Differences Between Stavudine and Tenofovir Each Combined With Lamivudine and Efavirenz in SA HIV-infected Patients

NCT01601899 | Terminated Phase 4 DMC

• 1 other identifier: CHRU01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Even with the benefits of HIV therapy, there is a possibility that HIV-infected individuals develop metabolic complications once they initiate treatment, which may also ultimately put them at a risk for impending heart disease in the next decades. The main mechanism through which the main HIV drugs are thought to cause these metabolic changes and organ toxicities is mitochondrial toxicity. Most of studies that have been done, have taken place in the West, but few, if any, have been done in South Africa. The purpose of this study is to prospectively identify early changes between the two different drugs, Stavudine and Tenofovir, to assess their virological response, molecular, biochemical and clinical picture, and the possible associated change in cardiovascular risk factors, this, in the South African setting, and make recommendations to modify the current National AIDS role out programme

Conditions

Mitochondrial Toxicity; Metabolic Complications

Keywords

trial; stavudine; tenofovir; mitochondria; insulin resistance; lipids; HOMA

Outcome Measures

Primary Outcomes (8)

• changes in mitochondrial DNA copy number in adipocyte tissue

  from baseline to 4 weeks

• changes in gene expression in adipocyte tissue

  from baseline to 4 weeks

• changes in lipid levels

  from baseline to 4 weeks

• changes in glycaemic indices

  from baseline to 4 weeks

• changes in adipocytokines

  from baseline to 4 weeks

• changes in lipid levels

  from baseline to 48 weeks

• changes in glycaemic indices

  from baseline to 48 weeks

• changes in adipocytokines

  from baseline to 48 weeks

Secondary Outcomes (6)

• Time from randomization to virologic failure

  up to 48 weeks

• Time from randomization to death

  up to 48 weeks

• time from randomization to the first adverse event requiring discontinuation of any of the drugs that formed the initial regimen

  up to 48 weeks

• time from randomization to the first Grade 3 or higher adverse event.

  up to 48 weeks

• Time from randomization to HIV-related disease progression (defined as progression to WHO Clinical Stage 3 or 4)

  up to 48 weeks

Study Arms (3)

ARM A

ACTIVE COMPARATOR

Stavudine (d4T) 30 mg po BD if wt \< 60kg, or 40 mg po BD if wt \> 60kg PLUS Lamivudine (3TC) 150mg po BD PLUS Efavirenz 600mg po nocte

Drug: Stavudine

ARM B

ACTIVE COMPARATOR

Stavudine (d4T) 20 mg po BD if wt \< 60kg, or 30 mg po BD if wt \> 60kg PLUS Lamivudine (3TC) 150mg po BD PLUS Efavirenz 600mg po nocte

Drug: Stavudine

ARM C

ACTIVE COMPARATOR

TDF 300 mg po QD PLUS Lamivudine (3TC) 150mg po BD PLUS Efavirenz 600mg po nocte

Drug: Tenofovir

Interventions

Stavudine DRUG

30 mg po BD if wt \< 60kg, or 40 mg po BD if wt \> 60kg

Also known as: Lamivudine (3TC) 150mg po BD, PLUS, Efavirenz 600mg po nocte

ARM A

Tenofovir DRUG

300 mg po QD

Also known as: PLUS, Lamivudine (3TC) 150mg po BD, Efavirenz 600mg po nocte

ARM C

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection, documented by a rapid HIV test or any licensed ELISA test kit, and confirmed by either a second rapid HIV test or an ELISA consistent with the Themba Lethu Clinic guidelines.
• Age \>/= 18 years,
• CD4+ cell count \< 200 cells/mm3.
• The following laboratory values obtained within 45 days prior to study entry:
• Absolute neutrophil count (ANC) ≥ 750/mm3
• Hemoglobin ≥ 7.0 g/dL
• Platelet count ≥ 50,000/mm3
• AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN
• Total bilirubin ≤ 2.5 x ULN
• Evidence of normal renal function within 45 days prior to study entry as determined by an estimated creatinine clearance of ≥60 mL/min using the Cockcroft-Gault formula:
• {\[140 - age (yr)\] x \[weight (kg)\] ÷ \[72 x serum Cr (mg/dL)\]} (X 0.85 in females.)
• Participants of reproductive age (defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e. who have had menses within the preceding 24 months), or who have not undergone surgical sterilization (e.g. hysterectomy, or bilateral oophorectomy or salpingotomy) must have a negative serum or urine pregnancy test within 45 days prior to study entry.
• Participants of reproductive potential, must be willing to abstain from participation in a conception process (e.g. active attempt to become pregnant or in vitro fertilization). If participants are sexual active, that could lead to pregnancy, they must use at least one reliable form of contraception listed below while receiving protocol-specified medications and for 6 weeks after stopping the medication.
• Male or female condoms with or without a spermicidal agent (condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission).
• Diaphragm or cervical cap with spermicide

You may not qualify if:

• Receipt of any antiretrovirals (including for purposes of occupational or sexual post exposure prophylaxis), except for SD Nevirapine taken within six months.
• Use of systemic cancer chemotherapy, systemic investigational agents, immunomodulators (growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons) or rifampin within 30 days prior to study entry.
• Breastfeeding or pregnancy.
• Allergy to study drugs.
• Any condition, including active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Any serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry.
• Involuntary incarceration in a correctional facility, for legal reasons or in a medical facility for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead

Study Sites (1)

Themba Lethu Clinic, Helen Joseph Hospital, Auckland Park

Johannesburg, Gauteng, 2006, South Africa

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Stavudine; Lamivudine; efavirenz; Tenofovir

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Colin N Menezes, FCP(SA)

  Clinical HIV Research Unit, University of the Witwatersrand

  PRINCIPAL INVESTIGATOR

• Ian Sanne, FCP(SA)

  Clinical HIV Research Unit, University of the Witwatersrand

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Infectious Diseases Physician and Lecturer

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: May 18, 2012
• Study Start: October 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 18, 2012

Record last verified: 2012-05

Locations

ZA (1)