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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00310843




Registration number
NCT00310843
Ethics application status
Date submitted
28/03/2006
Date registered
5/04/2006
Date last updated
1/08/2013

Titles & IDs
Public title
Case-Control Viramune (Nevirapine) Toxicogenomics Study
Scientific title
A Case-Control Toxicogenomics Study to Identify Unique Genetic Polymorphisms in Patients Who Have Experienced Symptomatic Hepatotoxicity or Severe Cutaneous Toxicity Within the First 8 Weeks of Nevirapine Therapy
Secondary ID [1] 0 0
2005-004321-26
Secondary ID [2] 0 0
1100.1452
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Treatment: Drugs - Nevirapine

All study population -


Treatment: Drugs: Nevirapine
Patients with HIV-1 infection who have taken or are currently taking nevirapine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Endpoints: relationship between nevirapine-related AEs and genetic polymorphisms loci: Drug metabolizing enzymes (e.g., cytochrome P450 isoforms) Drug transporters (e.g., MDR1 and OATP-C) Human Major Histocompatibility Complex region genes
Timepoint [1] 0 0
Secondary outcome [1] 0 0
Descriptive demographics comparing cases with matched controls in an attempt to link genetic polymorphisms associated with symptomatic hepatotoxicity or severe cutaneous toxicity (cases) to gender, race or other patient characteristics.
Timepoint [1] 0 0

Eligibility
Key inclusion criteria
Inclusion for Case

1. Male or female patients >=18 years of age with HIV-1 infection who experienced one or more of the following adverse reactions within the first 8 weeks of starting nevirapine therapy:

* Grade 3 or 4 LFT elevation (ALT or AST > 5X ULN) and any symptom consistent with clinical hepatitis (see Appendix 10.1)
* Acute liver failure secondary to nevirapine therapy*
* Functional group III or IV rash
* *Acute liver failure is defined as serious liver injury usually requiring hospitalization that may lead to death or liver transplantation.

Inclusion for Control
2. Male or female patients >=18 years of age with HIV-1 infection who have been exposed to nevirapine therapy for at least 18 weeks and who do not meet any of the case inclusion criteria
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion for Cases

1. Patients with any hepatotoxicity or rash event which in the investigators judgement is not related to nevirapine use (ex. hepatotoxicity due to alcohol or other medicinal use or rash due to other medicinal use).
2. Patients who began abacavir or TMP-SMX (trimethoprim/sulfamethoxazole) therapy 2 weeks or less prior to or up to 8 weeks after initiating nevirapine therapy.
3. Patients with AST or ALT elevations > 5 times the ULN (>= Grade 3) just prior to the initiation of nevirapine therapy.

Exclusion for Controls
4. Patients who discontinued nevirapine before completing 18 weeks of dosing with 200 mg/day for 2 weeks followed by 400 mg/day thereafter.
5. Patients who developed functional group I, IIa or IIb rash within 18 weeks of starting nevirapine therapy, or any dermatologic condition that could plausibly be attributed to nevirapine.
6. Patients with ALT or AST elevations >2.5 X ULN (>Grade 1) within 18 weeks of starting nevirapine therapy.
7. Any hepatobiliary adverse event that could possibly be attributed to nevirapine.
8. Patients who develop any systemic reaction attributable to nevirapine use during the first 18 weeks of nevirapine treatment such as flu-like symptoms, arthralgia, myalgia, or conjunctivitis.

Exclusion for Cases and Controls
9. Patients who have participated in the 2NN-Long-term Follow-up study (1100.1454)
10. Patients with CD4 count 150 cells/mm3 prior to the initiation of nevirapine therapy (last available result measured 6 months prior to the initiation of nevirapine therapy).
11. Evidence of acute co-infection with viral hepatitis.
12. Patients taking prednisone, prednisolone, or immuno-modulatory medication within the first 8 weeks of nevirapine therapy.
13. Patients who are unwilling to provide blood samples for DNA testing.
14. Patients who did not sign informed consent and or authorization to release protected health information per local requirements.
15. Patients without available liv

Study design
Purpose
Duration
Selection
Timing
Retrospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
889
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
1100.1452.61004 Boehringer Ingelheim Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
1100.1452.61005 Boehringer Ingelheim Investigational Site - DarlingHurst
Recruitment hospital [3] 0 0
1100.1452.61006 Boehringer Ingelheim Investigational Site - Darlinghurst
Recruitment hospital [4] 0 0
1100.1452.61003 Boehringer Ingelheim Investigational Site - Miami
Recruitment hospital [5] 0 0
1100.1452.61002 Boehringer Ingelheim Investigational Site - Carlton
Recruitment hospital [6] 0 0
1100.1452.61008 Boehringer Ingelheim Investigational Site - Melbourne
Recruitment hospital [7] 0 0
1100.1452.61001 Boehringer Ingelheim Investigational Site - South Yarra
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- DarlingHurst
Recruitment postcode(s) [3] 0 0
- Miami
Recruitment postcode(s) [4] 0 0
- Carlton
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment postcode(s) [6] 0 0
- South Yarra
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Colorado
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United States of America
State/province [3] 0 0
Connecticut
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
State/province [6] 0 0
Missouri
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Argentina
State/province [11] 0 0
Capital Federal
Country [12] 0 0
Argentina
State/province [12] 0 0
Rosario
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Canada
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British Columbia
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Canada
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Ontario
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France
State/province [15] 0 0
Bordeaux
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France
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Lyon cedex 2
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France
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Lyon Cedex 3
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France
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Lyon cedex 3
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France
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Lyon
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France
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Nantes cedex 1
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France
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Nantes
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France
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Paris cedex 12
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France
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Paris cedex 20
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France
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Paris
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France
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Toulouse cedex 9
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France
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Toulouse
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France
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Tourcoing cedex
Country [28] 0 0
France
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Vandoeuvre les Nancy
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Bochum
Country [31] 0 0
Germany
State/province [31] 0 0
Bonn
Country [32] 0 0
Germany
State/province [32] 0 0
Düsseldorf
Country [33] 0 0
Germany
State/province [33] 0 0
Essen
Country [34] 0 0
Germany
State/province [34] 0 0
Frankfurt am Main
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
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Germany
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München
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Germany
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Ulm
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Germany
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Würzburg
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Netherlands
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Amsterdam
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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L'Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Sevilla
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Khon Kaen
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United Kingdom
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Birmingham
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United Kingdom
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Brighton
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United Kingdom
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Coventry
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United Kingdom
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London
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United Kingdom
State/province [54] 0 0
Manchester
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Plaistow, London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Attempt to identify genetic polymorphisms in interrogated pathways which may be associated with symptomatic hepatotoxicity or severe cutaneous toxicity observed in case patients within the first 8 weeks of nevirapine therapy.
Trial website
https://clinicaltrials.gov/study/NCT00310843
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00310843