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

ISRCTN	ISRCTN81993634
DOI	https://doi.org/10.1186/ISRCTN81993634
Protocol serial number	GS-ES-164-0154
Sponsor	Gilead Sciences, SL (Spain)
Funder	Gilead Sciences, SL

Submission date: 23/01/2006
Registration date: 11/04/2006
Last edited: 13/07/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Esteban Ribera Pascuet
Scientific

Hospital Vall d'Hebrón
Passeig de Vall D'Hebrón, 119-129
Barcelona
08035
Spain

Study information

Primary study design	Interventional
Study design	Pilot phase IV multicenter open-labelled randomized controlled study
Secondary study design	Randomised controlled trial
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
Study acronym	RECOMB
Study objectives	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(s)	Ethics Committee of the Hospital Vall d'Hebron, Barcelona, Spain, 10/03/2006
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Zidovudine, lamivudine, truvada (fixed-dose combination of tenofovir and emtricitabine)
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	12/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	80
Key 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
Key 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
Date of first enrolment	05/04/2006
Date of final enrolment	12/12/2007

Locations

Countries of recruitment

Spain

Study participating centre

Hospital Vall d'Hebrón

Barcelona
08035
Spain

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan