D4T or Abacavir Plus Vitamin Enhancement in HIV-Infected Patients (DAVE) - Full Text View

Sponsors and Collaborators:	University of British Columbia GlaxoSmithKline Canadian HIV Trials Network
Information provided by:	University of British Columbia
ClinicalTrials.gov Identifier:	NCT00143702

Purpose

The purpose of this study is to determine the best way to treat people on d4T (stavudine) with high levels of lactic acid. Switching from d4T to abacavir will be assessed. Adding riboflavin and thiamine will also be assessed.

Participants will be randomly assigned to one of four groups:

Group 1 participants will continue to take d4T as part of their antiretroviral (ARV) regimen, and will be given the vitamin supplements
Group 2 will continue to take d4T without vitamin supplements
Group 3 will switch from d4T to abacavir and receive the vitamins
Group 4 will switch from d4T to abacavir without vitamin supplements.

The study plans to involve eighty participants from Canada and Argentina for a treatment period of 16 weeks and a follow-up visit at week 24.

Condition	Intervention	Phase
Acidosis, Lactic	Drug: d4T Drug: Abacavir Drug: Riboflavin and Thiamine (Supplementation)	Phase II Phase III

MedlinePlus related topics: AIDS

Drug Information available for: Abacavir Abacavir sulfate Stavudine Lactic acid Ammonium lactate Riboflavin Thiamine 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2-hydroxyethyl)-4-m- ethylthiazolium chloride, monohydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment
Official Title:	Randomized, Open-Label Study of Continued Stavudine Versus Abacavir Substitution With or Without Riboflavin and Thiamine Supplementation in HIV-Infected Patients Who Have Elevated Venous Lactic Acid While on Stavudine-Based Therapy (DAVE)

Further study details as provided by University of British Columbia:

Primary Outcome Measures:

Proportion of patients per arm with random venous lactic acid (RVLA) below or equal to 2.1 mmol/L* at 16 weeks. (* Confirmed by a second determination 7-14 days later.) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of decline of RVLA levels [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Absolute level of change of RVLA levels using baseline values as a covariant [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Proportion of patients improving/normalizing exercise testing mitochondrial dysfunction pattern [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Time to event: time to normalize venous lactic acid [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Time to event: premature therapy discontinuation, viral load rebound, and progression to a new AIDS defining illness or death [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Proportion of patients with at least three consecutive HIV-1 RNA determinations equal to or below 50 copies/mL during the 16 week follow-up period on an intention to treat basis [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Change in absolute CD4 from baseline [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Absolute CD4/CD8 counts [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Incidence of grade III and greater adverse drug effects [ Time Frame: Unspecified ] [ Designated as safety issue: No ]
Metabolic laboratory assessments (anion gap, lipid and hepatic profile, and hematology) [ Time Frame: Unspecified ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	August 2001
Study Completion Date:	August 2006
Primary Completion Date:	August 2006 (Final data collection date for primary outcome measure)

Intervention Details:

See Detailed Description.

Eligibility

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

Criteria

Inclusion Criteria:

Be HIV-positive
Be 18 years of age or older
Have a viral load equal to or below 50 copies/mL
Have been on a d4T-containing multiple drug regimen (at least three agents in total) for at least six months
Have been on a stable ARV regimen for the three months prior to enrollment
Have a venous lactic acid measurement above 2.1 mmol/L within the three months prior to enrollment and two consecutive measurements above 2.1 but lower than 6.0 within a two-week period of screening
Be willing to discontinue L-carnitine and/or coenzyme Q10
Be willing and able to provide informed consent

Exclusion Criteria:

Pregnancy or breastfeeding
Venous lactic acid equal to or above 6.0 mmol/L
Previous exposure to abacavir
Virologic rebound while on a previous regimen consisting of dual or triple nucleoside reverse transcriptase inhibitors (NRTIs)
Use of hydroxyurea within the three months prior to enrollment
Use of metformin
Any acute cardiopulmonary illness or infection
New AIDS-defining illness diagnosed within four weeks of enrollment
Riboflavin or thiamine supplementation above 20 mg/day within 30 days prior to enrollment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00143702

Locations

Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
Positive Care Clinic
Toronto, Ontario, Canada

Sponsors and Collaborators

University of British Columbia

GlaxoSmithKline

Canadian HIV Trials Network

Investigators

Principal Investigator:

Julio Montaner, MD

University of British Columbia

More Information

Related Info This link exits the ClinicalTrials.gov site

Responsible Party:	University of British Columbia ( Dr. Julio Montaner )
Study ID Numbers:	P00-0159, CTN 169
Study First Received:	August 31, 2005
Last Updated:	September 24, 2008
ClinicalTrials.gov Identifier:	NCT00143702
Health Authority:	Canada: Health Canada

Keywords provided by University of British Columbia:

Elevated Lactic Acid

Study placed in the following topic categories:

Stavudine
Metabolic Diseases
Acidosis, Lactic
Riboflavin
HIV Infections

Acquired Immunodeficiency Syndrome
Thiamine
Abacavir
Metabolic disorder
Acidosis

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-HIV Agents
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Antiviral Agents
Acid-Base Imbalance
Pharmacologic Actions

Reverse Transcriptase Inhibitors
Photosensitizing Agents
Anti-Retroviral Agents
Radiation-Sensitizing Agents
Therapeutic Uses
Vitamins
Micronutrients
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009