HIV InfectionsPhase 2NCT00000912
A Study on Amprenavir in Combination With Other Anti-HIV Drugs in HIV-Positive Patients
A Phase 2 study testing Indinavir sulfate, Abacavir sulfate and Amprenavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 45 sites in 2 countries.
Trial summary
The purpose of this study is to compare 4 different combinations of anti-HIV drugs and to determine the number of people whose HIV blood levels decrease to 200 copies/ml or less while on the treatment. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Indinavir sulfate, Abacavir sulfate and Amprenavir
- How many people
- 475 participants
- Where
- 45 sitesin 2 countries
- Study dates
- Start not givento May 2000
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients may be eligible for this study if they:
- Are HIV-positive.
- Have current virologic failure (2 consecutive HIV blood levels above 1,000 copies/ml) while on PIs.
- Are over 13 years of age (consent of parent or guardian required if under 18).
- Agree to practice abstinence or use effective methods of birth control during the study and for 90 days after.
Who cannot join
- Patients will not be eligible for this study if they:
- Have hepatitis within 90 days prior to study entry.
- Have a history of a peripheral neuropathy within 60 days of study entry.
- Have an unexplained temperature for a 7-day period.
- Have chronic diarrhea within 30 days prior to study entry.
- Have cancer requiring chemotherapy.
Show all 9Show fewer
- Received any therapy for infection or other illness within 30 days prior to study entry.
- Have received certain other medications.
- Are pregnant or breast-feeding.
Trial locations and contacts
45 sites in 2 countries.
45 sites in 2 countries
United States44 sites
Emory Univ
Atlanta, Georgia, 30308
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
Atlanta, Georgia, 303652225
Johns Hopkins Hosp
Baltimore, Maryland, 21287
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, 02114
Boston Med Ctr
Boston, Massachusetts, 02118
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, 14215
Northwestern Univ Med School
Chicago, Illinois, 60611
Cook County Hosp
Chicago, Illinois, 60612
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, 60612
Univ of Cincinnati
Cincinnati, Ohio, 452670405
Ohio State Univ Hosp Clinic
Columbus, Ohio, 432101228
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262
Duke Univ Med Ctr
Durham, North Carolina, 27710
Univ of Texas Galveston
Galveston, Texas, 775550435
Moses H Cone Memorial Hosp
Greensboro, North Carolina, 27401
Milton S Hershey Med Ctr
Hershey, Pennsylvania, 170330850
Queens Med Ctr
Honolulu, Hawaii, 96816
Univ of Hawaii
Honolulu, Hawaii, 96816
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, 900331079
USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr
Los Angeles, California, 900334508
UCLA CARE Ctr
Los Angeles, California, 90095
Willow Clinic
Menlo Park, California, 94025
Univ of Miami School of Medicine
Miami, Florida, 331361013
Univ of Minnesota
Minneapolis, Minnesota, 55455
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, 70112
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016
Chelsea Ctr
New York, New York, 10021
Cornell Univ Med Ctr
New York, New York, 10021
Mem Sloan - Kettering Cancer Ctr
New York, New York, 10021
Mount Sinai Med Ctr
New York, New York, 10029
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, 19104
Univ of Pittsburgh Med Ctr
Pittsburgh, Pennsylvania, 15213
Univ of Rochester Medical Center
Rochester, New York, 14642
Univ of California / San Diego Treatment Ctr
San Diego, California, 921036325
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, 941102859
San Francisco Gen Hosp
San Francisco, California, 941102859
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, 951282699
Univ of Washington
Seattle, Washington, 981224304
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, 63112
San Mateo AIDS Program / Stanford Univ
Stanford, California, 943055107
Stanford Univ Med Ctr
Stanford, California, 943055107
Tripler Army Med Ctr
Tripler AMC, Hawaii, 96859
Howard Univ
Washington D.C., District of Columbia, 20059
About this study
Official title: A Phase II, Randomized Trial of Amprenavir as Part of Dual Protease Inhibitor Regimens (Placebo-Controlled) in Combination With Abacavir, Efavirenz, and Adefovir Dipivoxil Versus Amprenavir Alone in HIV-Infected Subjects With Prior Exposure to Approved Protease Inhibitors and Loss of Virologic Suppression as Reflected by a Plasma HIV-1 RNA Concentration >= 1,000 Copies/ml
The purpose of this study is to compare 4 different combinations of anti-HIV drugs and to determine the number of people whose HIV blood levels decrease to 200 copies/ml or less while on the treatment. This study evaluates the safety of these drug combinations, which include an experimental protease inhibitor (PI), amprenavir.
Despite the success that many patients have had with PI treatment regimens, there is still a possibility that patients receiving PIs may continue to have high HIV blood levels. Because of this possibility, alternative drug combinations containing PIs are being studied. It appears that amprenavir, when taken with 3 or 4 other anti-HIV drugs, may be effective in patients with prior PI treatment experience.
Read the detailed description
A number of studies both within and outside the ACTG have been initiated or are in development to try to address the issue of alternative treatments for patients who either do not achieve or lose virologic control while receiving protease inhibitors (PIs). Amprenavir (APV) is an attractive candidate to investigate as part of salvage regimens because: 1) it has substantial antiretroviral activity; 2) there are preliminary in vitro and in vivo data that suggest that resistance to this agent may be mediated in part by a unique mutation (I50V); and 3) its cross-resistance profile to the approved PIs is uncertain.
Patients are selectively randomized to 1 of 4 study arms based on prior PI experience. Those randomized to Arms A, B, or C receive 2 PIs, 1 of which is amprenavir (APV), and those randomized to Arm D receive a single PI (APV) as part of their treatment regimen, as follows:
Arm A: APV plus saquinavir soft gel capsule (SQVsgc) plus abacavir (ABC) plus efavirenz (EFV) plus adefovir (ADV).
Arm B: APV plus indinavir (IDV) plus ABC plus EFV plus ADV. Arm C: APV plus nelfinavir (NFV) plus ABC plus EFV plus ADV. Arm D: APV plus placebo (NFV, IDV, or SQVsgc) plus ABC plus EFV plus ADV. All patients receive L-carnitine supplementation. All patients receive clinical physical assessments and laboratory testing during study as follows: Weeks 2, 4, and every 4 weeks thereafter. A primary analysis is performed after the last patient has reached 24 weeks. [AS PER AMENDMENT 3/2/00: At that time, all patients are unblinded to their original treatment assignment.] Patients who experience virologic failure are unblinded and may choose 1 of the following 3 options: Continue study medications open-label, permanently discontinue study medications, or selectively continue study medications [AS PER AMENDMENT 3/2/00: from the arm the patient was originally randomized to] and combine with other approved antiretroviral agents. [AS PER AMENDMENT 3/2/00: For patients adding didanosine (ddI) to their regimens, monitoring for the development of pancreatitis is crucial.] Final evaluations are required for those patients who are off drug during the immediate 8-week period following the last dose of study treatment. Beyond 8 weeks, they are followed for incidence of death, cancer, congenital anomalies, and permanent disabilities. [AS PER AMENDMENT 3/2/00: Gilead Sciences has terminated its U.S. development of ADV for HIV infection. Gilead will continue to supply ADV for patients in ACTG 398 until the study closes. Patients who are receiving ADV at the completion of the study may continue to access ADV through the Expanded Access Program, provided that the physician and patient have determined that continued use of ADV is beneficial.]
- Conditions
- HIV Infections
- Being tested
- Indinavir sulfate, Abacavir sulfate, Amprenavir, Nelfinavir mesylate, Efavirenz
- Keywords
- Placebos, Drug Therapy, Combination, HIV Protease Inhibitors, VX 478, Anti-HIV Agents, Viral Load, efavirenz
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indinavir sulfateDrug
Abacavir sulfateDrug
AmprenavirDrug
Nelfinavir mesylateDrug
EfavirenzDrug
LevocarnitineDrug
Adefovir dipivoxilDrug
SaquinavirDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionMay 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Enrolment
- 475 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Scott Hammer, Study chairJohn Mellors, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000912
- Sponsor's protocol ID
- ACTG 398
- Other IDs
- 11354, Substudy ACTG 5003s
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 29 Oct 2021
- Results posted
- No
Publications
Pfister M, Labbe L, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB; Adult AIDS Clinical Trial Group Study 398. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother. 2003 Jan;47(1):130-7. doi: 10.1128/AAC.47.1.130-137.2003.
PubMed 12499180Pfister M, Labbe L, Lu JF, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB; AIDS Clinical Trial Group Protocol 398 Investigators. Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir. Clin Pharmacol Ther. 2002 Aug;72(2):133-41. doi: 10.1067/mcp.2002.126183.
PubMed 12189360Hammer SM, Vaida F, Bennett KK, Holohan MK, Sheiner L, Eron JJ, Wheat LJ, Mitsuyasu RT, Gulick RM, Valentine FT, Aberg JA, Rogers MD, Karol CN, Saah AJ, Lewis RH, Bessen LJ, Brosgart C, DeGruttola V, Mellors JW; AIDS Clinical Trials Group 398 Study Team. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. JAMA. 2002 Jul 10;288(2):169-80. doi: 10.1001/jama.288.2.169.
PubMed 12095381Sun J, Nagaraj HN, Reynolds NR. Discrete stochastic models for compliance analysis based on an AIDS Clinical Trial Group (ACTG) study. Biom J. 2007 Aug;49(5):731-41. doi: 10.1002/bimj.200610368.
PubMed 17726714Ghosh P, Ghosh K, Tiwari RC. Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints. Stat Med. 2011 Mar 15;30(6):611-26. doi: 10.1002/sim.4119. Epub 2010 Nov 30.
PubMed 21337357
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized Trial of Amprenavir as Part of Dual Protease Inhibitor Regimens (Placebo-Controlled) in Combination With Abacavir, Efavirenz, and Adefovir Dipivoxil Versus Amprenavir Alone in HIV-Infected Subjects With Prior Exposure to Approved Protease Inhibitors and Loss of Virologic Suppression as Reflected by a Plasma HIV-1 RNA Concentration >= 1,000 Copies/ml
- ClinicalTrials.gov ID
- NCT00000912
- Acronym / sponsor ID
- ACTG 398
- Conditions
- HIV Infections
- Keywords
- Placebos, Drug Therapy, Combination, HIV Protease Inhibitors, VX 478, Anti-HIV Agents, Viral Load, efavirenz
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 475 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- May 2000 (actual)
- First posted
- 31 Aug 2001 (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 compare 4 different combinations of anti-HIV drugs and to determine the number of people whose HIV blood levels decrease to 200 copies/ml or less while on the treatment. This study evaluates the safety of these drug combinations, which include an experimental protease inhibitor (PI), amprenavir.
Despite the success that many patients have had with PI treatment regimens, there is still a possibility that patients receiving PIs may continue to have high HIV blood levels. Because of this possibility, alternative drug combinations containing PIs are being studied. It appears that amprenavir, when taken with 3 or 4 other anti-HIV drugs, may be effective in patients with prior PI treatment experience.
Detailed description
A number of studies both within and outside the ACTG have been initiated or are in development to try to address the issue of alternative treatments for patients who either do not achieve or lose virologic control while receiving protease inhibitors (PIs). Amprenavir (APV) is an attractive candidate to investigate as part of salvage regimens because: 1) it has substantial antiretroviral activity; 2) there are preliminary in vitro and in vivo data that suggest that resistance to this agent may be mediated in part by a unique mutation (I50V); and 3) its cross-resistance profile to the approved PIs is uncertain.
Patients are selectively randomized to 1 of 4 study arms based on prior PI experience. Those randomized to Arms A, B, or C receive 2 PIs, 1 of which is amprenavir (APV), and those randomized to Arm D receive a single PI (APV) as part of their treatment regimen, as follows:
Arm A: APV plus saquinavir soft gel capsule (SQVsgc) plus abacavir (ABC) plus efavirenz (EFV) plus adefovir (ADV).
Arm B: APV plus indinavir (IDV) plus ABC plus EFV plus ADV. Arm C: APV plus nelfinavir (NFV) plus ABC plus EFV plus ADV. Arm D: APV plus placebo (NFV, IDV, or SQVsgc) plus ABC plus EFV plus ADV. All patients receive L-carnitine supplementation. All patients receive clinical physical assessments and laboratory testing during study as follows: Weeks 2, 4, and every 4 weeks thereafter. A primary analysis is performed after the last patient has reached 24 weeks. [AS PER AMENDMENT 3/2/00: At that time, all patients are unblinded to their original treatment assignment.] Patients who experience virologic failure are unblinded and may choose 1 of the following 3 options: Continue study medications open-label, permanently discontinue study medications, or selectively continue study medications [AS PER AMENDMENT 3/2/00: from the arm the patient was originally randomized to] and combine with other approved antiretroviral agents. [AS PER AMENDMENT 3/2/00: For patients adding didanosine (ddI) to their regimens, monitoring for the development of pancreatitis is crucial.] Final evaluations are required for those patients who are off drug during the immediate 8-week period following the last dose of study treatment. Beyond 8 weeks, they are followed for incidence of death, cancer, congenital anomalies, and permanent disabilities. [AS PER AMENDMENT 3/2/00: Gilead Sciences has terminated its U.S. development of ADV for HIV infection. Gilead will continue to supply ADV for patients in ACTG 398 until the study closes. Patients who are receiving ADV at the completion of the study may continue to access ADV through the Expanded Access Program, provided that the physician and patient have determined that continued use of ADV is beneficial.]
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Are HIV-positive.
- Have current virologic failure (2 consecutive HIV blood levels above 1,000 copies/ml) while on PIs.
- Are over 13 years of age (consent of parent or guardian required if under 18).
- Agree to practice abstinence or use effective methods of birth control during the study and for 90 days after.
Key exclusion criteria (9 listed)
- Have hepatitis within 90 days prior to study entry.
- Have a history of a peripheral neuropathy within 60 days of study entry.
- Have an unexplained temperature for a 7-day period.
- Have chronic diarrhea within 30 days prior to study entry.
- Have cancer requiring chemotherapy.
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 |
|---|---|---|
| Indinavir sulfate | Drug | – |
| Abacavir sulfate | Drug | – |
| Amprenavir | Drug | – |
| Nelfinavir mesylate | Drug | – |
| Efavirenz | Drug | – |
| Levocarnitine | Drug | – |
| Adefovir dipivoxil | Drug | – |
| Saquinavir | 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 29 Oct 2021.
- Background: PubMed 12499180Pfister M, Labbe L, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB; Adult AIDS Clinical Trial Group Study 398. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother. 2003 Jan;47(1):130-7. doi: 10.1128/AAC.47.1.130-137.2003.
- Background: PubMed 12189360Pfister M, Labbe L, Lu JF, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, Sheiner LB; AIDS Clinical Trial Group Protocol 398 Investigators. Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir. Clin Pharmacol Ther. 2002 Aug;72(2):133-41. doi: 10.1067/mcp.2002.126183.
- Background: PubMed 12095381Hammer SM, Vaida F, Bennett KK, Holohan MK, Sheiner L, Eron JJ, Wheat LJ, Mitsuyasu RT, Gulick RM, Valentine FT, Aberg JA, Rogers MD, Karol CN, Saah AJ, Lewis RH, Bessen LJ, Brosgart C, DeGruttola V, Mellors JW; AIDS Clinical Trials Group 398 Study Team. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. JAMA. 2002 Jul 10;288(2):169-80. doi: 10.1001/jama.288.2.169.
- Results publication: PubMed 17726714Sun J, Nagaraj HN, Reynolds NR. Discrete stochastic models for compliance analysis based on an AIDS Clinical Trial Group (ACTG) study. Biom J. 2007 Aug;49(5):731-41. doi: 10.1002/bimj.200610368.
- Results publication: PubMed 21337357Ghosh P, Ghosh K, Tiwari RC. Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints. Stat Med. 2011 Mar 15;30(6):611-26. doi: 10.1002/sim.4119. Epub 2010 Nov 30.
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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.
Scott Hammer study chair
John Mellors study chair
45 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Indinavir sulfate, Abacavir sulfate and Amprenavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 45 sites in 2 countries.
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 5 inclusion and 9 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 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Puerto Rico. 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 NCT00000912, which also lists 5 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 29 Oct 2021.