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

Acidosis, Lactic Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00143702
• Other study ID #: P00-0159
• Secondary ID: CTN 169
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 31, 2005
• Last updated: September 24, 2008
• Start date: August 2001
• Est. completion date: August 2006

Study information

• Verified date: September 2005
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acidosis, Lactic

Intervention

Drug:
• d4T
See Detailed Description.
• Abacavir
See Detailed Description.
• Riboflavin and Thiamine (Supplementation)
See Detailed Description.

Locations

Country	Name	City	State
Canada	Positive Care Clinic	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (3)

Lead Sponsor	Collaborator
University of British Columbia	CIHR Canadian HIV Trials Network, GlaxoSmithKline

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.)		16 weeks	No
Secondary	Rate of decline of RVLA levels		Unspecified	No
Secondary	Absolute level of change of RVLA levels using baseline values as a covariant		Unspecified	No
Secondary	Proportion of patients improving/normalizing exercise testing mitochondrial dysfunction pattern		Unspecified	No
Secondary	Time to event: time to normalize venous lactic acid		Unspecified	No
Secondary	Time to event: premature therapy discontinuation, viral load rebound, and progression to a new AIDS defining illness or death		Unspecified	No
Secondary	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		16 weeks	No
Secondary	Change in absolute CD4 from baseline		Unspecified	No
Secondary	Absolute CD4/CD8 counts		Unspecified	No
Secondary	Incidence of grade III and greater adverse drug effects		Unspecified	No
Secondary	Metabolic laboratory assessments (anion gap, lipid and hepatic profile, and hematology)		Unspecified	No