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 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:

MedlinePlus related topics: 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:

Compared to the d4T switch and TDF arms, AZT will have a lower Hgb [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
At baseline, the rates of peripheral neuropathy (presumably HIV-induced) will be comparable among the 3 arms [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The overall toxicity profile, as assessed by NIAID Division of AIDS Toxicity Grading Scale, will be less in the AZT and TDF arms compared to the d4T arm [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
All arms will have similar virologic/immunologic outcomes and adherence. [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]

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

Arms	Assigned Interventions
1. GPO-VIR S 1 pill orally every 12 hours: Experimental	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
2 GPO-VIR Z 1 pill orally every 12 hours: Experimental	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
3 Truvada 1 pill oral q 24 hr and NVP 1 pill oral q 12 hr: Experimental	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

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:	SEARCH Thailand ( Nitiya Chomchey )
Study ID Numbers:	SEARCH003
Study First Received:	April 24, 2008
Last Updated:	December 4, 2009
ClinicalTrials.gov Identifier:	NCT00669487 History of Changes
Health Authority:	Thailand: Food and Drug Administration

Keywords provided by South East Asia Research Collaboration with Hawaii:

HIV/AIDS patients

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Stavudine
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Lamivudine
Enzyme Inhibitors

Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on March 18, 2010