HIV InfectionsPhase 2NCT00752856
Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients
A Phase 2 study testing Kaletra + Isentress and Atripla in people with HIV Infections, run by University of California, San Diego at 6 sites in United States.
Trial summary
CCTG 589 is a randomized, open-label, pilot study comparing the efficacy, safety and tolerability of RAL plus LPV/r to EFV plus TDF/FTC in HIV-infected, treatment-naïve subjects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Kaletra + Isentress and Atripla
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 6 sitesUnited States
- Study dates
- 26 Aug 2008to 11 Feb 2014
- Phase
- Phase 2
- 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
- Documented HIV-1 infection.
- Treatment naïve (defined as having never received any HIV antiretroviral agents in past).
- CD4+ T-cell count greater than or equal to 50 cells/mm3
- HIV viral load greater than or equal to 5,000 copies/mL
- Laboratory values obtained by screening laboratories within 30 days of entry:
- Absolute neutrophil count (ANC) greater than 750/mm3.
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- Hemoglobin greater than 8.0 g/dL.
- Platelet count greater than 50,000/mm3.
- Calculated creatinine clearance (CrCl) > 60 mL/min as estimated by the Cockcroft-Gault equation:
- For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)
- For women, multiply the result by 0.85 = CrCl (mL/min)
- AST (SGOT), ALT (SGPT), and alkaline phosphatase less than 5 x ULN.
- Total bilirubin less than 2.5 x ULN.
- Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
- Men and women age greater than or equal to 18 years.
- Ability to obtain prescription for HIV antiretroviral medications and to have required prescriptions filled prior to entry.
- Ability and willingness of subject to give written informed consent
Who cannot join
- Pregnancy or breast-feeding
- Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry (day 0).
- Acute therapy for serious infection or other serious medical illnesses (in the judgment of the site investigator) requiring systemic treatment and/or hospitalization within 14 days prior to study entry (day 0).
- Evidence of HIV seroconversion within 6 months prior to study entry.
- Evidence of any major HIV drug resistance-associated mutation on any genotype performed prior to study entry or at the time of screening.
- History of chronic hepatitis C (defined as HCV antibody positive and HCV RNA detectable).
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- History of chronic active hepatitis B (defined as surface antigen positive and/or HBV DNA detectable).
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.
- Use of human growth hormone within 30 days prior to study entry.
- Initiation of testosterone or anabolic steroids within 30 days prior to study entry. (Exception: Chronic replacement dosages in patient's with diagnosed hypogonadism is allowed).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Living Hope Clinical Foundation
Long Beach, California, 90813
University Southern California
Los Angeles, California, 90033
Univerisity California Irvine
Orange, California, 92868
Desert AIDS Project
Palm Springs, California, 92262
University California San Diego
San Diego, California, 92103
Harbor-UCLA
Torrance, California, 90502
About this study
Official title: Nucleoside-Sparing Combination Therapy With Lopinavir/Ritonavir (LPV/r) + Raltegravir (RAL) vs. Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Patients
CCTG 589 is a randomized, open-label, pilot study comparing the efficacy, safety and tolerability of RAL plus LPV/r to EFV plus TDF/FTC in HIV-infected, treatment-naïve subjects. Subjects will be ineligible if they have any evidence of drug resistant virus in the past or at the time of screening (if never previously tested). Those who are found to be eligible will be randomized 1:1 to initiate either LPV/r (400/100 mg) plus RAL (400mg), both given twice-daily, or fixed dose combination of EFV (600 mg), TDF (300 mg) and FTC (200 mg) given as once-daily Atripla® for 48 weeks.
Hypotheses
- The novel nucleoside-sparing combination of LPV/r + RAL will have a faster phase 1 viral decay rate compared to standard-of-care therapy with EFV/TDF/FTC in antiretroviral-naïve patients.
- Faster phase 1 viral decay dynamics will be associated with improved longer-term (week 48) viral suppression.
- Faster phase 1 viral decay dynamics will be associated with accelerated early (Day 0-14) clearance of cell-associated HIV DNA.
- Faster phase 1 viral decay dynamics will be associated with greater early (baseline to week 12) CD4+ T-cell recovery.
- The LPV/r + RAL arm will have greater decreases in early (baseline to week 4) CD4/CD8 T-cell immune activation and apoptosis which will be associated with greater late (week 12 to week 48) CD4+ T-cell recovery.
- Subjects treated with LPV/r + RAL arm will have smaller changes in total cholesterol and triglycerides from baseline than those receiving EFV/TDF/FTC.
Read the detailed description
The purpose of this study is to determine how well a new anti-HIV drug combination (RAL plus LPV/r) taken twice a day decreases the amount of HIV found in participants' blood (viral load) compared to taking the once-a-day combination pill Atripla®. This study will also try to determine if the new combination has fewer side effects and is tolerated better than Atripla®. Another reason this study is being done is to see if this new drug combination helps participants' body's CD4 cells recover differently and will also look at how well participants' bodies absorbs these drugs and how safe these drugs are when given together.
- Conditions
- HIV Infections
- Being tested
- Kaletra + Isentress, Atripla
- Keywords
- HIV treatment, Treatment-naive, Adult
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kaletra + IsentressDrug
Also called Lopinavir/ritonavir (LPV/r) + Raltegravir (RAL)
kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day
AtriplaDrug
Also called Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC)
Atripla 1 tab once a day
| Study group | Role | What they receive |
|---|---|---|
| 1 - Kaletra + Isentress taken twice daily | Experimental | Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Receives: Drug: Kaletra + Isentress |
| 2 - Atripla taken once daily | Active comparator | Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Receives: Drug: Atripla |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Compare the Phase 1 Viral Decay Rates Between LPV/r + RAL vs. EFV/TDF/FTC Treatment Combinations.
Repeated HIV RNA measured at different time points (baseline, days 2, 7, 10, 14) will be treated as the outcome variable in a linear mixed-effects model. The primary fixed effects will include time, treatment group, treatment group-by-time interaction; random effects will include both intercept and slope allowing each subject to have individual baseline viral load and viral decay (rate of decrease in viral load following initiation of antiretroviral therapy). The treatment group-by- time interaction term in the model will indicate the difference in viral decay rates between the two treatment groups. Baseline covariate adjustment will be included if necessary.
Measured: Baseline, days 2, 7, 10, 14
Secondary outcomes (3)
Viral Suppression Efficacy at 48 Weeks
To determine the antiviral efficacy of LPV/r + RAL compared to EFV/TDF/FTC after 48 weeks of treatment by achieving undetectable viral load
Measured: 48 weeks
Compare Early Activated CD4+ T-cell Recovery Rates From Baseline to Week 4.
To compare early (baseline to Week 4) activated CD4+ T-cell recovery rates between treatment regimens.
Measured: Baseline to Week 4
Compare Late Activated CD4+ T-cell Recovery Rates Between Treatment Regimens From Baseline to Week 48
To compare late (baseline to Week 48) activated CD4+ T-cell recovery rates between treatment regimens.
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 posted16 Sep 2008 (estimated)
- Study start26 Aug 2008
- Primary completion5 May 2011
- Study completion11 Feb 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- California HIV/AIDS Research Program, Merck Sharp & Dohme LLC, Abbott
- Responsible party
- Principal investigator, Sheldon Morris, University of California, San Diego
- Investigators
- Richard Haubrich, MD, Principal investigator, California Collaborative Treatment Group (CCTG)Sheldon Morris, MD, Study chair, UC San Diego AntiViral Research Center (AVRC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00752856
- Sponsor's protocol ID
- CCTG 589
- Status last verified
- Jul 2020
- First submitted
- 13 Sep 2008
- Last updated
- 22 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Karris MY, Jain S, Bowman VQ, Rieg G, Goicoechea M, Dube MP, Kerkar S, Kemper C, Diamond C, Sun X, Daar ES, Haubrich RH, Morris S; California Collaborative Treatment Group (CCTG) 589 Study Team. Nucleoside-Sparing Regimens With Raltegravir and a Boosted Protease Inhibitor: An Unsettled Issue. J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):e48-50. doi: 10.1097/QAI.0000000000000990. No abstract available.
PubMed 26977746
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nucleoside-Sparing Combination Therapy With Lopinavir/Ritonavir (LPV/r) + Raltegravir (RAL) vs. Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Patients
- ClinicalTrials.gov ID
- NCT00752856
- Acronym / sponsor ID
- CCTG 589
- Conditions
- HIV Infections
- Keywords
- HIV treatment, Treatment-naive, Adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- California HIV/AIDS Research Program, Merck Sharp & Dohme LLC, Abbott
- Study start
- 26 Aug 2008 (actual)
- Primary completion
- 5 May 2011 (actual)
- Study completion
- 11 Feb 2014 (actual)
- First posted
- 16 Sep 2008 (estimated)
- Results
- Posted 7 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CCTG 589 is a randomized, open-label, pilot study comparing the efficacy, safety and tolerability of RAL plus LPV/r to EFV plus TDF/FTC in HIV-infected, treatment-naïve subjects. Subjects will be ineligible if they have any evidence of drug resistant virus in the past or at the time of screening (if never previously tested). Those who are found to be eligible will be randomized 1:1 to initiate either LPV/r (400/100 mg) plus RAL (400mg), both given twice-daily, or fixed dose combination of EFV (600 mg), TDF (300 mg) and FTC (200 mg) given as once-daily Atripla® for 48 weeks.
Hypotheses
- The novel nucleoside-sparing combination of LPV/r + RAL will have a faster phase 1 viral decay rate compared to standard-of-care therapy with EFV/TDF/FTC in antiretroviral-naïve patients.
- Faster phase 1 viral decay dynamics will be associated with improved longer-term (week 48) viral suppression.
- Faster phase 1 viral decay dynamics will be associated with accelerated early (Day 0-14) clearance of cell-associated HIV DNA.
- Faster phase 1 viral decay dynamics will be associated with greater early (baseline to week 12) CD4+ T-cell recovery.
- The LPV/r + RAL arm will have greater decreases in early (baseline to week 4) CD4/CD8 T-cell immune activation and apoptosis which will be associated with greater late (week 12 to week 48) CD4+ T-cell recovery.
- Subjects treated with LPV/r + RAL arm will have smaller changes in total cholesterol and triglycerides from baseline than those receiving EFV/TDF/FTC.
Detailed description
The purpose of this study is to determine how well a new anti-HIV drug combination (RAL plus LPV/r) taken twice a day decreases the amount of HIV found in participants' blood (viral load) compared to taking the once-a-day combination pill Atripla®. This study will also try to determine if the new combination has fewer side effects and is tolerated better than Atripla®. Another reason this study is being done is to see if this new drug combination helps participants' body's CD4 cells recover differently and will also look at how well participants' bodies absorbs these drugs and how safe these drugs are when given together.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 - Kaletra + Isentress taken twice daily | Experimental | Drug: Kaletra + IsentressKaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily |
| 2 - Atripla taken once daily | Active comparator | Drug: AtriplaSustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Documented HIV-1 infection.
- Treatment naïve (defined as having never received any HIV antiretroviral agents in past).
- CD4+ T-cell count greater than or equal to 50 cells/mm3
- HIV viral load greater than or equal to 5,000 copies/mL
- Laboratory values obtained by screening laboratories within 30 days of entry:
Key exclusion criteria (11 listed)
- Pregnancy or breast-feeding
- Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry (day 0).
- Acute therapy for serious infection or other serious medical illnesses (in the judgment of the site investigator) requiring systemic treatment and/or hospitalization within 14 days prior to study entry (day 0).
- Evidence of HIV seroconversion within 6 months prior to study entry.
- Evidence of any major HIV drug resistance-associated mutation on any genotype performed prior to study entry or at the time of screening.
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 |
|---|---|---|
| Kaletra + IsentressAlso: Lopinavir/ritonavir (LPV/r) + Raltegravir (RAL)kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day | Drug | 1 - Kaletra + Isentress taken twice daily |
| AtriplaAlso: Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC)Atripla 1 tab once a day | Drug | 2 - Atripla taken once daily |
Primary outcome
To Compare the Phase 1 Viral Decay Rates Between LPV/r + RAL vs. EFV/TDF/FTC Treatment Combinations.
Time frame: Baseline, days 2, 7, 10, 14
Repeated HIV RNA measured at different time points (baseline, days 2, 7, 10, 14) will be treated as the outcome variable in a linear mixed-effects model. The primary fixed effects will include time, treatment group, treatment group-by-time interaction; random effects will include both intercept and slope allowing each subject to have individual baseline viral load and viral decay (rate of decrease in viral load following initiation of antiretroviral therapy). The treatment group-by- time interaction term in the model will indicate the difference in viral decay rates between the two treatment groups. Baseline covariate adjustment will be included if necessary.
3 secondary outcomes
Viral Suppression Efficacy at 48 Weeks
Time frame: 48 weeks
Compare Early Activated CD4+ T-cell Recovery Rates From Baseline to Week 4.
Time frame: Baseline to Week 4
Compare Late Activated CD4+ T-cell Recovery Rates Between Treatment Regimens From Baseline to Week 48
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 22 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26977746Karris MY, Jain S, Bowman VQ, Rieg G, Goicoechea M, Dube MP, Kerkar S, Kemper C, Diamond C, Sun X, Daar ES, Haubrich RH, Morris S; California Collaborative Treatment Group (CCTG) 589 Study Team. Nucleoside-Sparing Regimens With Raltegravir and a Boosted Protease Inhibitor: An Unsettled Issue. J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):e48-50. doi: 10.1097/QAI.0000000000000990. No abstract available.
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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.
Richard Haubrich, MD principal investigator
California Collaborative Treatment Group (CCTG)
Sheldon Morris, MD study chair
UC San Diego AntiViral Research Center (AVRC)
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Kaletra + Isentress and Atripla in people with HIV Infections, run by University of California, San Diego at 6 sites in United States.
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 17 inclusion and 11 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 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Jul 2020). 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?
To Compare the Phase 1 Viral Decay Rates Between LPV/r + RAL vs. EFV/TDF/FTC Treatment Combinations. (time frame: Baseline, days 2, 7, 10, 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00752856, which also lists 1 linked publication.
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 22 Jul 2020.