Dose Optimisation of Stavudine for the Treatment of HIV Infection

NCT02670772 | Completed Phase 3 DMC

• 2 other identifiers: WRHI001BMGF
• Study Type: interventional
• Target: 1,077
• Locations: 3 countries
• Sites: 3

Brief Summary

The purpose of this study is to demonstrate whether low dose stavudine (d4T) is non-inferior (in terms of both viral suppression and toxicity) to tenofovir (TDF) after 2 years of HIV treatment.

Conditions

Acquired Immune Deficiency Syndrome; Human Immunodeficiency Virus

Keywords

Antiretroviral Agents

Outcome Measures

Primary Outcomes (2)

• Number of participants with undetectable plasma HIV-1 RNA levels

  Week 48

• Number of participants with adverse events related to treatment

  Week 48

Secondary Outcomes (4)

• Number of patients with plasma HIV-1 RNA levels <200 copies

  Week 96

• Number of participants with abnormal Bone mineral density and fat distribution

  Week 96

• Number of participants with abnormal Bone mineral density.

  Week 96

• Number of participants with abnormal fat distribution

  Week 96

Study Arms (2)

Stavudine

ACTIVE COMPARATOR

Stavudine 20mg twice daily for 96 weeks

Drug: Stavudine

Tenofovir Disoproxil Fumarate

ACTIVE COMPARATOR

Tenofovir 300mg once daily for 96 weeks

Drug: Tenofovir Disoproxil Fumarate

Interventions

Stavudine DRUG

Stavudine 20mg twice daily for 96 weeks + Placebo 300mg once daily for 96 weeks + Lamivudine 150mg twice daily for 96 weeks + Efavirenz 600mg once daily for 96 weeks

Also known as: d4t

Stavudine

Tenofovir Disoproxil Fumarate DRUG

TDF 300mg once daily + Placebo 20mg twice daily for 96 weeks + Lamivudine 150mg twice daily for 96 weeks + Efavirenz 600mg once daily for 96 weeks

Also known as: TDF

Tenofovir Disoproxil Fumarate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is male or female aged ≥18 years (upper limit of \<65 years in India)
• Patient has a documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked immunosorbent assay HIV-1 antibody test) at screening or from previous records
• Patient has a life expectancy of ≥2 years in the opinion of the investigator
• Patient has a plasma HIV-1 RNA level \>1000 copies/mL
• Patient has a plasma CD4 count ≤ 350 cells/mm3 using standard flow cytometry.
• Patient has the following clinical chemistry and haematological laboratory results:
• Serum creatinine ≤1.5 mg/dL (133 μmol/L) and a calculated creatinine clearance level ≥60 mL/min according to the Cockcroft-Gault formula
• Serum alanine aminotransferase \<5 × upper limit of normal (ULN)
• Serum aspartate aminotransferase \<5 × ULN
• Serum lipase ≤1.5 × ULN
• Total bilirubin ≤1.5 mg/dL (25 μmol/L) unless felt by clinician to be due to Gilbert syndrome
• Haemoglobin ≥7.0 g/dLAbsolute neutrophil count ≥500/mm3
• Platelet count ≥50 000/mm3.
• Female patients of childbearing potential, including those who are less than 2 years post-menopausal, must agree to, and comply with using a highly effective method of birth control (eg, barrier contraceptives \[condom or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectable, combination oral contraceptives, transdermal patches, or contraceptive rings\], intrauterine devices, or sexual abstinence) while participating in this study. In addition, all women of childbearing potential must agree to continue to use birth control throughout the study until last study visit Women Not of Childbearing Potential are women who are postmenopausal or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy).
• Women of Childbearing Potential (WOCBP) - Any female who has experienced menarche and does not meet the criteria for "Women Not of Childbearing Potential".

You may not qualify if:

• Patients who have previously received treatment with any form of antiretroviral therapy, including preventing mother-to-child transmission regimens
• Patients who are taking and cannot discontinue the following prohibited concomitant medications at least 1 week prior to the baseline visit and for the duration of the study period:
• Any agents with significant nephrotoxic potential
• Probenecid
• Systemic chemotherapy agents
• Drugs that have significant interactions with EFV other than rifampicin Administration of any of the above medications should be discontinued at least 1 week prior to the baseline visit and for the duration of the study period.
• Patients who have a current history of drug or alcohol abuse that, in the opinion of the investigator, may be an impediment to patient adherence to the protocol
• Patients who have a medical history or evidence of gastrointestinal malabsorption syndrome, chronic nausea, or vomiting which may prevent patients receiving oral medication
• Patients who have participated in a study with an investigational drug within 60 days of screening or who are currently receiving treatment with any other investigational drug or device
• Patients who are hepatitis B surface antigen positive
• Patients with symptomatic peripheral neuropathies
• Female patients who are currently pregnant or breastfeeding
• Female patients desiring pregnancy during the next 2 years
• Patients who have a strong likelihood of relocating far enough to make access to the study site difficult

Sponsors & Collaborators

• Willem Daniel Francois Venter: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (3)

VHS-YRG Care Medical Centre

Chennai, Tamil Nadu, 600113, India

Location

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, 2196, South Africa

Location

The Infectious Disease Institute (IDI), Mulago Hospital Complex

Kampala, Kampala, 25641, Uganda

Location

Related Publications (3)

• Draaijer M, Lalla-Edward ST, Venter WDF, Vos A. Phone Calls to Retain Research Participants and Determinants of Reachability in an African Setting: Observational Study. JMIR Form Res. 2020 Sep 30;4(9):e19138. doi: 10.2196/19138.

  PMID: 32996891 DERIVED

• Venter WDF, Kambugu A, Chersich MF, Becker S, Hill A, Arulappan N, Moorhouse M, Majam M, Akpomiemie G, Sokhela S, Poongulali S, Feldman C, Duncombe C, Ripin DHB, Vos A, Kumarasamy N. Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial. J Acquir Immune Defic Syndr. 2019 Feb 1;80(2):224-233. doi: 10.1097/QAI.0000000000001908.

  PMID: 30640204 DERIVED

• Vos AG, Chersich MF, Klipstein-Grobusch K, Zuithoff P, Moorhouse MA, Lalla-Edward ST, Kambugu A, Kumarasamy N, Grobbee DE, Barth RE, Venter WD. Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir. Retrovirology. 2018 Dec 14;15(1):77. doi: 10.1186/s12977-018-0460-z.

  PMID: 30547820 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Stavudine; Tenofovir

Condition Hierarchy (Ancestors)

HIV Infections; 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Francois Venter, FCP (SA)

  Wits Reproductive Health & HIV Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: February 2, 2016
• Study Start: July 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2015
• Last Updated: February 2, 2016

Record last verified: 2016-01

Locations

ZA (1); UG (1); IN (1)