Clinical trial NCT00323492: TOTEM: Switch From Other Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to Once Daily Truvada
Official title: Open-label Randomized Multicenter Trial to Evaluate the Impact on the Lipid Profile of the Substitution of the NRTIs of a HAART Regimen by a Once Daily Fixed Dose Combination Tablet of Emtricitabine and Tenofovir DF Versus Maintained Treatment in HIV Infected Controlled Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV 1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2006-05-09
Enrollment: 92
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: This study looked at lipid changes in human immunodeficiency virus type 1 (HIV-1) infected patients when the nucleoside reverse transcriptase inhibitors (NRTIs) in their existing highly active antiretroviral therapy (HAART) regimen were switched to Truvada® (a fixed dose combination tablet of emtricitabine/tenofovir disoproxil fumarate 200 mg/300 mg \[FTC/TDF\]). Subjects continued their nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) at the same dose.

Detailed description: This was a Phase IV, multicenter (in France), open label study. The study was conducted in two phases: a comparative randomized phase, which served the primary objective of the study, and a follow-up phase.

Study Phase 1, Day -14 to Week 12: patients were randomized on a 1:1 basis to one of two groups:

* A. Truvada (substitution of their current NRTIs by Truvada \[FTC/TDF\] with continuation of their current NNRTI or PI at the same dose)
* B. Maintain Baseline Regimen (continuation of previous HAART regimen, i.e., maintained baseline regimen).

This phase of the study served the primary objective of the study.

Study Phase 2, roll-over follow-up, Week 12 to Week 48: Patients in the Truvada group continued with Truvada + an NNRTI or PI. Patients in the control group could switch their NRTIs to Truvada in this phase of the study (Delayed Truvada group).

Patients were assessed for efficacy and safety during both phases of the study.

Eligibility criteria: Inclusion Criteria:

* Patients displaying abnormal fasted triglycerides (\> 2 g/L \[2.26 mmol/L\] and less than or equal to 10 g/L \[11.29 mmol/L\]) and/or fasted low density lipoprotein cholesterol (LDL-CHO; \> 1.6 g/L \[4.15 mmol/L\])
* Patients on stable HAART with 2 NRTIs + 1 NNRTI or 1 PI for at least 3 months prior to screening, and with plasma viral load \< 400 copies/mL for at least 6 months prior to screening

Primary outcomes:
measure: Change From Baseline to Week 12 in Fasting Triglycerides
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO)
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO)
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO)
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP)
timeFrame: Baseline to Week 12
measure: Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12
timeFrame: 12 weeks
measure: Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 48 in CD4 Cell Count
timeFrame: Baseline to Week 48
measure: Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12
timeFrame: 12 weeks
measure: Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12
timeFrame: 12 weeks
measure: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Gilead Sciences
Study officials:
affiliation: Gilead Sciences
name: Camille Aubron-Olivier
role: STUDY_DIRECTOR
References:
citation: Valantin MA, Bittar R, de Truchis P, Bollens D, Slama L, Giral P, Bonnefont-Rousselot D, Petour P, Aubron-Olivier C, Costagliola D, Katlama C; TOTEM trial group. Switching the nucleoside reverse transcriptase inhibitor backbone to tenofovir disoproxil fumarate + emtricitabine promptly improves triglycerides and low-density lipoprotein cholesterol in dyslipidaemic patients. J Antimicrob Chemother. 2010 Mar;65(3):556-61. doi: 10.1093/jac/dkp462. Epub 2010 Jan 6.