicitySubtype of positive rechallenge is defined as: ALT≥5 xULN or AP ≥2 xULN and bilirubin ≥2 xULN with one of the following: INR ≥1.5, Ascites, or Encephalopathy where time from liver chemistry elevation to INR≥1.5,ascites, or encephalopathy is less than 26 weeks in the absence of underlying cirrhosis; other organ failure considered due to DILI; liver-related hospitalization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The population was defined as patients 1) 18 years or older at the start of the drug exposure, 2) with 12 months or more of continuous membership plus drug benefit immediately prior to the drug start date, and 3) filling at least one prescription for fourteen drugs associated with hepatotoxicity (Chalasani 2008) anytime between Jan. 1, 2003 to June 30, 2009. Overall, 1,064,722 patients fulfill these criteria as derived from the total study population of the descriptive analysis. To be included in this analysis, patients had to be rechallenged with the same suspect drug and had at least one ALT measured at first exposure and during the rechallenge event. Study observations started in 2002 to allow for a year of pre-study observation in all exposures at risk. Applying all inclusion and exclusion criteria, the total study population comprises of 846 subjects.
Key inclusion criteria (9 listed)
- Patients who received at least one prescription for a suspect drug between Jan 1, 2003 and June 30, 2009 (drug initiation period)
- Patients who experienced incident DILI event (identified by ALT ≥3xULN or AP ≥2xULN within 6 months of suspect drug administration) during the first exposure period that:
- Patients who were rechallenged with the same suspect drug; rechallenge will include first rechallenge event for the analysis.
- Patients who had at least of 12 months of continuous membership and drug benefit prior to and on the dispensing index date (inclusive). There is no minimum restriction of continuous membership plus drug benefit after the start date.
- Patients who were 18 years of age or older at the time of the first drug dispensing (index date) during the drug initiation period Jan 1, 2003 and June 30, 2009. Each patient's first prescription for the study drugs during the drug initiation period will be identified as index prescription.
Key exclusion criteria (2 listed)
- Patients meeting the definition of chronic liver injury and exhibiting persistent ALT≥3xULN or AP or bilirubin ≥2xULN within 90 days after initial injury
- Patients with chronic liver injury diagnostic codes or included in KPSC disease registries preceding the initial or rechallenge liver injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prescription drugs with known hepatotoxicity14 prescription drugs with known hepatotoxicity : Amoxicillin/clavulanate, nitrofurantoin, isoniazid, trimethoprim-sulfamethoxazole, duloxetine, valproate, interferon-beta, ciprofloxacin, lamotrigine, phenytoin, diclofenac, terbinafine, levofloxacin, aripiprazole | Drug | Rechallenge, Severe positive rechallenge |
Primary outcome
Liver injury rechallenge
Time frame: Up to seven and a half years
Liver injury in relation to rechallenge types (positive, negative, indeterminate and intermediate) for hepatocellular, cholestatic and mixed DILI, respectively, defined according to Danan \& Benichou, 1993, J Clin Epidemiol, 46(11): p. 1323-30.
1 secondary outcome
Severe positive rechallenge
Time frame: Up to seven and a half years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
An observational study of Drug-induced Liver Injury, run by GlaxoSmithKline.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver injury rechallenge (time frame: Up to seven and a half years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2014.