Acquired Immune Deficiency SyndromePhase 4NCT00775606
Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease
A Phase 4 study testing Lopinavir 400 mg/ritonavir 100 mg and Efavirenz in people with Acquired Immune Deficiency Syndrome, run by Rush University Medical Center at 4 sites in United States.
Trial summary
The ideal anti-HIV medications for patients with advanced HIV disease is unknown. There is evidence that anti-HIV regimens that contain protease inhibitors can enhance immune function better than regimens that do not contain protease inhibitors. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Acquired Immune Deficiency Syndrome
- What is being tested?
- Lopinavir 400 mg/ritonavir 100 mg and Efavirenz
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2008to Jan 2011
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- HIV-1 infection
- The absence of exclusionary resistance mutations on a genotypic resistance assay
- Antiretroviral (ARV) drug-naïve
- Screening HIV-1 RNA >1000 copies/mL
- Screening CD4+ T-cell count < 200 cells/ml
- Laboratory values obtained within 30 days prior to study entry.
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- Absolute neutrophil count (ANC) >500/mm3
- Hemoglobin >8.0 g/dL
- Platelet count >40,000/mm3
- AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 x ULN
- Total bilirubin <2.5 x ULN
- Calculated creatinine clearance ≥60 mL/min (by Cockcroft-Gault equation)
- For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications.
- Contraception requirements
- Men and women age >18 years and < 60 years.
- Ability and willingness of subject or legal guardian/representative to give written informed consent.
Who cannot join
- Currently breast-feeding.
- Use of immunomodulators, vaccines, growth hormone, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
- Known allergy/sensitivity to study drugs, pneumococcal polysaccharide vaccine, tetanus-diphtheria vaccine
- Receipt of pneumococcal polysaccharide vaccine or tetanus-diphtheria vaccine in the past 5 years.
- Active drug or alcohol use or dependence
- Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 14 days prior to study entry.
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- Requirement for any current medications that are prohibited with any study treatment.
- Evidence of any major resistance-associated mutation on any genotype or evidence of significant resistance on any phenotype performed at any time prior to study entry
- Current or anticipated imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness
- History of, or current bipolar disorder, major depression, schizophrenia or other psychotic disorders
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Rush University Medical Center
Chicago, Illinois, 60612
University of Illinois Medical Center
Chicago, Illinois, 60612
Howard Brown Health Center
Chicago, Illinois, 60613
University of Chicago Hospital
Chicago, Illinois, 60637
About this study
Official title: A Phase 4 Study of the Effect on Immune Reconstitution of a Lopinavir/Ritonavir-Based Versus an Efavirenz-based HAART (Highly Active Antiretroviral Therapy) Regimen in Antiretroviral-Naïve Subjects With Advanced HIV Disease
The ideal anti-HIV medications for patients with advanced HIV disease is unknown. There is evidence that anti-HIV regimens that contain protease inhibitors can enhance immune function better than regimens that do not contain protease inhibitors. This is a study that will determine the difference in immune enhancement capabilities between an anti-HIV regimen that contains the protease inhibitor - lopinavir-ritonavir, and a regimen that contains efavirenz. Both medications are recommended as first line treatments for HIV-infected patients. This study will recruit HIV-positive patients that need to start anti-HIV treatment because their CD4+ T-cells are below 200. The usual threshold for starting treatment is a CD4+ T-cell less than 350. Subjects will be randomized to treatment with either an anti-HIV regimen that contains lopinavir-ritonavir or a regimen that contains efavirenz. The study will determine the difference in immune reconstitution over 24 weeks of treatment with study medications. Among the immune parameters that will be measured is the ability of each subject to respond to vaccination with the tetanus-diphtheria vaccine and the 23-valent pneumococcal vaccine. Both vaccines are also recommended for HIV-positive patients but HIV-positive patients tend to have a lower response rate to these vaccines.
Read the detailed description
DESIGN: ICE-001 is a phase IV, randomized, two-arm unblinded study, comparing the effect on immune reconstitution of open-label ritonavir (RTV)-enhanced lopinavir (LPV) to efavirenz (EFV), in combination with daily emtricitabine (FTC)/tenofovir (TDF) as initial therapy for HIV-1 infection in HIV-infected treatment naïve subjects with CD4+ T-cells less than 200 cells/ml.
DURATION: Subjects will participate in ICE-001 for approximately 48 weeks after starting study treatment.
SAMPLE SIZE: ICE-001 will enroll 60 subjects (30 per treatment arm).
POPULATION: HIV-1-infected, antiretroviral (ARV) drug-naïve (≤7 days of ARV treatment at anytime prior to study entry) men and women between18 to 60 years of age with plasma HIV-1 RNA levels >1000 copies/mL and CD4+ T-cell counts < 200 cells/ml obtained within 90 days prior to study entry.
STRATIFICATION: Subjects will be stratified at screening based on plasma HIV-1 RNA levels <100,000 and ≥100,000 copies/mL.
REGIMEN: At entry subjects will be randomized to one of the following:
- ARM A: LPV 400 mg/RTV 100 mg BID + FTC 200 mg/TDF 300 mg QD
- ARM B: EFV 600 mg QD/FTC 200 mg/TDF 300 mg fixed dose combination QD
The objective is to determine the differences in the degree of immune reconstitution in HIV-infected patients with a CD4+ T-cell count < 200 cells/ml who initiated treatment with LPV/RTV + FTC/TDF compared to EFV/FTC/TDF.
Study visits will occur at screening, pre-entry, entry and weeks 1, 4, 8, 12, 24 and 48 after study entry. Study medications will be provided at entry after randomization. At most study visits, clinical assessments, including histories, physical exams and determination of drug adherence, will occur. Blood for hematologic and metabolic safety assessments and for the assessment of immune parameters will be obtained. Immune parameters that will be measured include levels of T-cell apoptosis, maturation and activation. Frequencies of various T-cell subsets and other lymphocyte populations will also be done. Response to vaccination with tetanus-diphtheria vaccine and 23-valent pneumococcal polysaccharide vaccine (both given at week 8) will be measured.
- Conditions
- Acquired Immune Deficiency Syndrome
- Being tested
- Lopinavir 400 mg/ritonavir 100 mg, Efavirenz
- Keywords
- AIDS, HIV
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir 400 mg/ritonavir 100 mgDrug
Also called Kaletra, Truvada
Lopinavir 400 mg/ritonavir 100 mg fixed dose combination BID + emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
EfavirenzDrug
Also called Atripla
Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
| Study group | Role | What they receive |
|---|---|---|
| ARM A/Lopinavir/ritonavir | Active comparator | Subjects randomized to Arm A initiated Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD Receives: Drug: Lopinavir 400 mg/ritonavir 100 mg |
| ARM B/Efavirenz | Active comparator | Subjects randomized to Arm B initiated Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD Receives: Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ (Cluster of Differentiation 4) T-cell Apoptosis
Change in the percentage of naive CD4 T-cells undergoing apoptosis as measured by propidium iodide staining. This is a lab test that measures the percentage of naive CD4 T-cells that are undergoing cell death. The change in this measure is obtained by determining the difference between the percentage of naive CD4 T-cells undergoing apoptosis at week 24 of treatment and the percentage undergoing apoptosis at baseline.
Measured: 24 weeks from treatment initiation (baseline and week 24)
Secondary outcomes (6)
CD4+ T-cell Change
This measures the change in CD4+ T-cells from baseline to week 24 of treatment.
Measured: 24 weeks after treatment initiation (baseline and week 24)
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency
Naive, central memory, effector memory, and T reg CD4+ T-cell frequency at baseline
Measured: baseline measurements
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency
Naive, central memory and effector memory, and T reg CD4+ T-cell frequency at week 24
Measured: week 24 measurements
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies
Activation and proliferation of CD4+ and CD8+ T cells were measured at baseline
Measured: baseline measurements
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies
Activation of CD4+ and CD8+ T cells were measured at week 24
Measured: week 24 measurements
Response to Immunization With Pneumococcus Polysaccharide and Tetanus-diphtheria Vaccines
Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines was not done due to small sample size
Measured: 4 weeks after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionDec 2010
- Study completionJan 2011
Why it stopped: Study stopped 12/2010 due to poor enrollment. Only 15 of 60 needed enrolled.
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 Acquired Immune Deficiency SyndromeStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Chicago, University of Illinois Chicago, Ruth M. Rothstein CORE Center, Abbott, Gilead Sciences
- Responsible party
- Principal investigator, Beverly E. Sha, Rush University Medical Center
- Investigators
- Allan R. Tenorio, M.D., Study chair, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00775606
- Sponsor's protocol ID
- ICE-001
- Status last verified
- May 2023
- First submitted
- 17 Oct 2008
- Last updated
- 26 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Pitrak DL, Novak RM, Estes R, Tschampa J, Abaya CD, Martinson J, Bradley K, Tenorio AR, Landay AL. Short communication: Apoptosis pathways in HIV-1-infected patients before and after highly active antiretroviral therapy: relevance to immune recovery. AIDS Res Hum Retroviruses. 2015 Feb;31(2):208-16. doi: 10.1089/aid.2014.0038. Epub 2014 Nov 11.
PubMed 25386736
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4 Study of the Effect on Immune Reconstitution of a Lopinavir/Ritonavir-Based Versus an Efavirenz-based HAART (Highly Active Antiretroviral Therapy) Regimen in Antiretroviral-Naïve Subjects With Advanced HIV Disease
- ClinicalTrials.gov ID
- NCT00775606
- Acronym / sponsor ID
- ICE-001
- Conditions
- Acquired Immune Deficiency Syndrome
- Keywords
- AIDS, HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped 12/2010 due to poor enrollment. Only 15 of 60 needed enrolled.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Collaborators
- University of Chicago, University of Illinois Chicago, Ruth M. Rothstein CORE Center, Abbott, Gilead Sciences
- Study start
- Oct 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 20 Oct 2008 (estimated)
- Results
- Posted 29 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ideal anti-HIV medications for patients with advanced HIV disease is unknown. There is evidence that anti-HIV regimens that contain protease inhibitors can enhance immune function better than regimens that do not contain protease inhibitors. This is a study that will determine the difference in immune enhancement capabilities between an anti-HIV regimen that contains the protease inhibitor - lopinavir-ritonavir, and a regimen that contains efavirenz. Both medications are recommended as first line treatments for HIV-infected patients. This study will recruit HIV-positive patients that need to start anti-HIV treatment because their CD4+ T-cells are below 200. The usual threshold for starting treatment is a CD4+ T-cell less than 350. Subjects will be randomized to treatment with either an anti-HIV regimen that contains lopinavir-ritonavir or a regimen that contains efavirenz. The study will determine the difference in immune reconstitution over 24 weeks of treatment with study medications. Among the immune parameters that will be measured is the ability of each subject to respond to vaccination with the tetanus-diphtheria vaccine and the 23-valent pneumococcal vaccine. Both vaccines are also recommended for HIV-positive patients but HIV-positive patients tend to have a lower response rate to these vaccines.
Detailed description
DESIGN: ICE-001 is a phase IV, randomized, two-arm unblinded study, comparing the effect on immune reconstitution of open-label ritonavir (RTV)-enhanced lopinavir (LPV) to efavirenz (EFV), in combination with daily emtricitabine (FTC)/tenofovir (TDF) as initial therapy for HIV-1 infection in HIV-infected treatment naïve subjects with CD4+ T-cells less than 200 cells/ml.
DURATION: Subjects will participate in ICE-001 for approximately 48 weeks after starting study treatment.
SAMPLE SIZE: ICE-001 will enroll 60 subjects (30 per treatment arm).
POPULATION: HIV-1-infected, antiretroviral (ARV) drug-naïve (≤7 days of ARV treatment at anytime prior to study entry) men and women between18 to 60 years of age with plasma HIV-1 RNA levels >1000 copies/mL and CD4+ T-cell counts < 200 cells/ml obtained within 90 days prior to study entry.
STRATIFICATION: Subjects will be stratified at screening based on plasma HIV-1 RNA levels <100,000 and ≥100,000 copies/mL.
REGIMEN: At entry subjects will be randomized to one of the following:
- ARM A: LPV 400 mg/RTV 100 mg BID + FTC 200 mg/TDF 300 mg QD
- ARM B: EFV 600 mg QD/FTC 200 mg/TDF 300 mg fixed dose combination QD
The objective is to determine the differences in the degree of immune reconstitution in HIV-infected patients with a CD4+ T-cell count < 200 cells/ml who initiated treatment with LPV/RTV + FTC/TDF compared to EFV/FTC/TDF.
Study visits will occur at screening, pre-entry, entry and weeks 1, 4, 8, 12, 24 and 48 after study entry. Study medications will be provided at entry after randomization. At most study visits, clinical assessments, including histories, physical exams and determination of drug adherence, will occur. Blood for hematologic and metabolic safety assessments and for the assessment of immune parameters will be obtained. Immune parameters that will be measured include levels of T-cell apoptosis, maturation and activation. Frequencies of various T-cell subsets and other lymphocyte populations will also be done. Response to vaccination with tetanus-diphtheria vaccine and 23-valent pneumococcal polysaccharide vaccine (both given at week 8) will be measured.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A/Lopinavir/ritonavir | Active comparator | Drug: Lopinavir 400 mg/ritonavir 100 mgSubjects randomized to Arm A initiated Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD |
| ARM B/Efavirenz | Active comparator | Drug: EfavirenzSubjects randomized to Arm B initiated Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- HIV-1 infection
- The absence of exclusionary resistance mutations on a genotypic resistance assay
- Antiretroviral (ARV) drug-naïve
- Screening HIV-1 RNA >1000 copies/mL
- Screening CD4+ T-cell count < 200 cells/ml
Key exclusion criteria (10 listed)
- Currently breast-feeding.
- Use of immunomodulators, vaccines, growth hormone, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
- Known allergy/sensitivity to study drugs, pneumococcal polysaccharide vaccine, tetanus-diphtheria vaccine
- Receipt of pneumococcal polysaccharide vaccine or tetanus-diphtheria vaccine in the past 5 years.
- Active drug or alcohol use or dependence
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 |
|---|---|---|
| Lopinavir 400 mg/ritonavir 100 mgAlso: Kaletra, TruvadaLopinavir 400 mg/ritonavir 100 mg fixed dose combination BID + emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD | Drug | ARM A/Lopinavir/ritonavir |
| EfavirenzAlso: AtriplaEfavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD | Drug | ARM B/Efavirenz |
Primary outcome
CD4+ (Cluster of Differentiation 4) T-cell Apoptosis
Time frame: 24 weeks from treatment initiation (baseline and week 24)
Change in the percentage of naive CD4 T-cells undergoing apoptosis as measured by propidium iodide staining. This is a lab test that measures the percentage of naive CD4 T-cells that are undergoing cell death. The change in this measure is obtained by determining the difference between the percentage of naive CD4 T-cells undergoing apoptosis at week 24 of treatment and the percentage undergoing apoptosis at baseline.
6 secondary outcomes
CD4+ T-cell Change
Time frame: 24 weeks after treatment initiation (baseline and week 24)
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency
Time frame: baseline measurements
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency
Time frame: week 24 measurements
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies
Time frame: baseline measurements
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies
Time frame: week 24 measurements
Response to Immunization With Pneumococcus Polysaccharide and Tetanus-diphtheria Vaccines
Time frame: 4 weeks after treatment initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25386736Pitrak DL, Novak RM, Estes R, Tschampa J, Abaya CD, Martinson J, Bradley K, Tenorio AR, Landay AL. Short communication: Apoptosis pathways in HIV-1-infected patients before and after highly active antiretroviral therapy: relevance to immune recovery. AIDS Res Hum Retroviruses. 2015 Feb;31(2):208-16. doi: 10.1089/aid.2014.0038. Epub 2014 Nov 11.
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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.
Allan R. Tenorio, M.D. study chair
Rush University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lopinavir 400 mg/ritonavir 100 mg and Efavirenz in people with Acquired Immune Deficiency Syndrome, run by Rush University Medical Center at 4 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 16 inclusion and 10 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: stopped early, as of the sponsor's last update on 26 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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 29 May 2014). 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?
CD4+ (Cluster of Differentiation 4) T-cell Apoptosis (time frame: 24 weeks from treatment initiation (baseline and week 24)). 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 NCT00775606, 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 26 May 2023.