Genotype Based Personalized Prescription of Nevirapine

Study Overview
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Brief Summary
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Genetic tests has been suggested to reduce side effects related to Nevirapine(NVP), a commonly prescribed component of highly active antiretroviral therapy(HAART) in developing countries. This clinical trials is designed to determine the efficacy and the cost-effectiveness of this approach in the developing countries setting. NVP-based HAART and efavirenz(EFV)-based HAART will be provided through Thai national universal health coverage. Information of the prescribed drug will be collected, and monitoring for the compliance with the prescribed highly active antiretroviral therapy will be conducted. Outcome measurements: The primary objective of this study is to evaluate the reduction in incidences of NVP associated cutaneous side effects by genotype based personalized prescription. The volunteers will be monitored for any solicited and non-solicited adverse effects for 6 months after drug administration, with first 6 weeks intensive monitoring for cutaneous adverse reactions. Laboratory safety profiles (Complete Blood Count(CBC), Alanine transaminase(ALT), Aspartate transaminase(AST), Blood Urea Nitrogen(BUN), creatinine, direct bilirubin, total bilirubin, lactate dehydrogenase, alkaline phosphatase) will be assessed during the intensive monitoring period (6 weeks). Statistical Methods: Descriptive statistics will be used to evaluate the conduct of the study. Analysis variables will include overall follow-up rate, drug compliance, and events of protocol violation. Laboratory and safety data will be presented using comparative statistics for each study group and compared within and between groups using standard parametric or non-parametric comparison tests, i.e., McNemar's test or paired t-test as appropriate. Comparison of rate of cutaneous adverse reaction, hepatitis and severe cutaneous adverse reaction(SCAR) will be made with chi-square test. Variable that shown significant different between the standard of care or control group and the genetic test or intervention group will adjusted for the final analysis with Poisson logistic regression. The overall rate of adverse events in all participants will be monitored whether the rate of adverse events is lower than the predefined criteria. The extension of trial may be considered based on the rate of adverse events.

Official Title
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A Multi-center, Double-blinded Randomized Trial for Genotype Based Personalized Prescription of Nevirapine

Conditions
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Nevirapine Induced Rash, Nevirapine Induced Hepatitis, HIV, Adverse Side Effects, AIDS, HIV Infections

Intervention / Treatment
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* Genetic: Genetic test for NVP induced rash
* Other: 3TC/D4T/NVP or 3TC/AZT/NVP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female (non-lactating and non-pregnant), aged between 18-70 years Written informed consent given after reading the volunteer information leaflet. Participation will be voluntary and volunteers will be fully informed of possible side effects. They will be advised that they are free to withdraw at any time. Has confirmed human immunodeficiency virus type 1 infection. Require antiretroviral based on standard practice guideline in Thailand. Adequate venous access Naïve to antiretroviral therapy standard clinical guideline in Thailand. Give consent to determine the genotype status Exclusion Criteria: Women who are breast-feeding Participation in a study of any investigational drug where the study drug was received within the last 30 days Patients who received post or pre-exposure prophylaxis or single dose peripartum prevention incorporated of NVP will be excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care<br>AIDS patients taking care with standard of care | Other: 3TC/D4T/NVP or 3TC/AZT/NVP<br>* Standard HAART for AIDS patients in Thailand<br>|
| Experimental: Genetic test<br>AIDS patients who required highly active antiretroviral therapy(HAART) whom genotype status will be determined before initiation of HAART | Genetic: Genetic test for NVP induced rash<br>* The genotype statuses that capable of predict the cutaneous side effects from nevirapine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the incidences of nevirapine associated rashes in patients who are initiated nevirapine guided by genetic tests (genetic test group) and patients who are initiated nevirapine using standard of care approach (control group). |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the cost-effectiveness of genotyped based personalized prescription of nevirapine. |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Nevirapine induced rash, Hepatitis, Pharmacogenomics, AIDS, treatment naive