Clinical trial NCT00143702: D4T or Abacavir Plus Vitamin Enhancement in HIV-Infected Patients (DAVE)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acidosis, Lactic
Keywords: Elevated Lactic Acid
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: CIHR Canadian HIV Trials Network
First posted: 2005-09-02
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: 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.)
timeFrame: 16 weeks
Secondary outcomes:
measure: Rate of decline of RVLA levels
measure: Absolute level of change of RVLA levels using baseline values as a covariant
measure: Proportion of patients improving/normalizing exercise testing mitochondrial dysfunction pattern
measure: Time to event: time to normalize venous lactic acid
measure: Time to event: premature therapy discontinuation, viral load rebound, and progression to a new AIDS defining illness or death
measure: 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
timeFrame: 16 weeks
measure: Change in absolute CD4 from baseline
measure: Absolute CD4/CD8 counts
measure: Incidence of grade III and greater adverse drug effects
measure: Metabolic laboratory assessments (anion gap, lipid and hepatic profile, and hematology)
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Positive Care Clinic
state: Ontario
Study officials:
affiliation: University of British Columbia
name: Julio Montaner, MD
role: PRINCIPAL_INVESTIGATOR
References: