Genotype Based Personalized Prescription of Nevirapine

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

Sponsors

Lead Sponsor: Surakameth Mahasirimongkol

Collaborator: Mahidol University
Chulalongkorn University
Thammasat University
Srinakharinwirot University
National Institutes of Health (NIH)
RIKEN

Source Mahidol University
Brief Summary

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.

Overall Status Completed
Start Date July 2009
Completion Date December 2012
Primary Completion Date July 2012
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure 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
Measure Time Frame
To determine the cost-effectiveness of genotyped based personalized prescription of nevirapine. 6 months
Enrollment 1200
Condition
Intervention

Intervention Type: Genetic

Intervention Name: Genetic test for NVP induced rash

Description: The genotype statuses that capable of predict the cutaneous side effects from nevirapine

Arm Group Label: Genetic test

Intervention Type: Other

Intervention Name: 3TC/D4T/NVP or 3TC/AZT/NVP

Description: Standard HAART for AIDS patients in Thailand

Arm Group Label: Standard of care

Eligibility

Criteria:

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Somnuek Sungkanuparph, MD Principal Investigator Infectious disease Unit, Department of Internal Mediciine, Faculty of Ramathibodi Medical School, Mahidol University
Location
Facility: Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University
Location Countries

Thailand

Verification Date

April 2013

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Mahidol University

Investigator Full Name: Surakameth Mahasirimongkol

Investigator Title: Dr.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Standard of care

Type: Active Comparator

Description: AIDS patients taking care with standard of care

Label: Genetic test

Type: Experimental

Description: AIDS patients who required highly active antiretroviral therapy(HAART) whom genotype status will be determined before initiation of HAART

Acronym GENPART
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov