Genotype Based Personalized Prescription of Nevirapine

NCT00986063 | Completed Phase 4 DMC

• 1 other identifier: GENPART
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 1

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.

Conditions

Nevirapine Induced Rash; Nevirapine Induced Hepatitis; HIV; Adverse Side Effects; AIDS; HIV Infections

Keywords

Nevirapine induced rash; Hepatitis; Pharmacogenomics; AIDS; HIV; treatment naive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• To determine the cost-effectiveness of genotyped based personalized prescription of nevirapine.

  6 months

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

AIDS patients taking care with standard of care

Other: 3TC/D4T/NVP or 3TC/AZT/NVP

Genetic test

EXPERIMENTAL

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

Interventions

Genetic test for NVP induced rash GENETIC

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

Genetic test

3TC/D4T/NVP or 3TC/AZT/NVP OTHER

Standard HAART for AIDS patients in Thailand

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Surakameth Mahasirimongkol: lead
• Mahidol University: collaborator
• Chulalongkorn University: collaborator
• Thammasat University: collaborator
• Srinakharinwirot University: collaborator
• National Institutes of Health (NIH): collaborator
• RIKEN: collaborator

Study Sites (1)

Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, Bangkok, 10400, Thailand

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections; Hepatitis

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Somnuek Sungkanuparph, MD

  Infectious disease Unit, Department of Internal Mediciine, Faculty of Ramathibodi Medical School, Mahidol University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: September 27, 2009
• First Posted: September 29, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 22, 2013

Record last verified: 2013-04

Locations

TH (1)