HIV-1Phase 4RECOMBNCT00324649
Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada
A Phase 4 study testing Truvada and Zidovudine/lamivudine in people with HIV-1, run by Gilead Sciences at 1 site in Spain.
Trial summary
This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1
- What is being tested?
- Truvada and Zidovudine/lamivudine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteSpain
- Study dates
- May 2006to Sep 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive polymerase chain reaction for HIV-1 ribonucleic acid (RNA).
- Adult patients (over 18 years of age).
- Current HAART regimen containing zidovudine + lamivudine at usual doses for at least 6 months.
- Viral load < 50 copies/mL on the last two consecutive determinations, under zidovudine + lamivudine containing HAART regimen.
- For women of childbearing potential, negative urine pregnancy test at screening visit.
- Agreement to take part in the study and sign the informed consent.
- Patients on lipid lowering treatment were allowed to participate in the study only if the lipid-lowering treatment (either statins or fibrates) was stable for at least 8 weeks prior to screening and it was not expected to change during the first 3 months of the study.
Who cannot join
- Patients on current FTC or TDF therapy.
- Patients with previous history of virological failure on an FTC or TDF-containing regimen.
- Patients receiving a non-registered antiretroviral drug.
- Patients receiving a triple-nucleoside antiretroviral combination.
- Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of those drugs.
- Known history of drug abuse or chronic alcohol consumption
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- Women who were pregnant or breast feeding, or female of childbearing potential who did not use an adequate method of contraception according to the investigator's judgment.
- Active opportunistic infection or documented infection within the previous 4 weeks.
- Documented active malignant disease (excluding Kaposi sarcoma limited to the skin).
- Renal disease with creatinine clearance < 50 mL/min.
- Concomitant use of nephrotoxic or immuno-suppressive drugs which could not be stopped without affecting the safety of the patient.
- Receiving on-going therapy with systemic corticosteroids, Interleukin-2 or chemotherapy.
- Patients who were not to be included in the study according to the investigator's criterion.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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 HAART (RECOMB Study).
This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine [FTC, 200 mg] and tenofovir disoproxil fumarate [TDF, 300 mg]) or who remained on a zidovudine- plus lamivudine-containing regimen. Subjects continued their protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).
Read the detailed description
Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (PI or NRTI).
The use of nucleoside analogues, especially stavudine and zidovudine, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances.
As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the European Medicines Agency (EMA) in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection".
In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing zidovudine and lamivudine were randomized to switch to Truvada or to stay on their zidovudine- plus lamivudine-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).
- Conditions
- HIV-1
- Being tested
- Truvada, Zidovudine/lamivudine
- Keywords
- HIV-1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TruvadaDrug
Truvada once daily with continuation of the current NNRTI or PI at randomization.
Zidovudine/lamivudineDrug
Continuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization.
| Study group | Role | What they receive |
|---|---|---|
| Truvada | Experimental | Truvada + NNRTI or PI. Receives: Drug: Truvada |
| Zidovudine/lamivudine | Active comparator | Zidovudine/lamivudine + NNRTI or PI. Receives: Drug: Zidovudine/lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Limb Fat at Week 48
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Secondary outcomes (17)
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa)
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes)
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in Lactate Concentration
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Percentage of Days for Which Participants Were Compliant With Study Drug
Compliance = [1 - [(sum of days with a missed dose [per Question 6 study medication assessment questionnaire (SMAQ)])/(sum of days between SMAQ visits)]] *100 for visits with SMAQ data. An assessable visit is one where the number of missed days was reported [Question 6] and the number of days between SMAQ visits could be calculated.
Measured: Baseline to Week 72
Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL
Measured: 48 weeks
Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL
Measured: 48 weeks
Percentage of Participants With Virologic Failure
Virologic failure was defined as two consecutive HIV RNA values > 400 copies/mL.
Measured: 48 weeks
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in Fasting Serum Triglycerides
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in Fasting Total Cholesterol
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL)
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL)
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Change From Baseline in Hemoglobin
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Percent Change From Baseline in Hematocrit
Change = Week 48 value minus baseline value expressed as median percent change.
Measured: Baseline to Week 48
Change From Baseline in Waist Circumference/Hip Circumference Ratio
Change = Week 48 value minus baseline value.
Measured: Baseline to Week 48
Percentage of Participants With Any Adverse Event
Participants with treatment-emergent adverse events were analyzed. Adverse events were defined as any untoward medical occurrence in a clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with study treatment, and were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Version 11.
Treatment-emergent adverse events were events that met one of the following criteria:
- Began or worsened in severity or relationship to study drug, on or after the date of the first dose of study drug and on or before the date of the last dose of study drug plus 30 days.
- Had no recorded start date.
Measured: 72 weeks
Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startMay 2006
- Primary completionMar 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV-1Studies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pedro Ferrer, Study director, Gilead Sciences, S.L.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00324649
- Sponsor's protocol ID
- GS-ES-164-0154
- Acronym
- RECOMB
- Status last verified
- Aug 2015
- First submitted
- 9 May 2006
- Last updated
- 17 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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 HAART (RECOMB Study).
- ClinicalTrials.gov ID
- NCT00324649
- Acronym / sponsor ID
- RECOMB / GS-ES-164-0154
- Conditions
- HIV-1
- Keywords
- HIV-1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Mar 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 11 May 2006 (estimated)
- Results
- Posted 20 May 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine [FTC, 200 mg] and tenofovir disoproxil fumarate [TDF, 300 mg]) or who remained on a zidovudine- plus lamivudine-containing regimen. Subjects continued their protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).
Detailed description
Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (PI or NRTI).
The use of nucleoside analogues, especially stavudine and zidovudine, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances.
As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the European Medicines Agency (EMA) in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection".
In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing zidovudine and lamivudine were randomized to switch to Truvada or to stay on their zidovudine- plus lamivudine-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Truvada | Experimental | Drug: TruvadaTruvada + NNRTI or PI. |
| Zidovudine/lamivudine | Active comparator | Drug: Zidovudine/lamivudineZidovudine/lamivudine + NNRTI or PI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive polymerase chain reaction for HIV-1 ribonucleic acid (RNA).
- Adult patients (over 18 years of age).
- Current HAART regimen containing zidovudine + lamivudine at usual doses for at least 6 months.
- Viral load < 50 copies/mL on the last two consecutive determinations, under zidovudine + lamivudine containing HAART regimen.
- For women of childbearing potential, negative urine pregnancy test at screening visit.
Key exclusion criteria (13 listed)
- Patients on current FTC or TDF therapy.
- Patients with previous history of virological failure on an FTC or TDF-containing regimen.
- Patients receiving a non-registered antiretroviral drug.
- Patients receiving a triple-nucleoside antiretroviral combination.
- Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of those drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TruvadaTruvada once daily with continuation of the current NNRTI or PI at randomization. | Drug | Truvada |
| Zidovudine/lamivudineContinuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization. | Drug | Zidovudine/lamivudine |
Primary outcome
Change From Baseline in Limb Fat at Week 48
Time frame: Baseline to Week 48
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
17 secondary outcomes
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa)
Time frame: Baseline to Week 48
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes)
Time frame: Baseline to Week 48
Change From Baseline in Lactate Concentration
Time frame: Baseline to Week 48
Percentage of Days for Which Participants Were Compliant With Study Drug
Time frame: Baseline to Week 72
Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL
Time frame: 48 weeks
Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL
Time frame: 48 weeks
Percentage of Participants With Virologic Failure
Time frame: 48 weeks
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count
Time frame: Baseline to Week 48
Change From Baseline in Fasting Serum Triglycerides
Time frame: Baseline to Week 48
Change From Baseline in Fasting Total Cholesterol
Time frame: Baseline to Week 48
Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL)
Time frame: Baseline to Week 48
Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL)
Time frame: Baseline to Week 48
Change From Baseline in Hemoglobin
Time frame: Baseline to Week 48
Percent Change From Baseline in Hematocrit
Time frame: Baseline to Week 48
Change From Baseline in Waist Circumference/Hip Circumference Ratio
Time frame: Baseline to Week 48
Percentage of Participants With Any Adverse Event
Time frame: 72 weeks
Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events.
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pedro Ferrer study director
Gilead Sciences, S.L.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Truvada and Zidovudine/lamivudine in people with HIV-1, run by Gilead Sciences at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Limb Fat at Week 48 (time frame: Baseline to Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2015.