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

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

ChemIDplus related topics:

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

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.)

Secondary Outcome Measures:

Rate of decline of RVLA levels
Absolute level of change of RVLA levels using baseline values as a covariant
Proportion of patients improving/normalizing exercise testing mitochondrial dysfunction pattern
Time to event: time to normalize venous lactic acid
Time to event: premature therapy discontinuation, viral load rebound, and progression to a new AIDS defining illness or death
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
Change in absolute CD4 from baseline
Absolute CD4/CD8 counts
Incidence of grade III and greater adverse drug effects
Metabolic laboratory assessments (anion gap, lipid and hepatic profile, and hematology)

Estimated Enrollment:	80
Study Start Date:	August 2001

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

Contacts


Contact: Sophie Geeraerts	604-806-8758	sophie@hivnet.ubc.ca

Locations


Canada, British Columbia
	St. Paul's Hospital	Recruiting
	Vancouver, British Columbia, Canada, V6Z 1Y6
	Contact: Sophie Geeraerts 604-806-8758 sophie@hivnet.ubc.ca
	Contact: Marianne Harris, MD, CCFP 604-806-8771
	Sub-Investigator: Greg Bondy, MD
	Principal Investigator: Dr. Julio Montaner

Canada, Ontario
	Positive Care Clinic	Recruiting
	Toronto, Ontario, Canada
	Contact: Michael Silverman, MD 905-668-6831 ext 3127
	Principal Investigator: Michael Silverman, MD

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

Study ID Numbers:	P00-0159, CTN 169
First Received:	August 31, 2005
Last Updated:	August 3, 2007
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 September 04, 2008

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