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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

This study has been completed.
Sponsor:
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
First received: April 24, 2008
Last updated: May 4, 2011
Last verified: July 2009
  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 3

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:


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:

  1. Documented HIV-1 infection
  2. Age ≥ 18 years old.
  3. 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.
  4. CD4 < 350 cells/mm3
  5. Subject understands the study and is able to sign informed consent

Exclusion Criteria:

  1. 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.
  2. 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
  3. 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.
  4. Any immunomodulator, HIV vaccine or investigational therapy within 30 days of study entry
  5. Pregnancy or breast-feeding; intent to become pregnant during the course of the study.
  6. Presence of any active malignancy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Stavudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014