HIV InfectionsPhase 2NCT00046033
Comparing Standard-Dose Versus Adjusted-Dose Lopinavir/Ritonavir Therapy in HIV-Infected Persons With Drug Resistance
A Phase 2 study testing Lopinavir/ritonavir, Ritonavir and Saquinavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.
Trial summary
The purpose of this study is to see if adjusting the dose of lopinavir/ritonavir (LPV/r) has a better effect on lowering HIV viral load (the amount of HIV in the blood) compared to taking the standard FDA-approved LPV/r dose. This study will also compare the safety and tolerability of these two types of dosing. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Lopinavir/ritonavir, Ritonavir and Saquinavir
- How many people
- 118 participants
- Where
- 6 sitesUnited States
- Study dates
- Start not givento Mar 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-infection
- Viral load >= 5000 copies/ml within 45 days prior to study entry
- Documented reduction in LPV sensitivity based on results obtained within 45 days prior to study entry
- Prior experience with 2 or more NRTIs for at least 6 months each
- At least 12 weeks of stable antiretroviral treatment that includes at least one PI prior to study entry and may include TDF and/or T-20 for 8 weeks or more immediately prior to study entry
- Negative pregnancy test within 14 days prior to study entry
- Agree not to become pregnant or to impregnate and to use an acceptable form of contraception while receiving study drugs and for 4 weeks after stopping study drugs
Who cannot join
- Pregnant or breast-feeding.
- Certain drugs within 14 days prior to study entry
- Nonnucleoside reverse transcriptase inhibitors (NNRTIs) within 14 days prior to study entry
- History of intolerance to LPV/r, RTV, or TDF and/or their components
- Drug or alcohol use that, in the opinion of the investigator, would interfere with the study
- Require therapy and/or hospitalization due to a serious infection or medical illness that is potentially life-threatening within 14 days prior to study entry
Show all 11Show fewer
- Any condition that, in the opinion of the investigator, would compromise ability to participate in the study
- Unexplained fever for 7 consecutive days or chronic diarrhea within 30 days prior to study entry
- Cancer requiring chemotherapy
- Any immune system drugs, HIV vaccine, or other experimental therapy within 30 days prior to study entry
- Plan to use any PI other than APV, SQV, or LPV/r in the initial study treatment
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Case Western Reserve Univ
Cleveland, Ohio, 44106
Univ of Texas, Galveston
Galveston, Texas, 77555-0435
Univ of Hawaii
Honolulu, Hawaii, 96816-2396
Univ of Miami
Miami, Florida, 33136-1013
NYU/Bellevue
New York, New York, 10016
Univ of Pittsburgh
Pittsburgh, Pennsylvania, 15213-2582
About this study
Official title: A Phase II, Randomized, Open-Label Study Comparing Fixed-Dose Versus Concentration-Adjusted Lopinavir/Ritonavir Therapy in HIV-Infected Subjects on Salvage Therapy
The purpose of this study is to see if adjusting the dose of lopinavir/ritonavir (LPV/r) has a better effect on lowering HIV viral load (the amount of HIV in the blood) compared to taking the standard FDA-approved LPV/r dose. This study will also compare the safety and tolerability of these two types of dosing.
Read the detailed description
Antiretroviral drugs may fail to suppress HIV unless there are adequate amounts of those drugs in the blood. By monitoring the amounts of drugs in the blood and adjusting doses to achieve optimal drug concentrations, response to antiretroviral drugs may improve, especially in patients who have failed previous regimens. This study is designed to evaluate drug monitoring and dose adjustment of protease inhibitors (PIs) in heavily treatment-experienced patients.
Patients will be randomized to receive either a standard dose of LPV/r (Arm A) or a concentration-adjusted dose of LPV/r (Arm B). Concentration-adjusted dosing means that the dose of ritonavir or lopinavir may be increased based on the amount of lopinavir measured in the blood and the results of a drug resistance test. All patients start the study taking LPV/r, tenofovir disoproxil fumarate (TDF), 0 to 2 additional nucleoside reverse transcriptase inhibitors (NRTIs), and saquinavir (SQV) or amprenavir (APV). Only LPV/r, TDF, and SQV will be provided by the study. Other medications taken as part of the antiretroviral regimen must be obtained outside the study.
Patients in Arm A will take the usual approved dose of LPV/r for the first 24 weeks. At Week 24, patients with high viral loads will come to the clinic for a 12-hour LPV blood level measurement to see if the level of LPV needs to be increased. If it does, an additional capsule of ritonavir will be added to the regimen to boost the level of LPV.
Patients in Arm B will have a series of blood draws over a 12-hour period in the clinic, around 14 days after starting the study, to find out if their LPV level needs to be increased. If the LPV level needs to be raised, an additional capsule of ritonavir will be added to the regimen to boost the level of LPV. Patients who had their ritonavir dose adjusted will return to have another 12-hour blood draw around Week 5. If the LPV level still needs to be changed, an additional capsule of LPV/r will be added to the regimen. A third 12-hour blood draw will be performed around Week 8 if a second dose adjustment was necessary.
During the study, patients will visit the clinic weekly through Week 6, again at Week 8, then every 4 weeks thereafter through Week 32. Patients will have blood drawn at certain visits to test for LPV level, viral load, CD4 count, fasting lipids and glucose, and drug resistance.
- Conditions
- HIV Infections
- Being tested
- Lopinavir/ritonavir, Ritonavir, Saquinavir, Tenofovir disoproxil fumarate, Amprenavir
- Keywords
- Dose-Relationship, Drug, HIV Protease Inhibitors, Salvage Therapy, Viral Load, RNA, Viral, Drug Therapy, Combination
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavirDrug
RitonavirDrug
SaquinavirDrug
Tenofovir disoproxil fumarateDrug
AmprenavirDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2002 (estimated)
- Primary completionMar 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 National Institute of Allergy and Infectious Diseases (NIAID)The 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
- 118 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Deborah McMahon, M.D., Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00046033
- Sponsor's protocol ID
- ACTG A5135
- Status last verified
- May 2005
- First submitted
- 18 Sep 2002
- Last updated
- 1 Mar 2011
- Results posted
- No
Publications
Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, Del Giudice P, Montagne N, Schapiro JM, Dellamonica P. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS. 2000 Jul 7;14(10):1333-9. doi: 10.1097/00002030-200007070-00005.
PubMed 10930147Kilby JM, Hill A, Buss N. The effect of ritonavir on saquinavir plasma concentration is independent of ritonavir dosage: combined analysis of pharmacokinetic data from 97 subjects. HIV Med. 2002 Apr;3(2):97-104. doi: 10.1046/j.1468-1293.2002.00090.x.
PubMed 12010356Veldkamp AI, van Heeswijk RP, Mulder JW, Meenhorst PL, Schreij G, van der Geest S, Lange JM, Beijnen JH, Hoetelmans RM. Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):344-9. doi: 10.1097/00126334-200108010-00004.
PubMed 11468422
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Open-Label Study Comparing Fixed-Dose Versus Concentration-Adjusted Lopinavir/Ritonavir Therapy in HIV-Infected Subjects on Salvage Therapy
- ClinicalTrials.gov ID
- NCT00046033
- Acronym / sponsor ID
- ACTG A5135
- Conditions
- HIV Infections
- Keywords
- Dose-Relationship, Drug, HIV Protease Inhibitors, Salvage Therapy, Viral Load, RNA, Viral, Drug Therapy, Combination
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Primary completion
- Mar 2003 (actual)
- First posted
- 19 Sep 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if adjusting the dose of lopinavir/ritonavir (LPV/r) has a better effect on lowering HIV viral load (the amount of HIV in the blood) compared to taking the standard FDA-approved LPV/r dose. This study will also compare the safety and tolerability of these two types of dosing.
Detailed description
Antiretroviral drugs may fail to suppress HIV unless there are adequate amounts of those drugs in the blood. By monitoring the amounts of drugs in the blood and adjusting doses to achieve optimal drug concentrations, response to antiretroviral drugs may improve, especially in patients who have failed previous regimens. This study is designed to evaluate drug monitoring and dose adjustment of protease inhibitors (PIs) in heavily treatment-experienced patients.
Patients will be randomized to receive either a standard dose of LPV/r (Arm A) or a concentration-adjusted dose of LPV/r (Arm B). Concentration-adjusted dosing means that the dose of ritonavir or lopinavir may be increased based on the amount of lopinavir measured in the blood and the results of a drug resistance test. All patients start the study taking LPV/r, tenofovir disoproxil fumarate (TDF), 0 to 2 additional nucleoside reverse transcriptase inhibitors (NRTIs), and saquinavir (SQV) or amprenavir (APV). Only LPV/r, TDF, and SQV will be provided by the study. Other medications taken as part of the antiretroviral regimen must be obtained outside the study.
Patients in Arm A will take the usual approved dose of LPV/r for the first 24 weeks. At Week 24, patients with high viral loads will come to the clinic for a 12-hour LPV blood level measurement to see if the level of LPV needs to be increased. If it does, an additional capsule of ritonavir will be added to the regimen to boost the level of LPV.
Patients in Arm B will have a series of blood draws over a 12-hour period in the clinic, around 14 days after starting the study, to find out if their LPV level needs to be increased. If the LPV level needs to be raised, an additional capsule of ritonavir will be added to the regimen to boost the level of LPV. Patients who had their ritonavir dose adjusted will return to have another 12-hour blood draw around Week 5. If the LPV level still needs to be changed, an additional capsule of LPV/r will be added to the regimen. A third 12-hour blood draw will be performed around Week 8 if a second dose adjustment was necessary.
During the study, patients will visit the clinic weekly through Week 6, again at Week 8, then every 4 weeks thereafter through Week 32. Patients will have blood drawn at certain visits to test for LPV level, viral load, CD4 count, fasting lipids and glucose, and drug resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- HIV-infection
- Viral load >= 5000 copies/ml within 45 days prior to study entry
- Documented reduction in LPV sensitivity based on results obtained within 45 days prior to study entry
- Prior experience with 2 or more NRTIs for at least 6 months each
- At least 12 weeks of stable antiretroviral treatment that includes at least one PI prior to study entry and may include TDF and/or T-20 for 8 weeks or more immediately prior to study entry
Key exclusion criteria (11 listed)
- Pregnant or breast-feeding.
- Certain drugs within 14 days prior to study entry
- Nonnucleoside reverse transcriptase inhibitors (NNRTIs) within 14 days prior to study entry
- History of intolerance to LPV/r, RTV, or TDF and/or their components
- Drug or alcohol use that, in the opinion of the investigator, would interfere with the study
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/ritonavir | Drug | – |
| Ritonavir | Drug | – |
| Saquinavir | Drug | – |
| Tenofovir disoproxil fumarate | Drug | – |
| Amprenavir | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2011.
- Background: PubMed 10930147Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, Del Giudice P, Montagne N, Schapiro JM, Dellamonica P. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS. 2000 Jul 7;14(10):1333-9. doi: 10.1097/00002030-200007070-00005.
- Background: PubMed 12010356Kilby JM, Hill A, Buss N. The effect of ritonavir on saquinavir plasma concentration is independent of ritonavir dosage: combined analysis of pharmacokinetic data from 97 subjects. HIV Med. 2002 Apr;3(2):97-104. doi: 10.1046/j.1468-1293.2002.00090.x.
- Background: PubMed 11468422Veldkamp AI, van Heeswijk RP, Mulder JW, Meenhorst PL, Schreij G, van der Geest S, Lange JM, Beijnen JH, Hoetelmans RM. Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):344-9. doi: 10.1097/00126334-200108010-00004.
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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.
Deborah McMahon, M.D. study chair
University of Pittsburgh
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 Lopinavir/ritonavir, Ritonavir and Saquinavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 7 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 1 Mar 2011. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00046033, which also lists 3 linked publications.
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 1 Mar 2011.