Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
GS-ES-164-0154
Study information
Scientific title
Pilot phase IV, multicenter, randomized, open-label and controlled study to assess the evolution of peripheral body fat distribution after switching from zidovudine-containing backbone to truvada in HIV-1-infected patients on highly active antiretroviral therapy
Acronym
RECOMB
Study hypothesis
Eligible patients must have been on zidovudine (AZT) treatment for at least six months. The rational for this criterion is that it has been widely described that after this period of time, sub-clinical body fat changes can be developed, related to alterations in mitochondrial function and replication capacity of the subcutaneous adipose tissue. These changes could lead to an objective lipoatrophy (loss of 20% of peripheral fat) several months later. To assess the potential benefit of switching to truvada is the main objective for this study. Another objective of this study is to evaluate the changes in body fat distribution as measured by dual-energy x-ray absortiometry (DEXA) after switching from AZT-containing backbone to truvada
Ethics approval
Ethics Committee of the Hospital Vall d'Hebron, Barcelona, Spain, 10/03/2006
Study design
Pilot phase IV multicenter open-labelled randomized controlled study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Human immunodeficiency virus (HIV)
Intervention
Patients on current HAART regimen containing zidovudine and lamivudine at usual doses for at least six months, will be randomised to switch to truvada (fixed-dose combination of tenofovir and emtricitabine) or to continue with the same HAART regimen containing zidovudine and lamividine. The other drugs included in the original HAART regimen will not change.
Intervention type
Drug
Phase
Phase IV
Drug names
Zidovudine, lamivudine, truvada (fixed-dose combination of tenofovir and emtricitabine)
Primary outcome measures
Objective assessment of change from baseline in limb fat at week 48 as measured by DEXA
1. Dual-energy x-ray absortiometry (DEXA) scans will be performed at baseline, week 24, week 48 and week 72
2. Study of mitochondrial toxicity at baseline, week 12, week 24, week 48 and week 72
Secondary outcome measures
1. Change in the mitochondrial deoxyribonucleic acid (DNA) or nuclear DNA ratio in the different visits compared with baseline
2. Change in lactate concentration in the different visits compared with baseline
3. Proportion of patients who maintain confirmed HIV-1 RNA levels of <50 copies per ml
4. Proportion of patients with HIV-1 RNA levels between >50 and <400 copies per ml
5. Proportion of patients with virologic failure as confirmed by two consecutive HIV-1 RNA >400 copies/ml
6. Time to loss of virological response, defined as the time elapsed from the patient’s first dose of study drug to confirmed HIV-1 RNA levels of >50 and <400 copies/ml, death caused by the disease, medication discontinuation, or addition of a new antiretroviral medication
7. Time to definite virological failure, defined as the time elapsed from the patient’s first dose of study drug to confirmed HIV-1 RNA levels of >400 copies/ml
8. Change in CD4+ cell counts in the different study visits compared with baseline
9. Change in serum triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) fractions in the different study visits compared with baseline
10. Change in hemoglobin and hematocrit concentrations in the different visits compared with baseline
11. Proportion of patients with different specific mutations after virological failure
12. Proportion of patients who show treatment adherence
Overall trial start date
05/04/2006
Overall trial end date
12/12/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. Human immunodeficiency virus (HIV-1) infection as documented by positively confirmed HIV-1 antibody test and/or positive polymerase chain reaction (PCR) for HIV-1 ribonucleic acid (RNA)
2. Adult patients (over 18 years of age)
3. Currently on highly active antiretroviral therapy (HAART) regimen, containing zidovudine and lamivudine at usual doses for at least six months
4. Viral load <50 copies/ml on the last two consecutive determinations under zidovudine and lamivudine-containing HAART regimen
5. For women of childbearing potential, negative urine pregnancy test at screening visit
6. Agreement to take part in the study and signed informed consent form
7. Patients on lipid-lowering treatment will be allowed to participate in the study only if the lipid-lowering treatment (either statins or fibrates) is stable for at least eight weeks prior to screening and is not expected to change this treatment during the first three months of the trial
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
80
Participant exclusion criteria
1. Patients on current transdermal fentanyl (TDF) or emtricitabine (FTC) therapy
2. Patients with a previous history of virological failure on FTC or TDF-containing regimen
3. Patients receiving a non-registered antiretroviral (ARV) drug
4. Patients receiving a triple nucleoside-ARV combination
5. Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of these drugs
6. Known history of drug abuse or chronic alcohol consumption
7. Women who are pregnant or breast-feeding or females of childbearing potential who do not use an adequate method of contraception according to the investigator’s judgment
8. Current active opportunistic infection or documented infection within the previous four weeks
9. Documented active malignant disease (excluding Kaposi’s sarcoma limited to the skin)
10. Renal disease with creatinine clearance <50 ml/min
11. Concomitant use of nephrotoxic or immuno-suppressive drugs, which cannot be stopped without affecting the safety of the patient
12. Receiving on-going therapy with systemic corticosteroids, interleukin-2 (IL-2) or chemotherapy
13. Patients not to be included in the study according to the investigator’s criterion
Recruitment start date
05/04/2006
Recruitment end date
12/12/2007
Locations
Countries of recruitment
Spain
Trial participating centre
Hospital Vall d'Hebrón
Barcelona
08035
Spain
Sponsor information
Organisation
Gilead Sciences, SL (Spain)
Sponsor details
C/ Vía de los Poblados
3
Edificio 7/8
planta 6ª
Madrid
28033
Spain
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Gilead Sciences, SL
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary