A 72-week Randomized Clinical Trial Comparing the Safety and Efficacy of Three Initial Antiretroviral Regimens -GPO-VIR S (d4T/3TC/NVP) for 24 Weeks Followed by GPO-VIR Z (AZT/3TC/NVP) vs GPO-VIR Z vs TDF/FTC/NVP - Full Text View

Sponsor:	South East Asia Research Collaboration with Hawaii
Collaborators:	Queen Savang Vadhana Memorial Hospital, Thailand Thai Red Cross AIDS Research Centre University of Hawaii
Information provided by:	South East Asia Research Collaboration with Hawaii
ClinicalTrials.gov Identifier:	NCT00669487

Purpose

This protocol aims to determine the risk/benefits of this policy by comparing head-to-head a regimen of GPO-VIR Z or TDF/FTC/NVP for 18 months in ARV-naïve patients to a 6-month lead in with GPO-VIR S followed by 12 months of GPO-VIR Z. The primary outcomes to be assessed will be anemia, neuropathy, lipoatrophy and renal function.

Condition	Intervention	Phase
HIV Infections	Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Truvada Stavudine

U.S. FDA Resources

Further study details as provided by South East Asia Research Collaboration with Hawaii:

Primary Outcome Measures:

Change from baseline in mean hemoglobin at 24 weeks and 72 weeks [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
Proportion of participants with peripheral neuropathy at 24 weeks and 72 weeks [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Changes from baseline in body weight, limb fat, and lean body mass by DEXA scan at 24 weeks and 72 weeks [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
Change from baseline in serum creatinine at 24 weeks and 72 weeks [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
Proportion of participants with plasma HIV-1 RNA less than 50 copies/mL at 24 weeks and 72 weeks [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
Change from baseline in CD4 count at 24 weeks and 72 weeks [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	April 2008
Study Completion Date:	April 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1. GPO-VIR S 1 pill orally every 12 hours	Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP GPO-VIR S(D4T30mg+3TC150mg+NVP200mg)1 pill orally every 12 hours until week 24 and then switch to GPO-VIR Z Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP GPO-VIR Z(AZT250mg+3TC150mg+NVP200mg) 1 pill orally every 12 hours until week 72
Experimental: 2 GPO-VIR Z 1 pill orally every 12 hours	Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP GPO-VIR S(D4T30mg+3TC150mg+NVP200mg)1 pill orally every 12 hours until week 24 and then switch to GPO-VIR Z Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP GPO-VIR Z(AZT250mg+3TC150mg+NVP200mg) 1 pill orally every 12 hours until week 72
Experimental: 3 Truvada 1 pill oral q 24 hr and NVP 1 pill oral q 12 hr	Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP Truvada(FTC200mg+TDF300mg) every 24 hours + NVP 200 mg every 12 hours orally until week 72 Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP GPO-VIR S(D4T30mg+3TC150mg+NVP200mg)1 pill orally every 12 hours until week 24 and then switch to GPO-VIR Z Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP GPO-VIR Z(AZT250mg+3TC150mg+NVP200mg) 1 pill orally every 12 hours until week 72

Detailed Description:

GPO-VIR Z is a new combination antiretroviral (ARV) medication that substitutes zidovudine (AZT) for stavudine (d4T) from the original formulation of GPO-VIR S. This new combination should decrease rates of lipoatrophy and neuropathy which are side-effects strongly linked to the use of d4T. However, there is some risk that initiating therapy with an AZT- containing regimen may cause unacceptable rates of anemia. Many Thai physicians have adopted a practice of using 6 months of the stavudine-containing GPO-VIR S as a lead in before introducing AZT-containing GPO-VIR Z in an effort to balance the risks and benefits of these two medications. There are no definitive data, however, that can attest to the benefit of such an approach.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Documented HIV-1 infection
Age ≥ 18 years old.
Subjects must be naïve to ARV. Individuals with past exposure to ARV associated with pregnancy will be allowed to enroll as long as the exposure is at least 3 months prior to entry.
CD4 < 350 cells/mm3
Subject understands the study and is able to sign informed consent

Exclusion Criteria:

Evidence of symptomatic persistent symptoms of tingling or numbness of lower extremities and bilateral lower extremity neuropathy on exam at entry. Abnormal exam includes 1) Diminished (compared with the knee) or absent ankle reflexes OR 2) Diminution of either vibration sensation in the legs (defined as perception of vibration for < 10 seconds at the great toe with a tuning fork initially struck hard enough to be audible) OR 3) Diminution of pin or temperature sensation in lower extremities OR 4) Contact allodynia in the feet.
Laboratory values 1) Absolute neutrophil count (ANC) < 750/mm3 2) Hemoglobin < 8.0 g/dL 3) ALT (SGPT) > 5 x ULN 4) Creatinine > 2 X ULN or < creatinine clearance < 30 cc per min by Cockroft-Gault formula
Active AIDS-defining opportunistic infection (OI) within 30 days prior to entry. Subjects must be off all acute treatments for OI for at least 14 days prior to entry. Subjects on maintenance or prophylactic therapy for AIDS-related OIs will be eligible.
Any immunomodulator, HIV vaccine or investigational therapy within 30 days of study entry
Pregnancy or breast-feeding; intent to become pregnant during the course of the study.
Presence of any active malignancy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669487

Locations

Thailand
SEARCH Thailand
Bangkok, Thailand, 10330

Sponsors and Collaborators

South East Asia Research Collaboration with Hawaii

Queen Savang Vadhana Memorial Hospital, Thailand

Thai Red Cross AIDS Research Centre

University of Hawaii

Investigators

Principal Investigator:	Jintanat - Ananworanich, M.D.	SEARCH Thailand
Principal Investigator:	Jintanat - Ananworanich, M.D., Ph.D	SEARCH Thailand

More Information

No publications provided

Responsible Party:	Nitiya Chomchey, SEARCH Thailand
ClinicalTrials.gov Identifier:	NCT00669487 History of Changes
Other Study ID Numbers:	SEARCH003
Study First Received:	April 24, 2008
Last Updated:	May 4, 2011
Health Authority:	Thailand: Food and Drug Administration

Keywords provided by South East Asia Research Collaboration with Hawaii:

HIV/AIDS patients

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Stavudine

Lamivudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 12, 2012