HIV InfectionsPhase 2NCT00001095
A Study of Three Anti-HIV Drug Combinations in Patients Who Have Taken Amprenavir
A Phase 2 study testing Indinavir sulfate, Amprenavir and Nevirapine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.
Trial summary
To determine the proportion of patients treated with amprenavir, zidovudine (ZDV), stavudine (D4T) and lamivudine (3TC) whose HIV-1 RNA level remains below the level of detection during 96 weeks of therapy. 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, Amprenavir and Nevirapine
- How many people
- 94 participants
- Where
- 12 sitesUnited States
- Study dates
- Start not givento Oct 1999
- 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
- Concurrent Medication:
- Required:
- Chemoprophylaxis for Pneumocystis carinii pneumonia (for patients with a CD4+ cell count less than or equal to 200 cells/mm3.
- Allowed:
- Topical and/or oral antifungal agents.
- Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections.
Show all 29Show fewer
- Antibiotics.
- Systemic corticosteroid use for 21 days or less.
- Recombinant erythropoietin (rEPO) and granulocyte-colony stimulating factor (G-CSF, filgrastim).
- Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (not as a sole form of contraception), megestrol acetate, and testosterone.
- Alternative therapies such as vitamins, acupuncture, and visualization techniques.
- [AS PER AMENDMENT 2/27/98:
- Current use of triple therapy with amprenavir/3TC/ZDV (or d4T) for Arm A patients.
- Current use of quadruple therapy with IDV/NVP/3TC/d4T for Arm B patients.]
- Patients must have:
- HIV-positive status.
- Successful response to treatment in ACTG 347 as measured by HIV RNA less than 500 copies/ml (Arm A) OR unsuccessful response to treatment in ACTG 347 or another regimen containing amprenavir OR an increase in plasma HIV RNA above the nadir value to greater than 5,000 copies/ml or by at least one log10 at any time (Arm B) OR intolerance to a regimen containing amprenavir.
- Consent for patients less than 18 years of age.
- [AS PER AMENDMENT 2/27/98:
- Arm A patients must have:
- HIV RNA less than 500 copies/ml on at least one occasion within 60 days of entry while previously enrolled in ACTG 347 and in one of the following categories: currently receiving amprenavir/3TC/ZDV (or d4T) or randomized to monotherapy arm of ACTG 347 and received open-label amprenavir/3TC/ZDV (or d4T).
- Arm B patients must have:
- Failed prior amprenavir therapy, whether on ACTG 347 or not, i.e., HIV RNA greater than or equal to 500 copies/ml after at least 16 weeks of amprenavir and confirmed within 1-6 weeks OR treatment failure that mandated early permanent discontinuation of randomized ACTG 347 study drugs and defined as HIV RNA of at least one log 10 above the nadir (to at least 5,000 copies/ml) or HIV RNA level above the baseline value before 16 weeks of amprenavir and confirmed within 1-6 weeks.
- Initially randomized to triple therapy arm of ACTG 347 with two plasma HIV-1 RNA values of at least 500 copies/ml taken within 60 days prior to study entry and at least 1-6 weeks apart or initially receive open-label amprenavir/3TC/ZDV (or d4T) and with two HIV RNA levels of at least 500 copies/ml, regardless of duration of treatment with amprenavir/3TC/ZDV (or d4T).
- Documented intolerance to any of the reverse transcriptase inhibitors or attempted nevirapine therapy allowed. Arm C patients must have:
- Previously enrolled on ACTG 347 and elected to receive a treatment regimen other than amprenavir/3TC/ZDV (or d4T) or IDV/NVP/3TC/d4T.]
- Prior Medication: Required:
- Amprenavir therapy [AS PER AMENDMENT 2/27/98:
- amprenavir therapy (Arm A and B patients only)].
Who cannot join
- Co-existing Condition:
- Patients with the following conditions or symptoms are excluded:
- Arm A:
- Inability to tolerate amprenavir, ZDV, or 3TC.
- Arm B:
- Inability to tolerate d4T, NVP, or 3TC.
Show all 29Show fewer
- Active infection requiring acute treatment within 14 days prior to study entry.
- Malignancy that requires systemic therapy (patients with minimal Kaposi's sarcoma are not excluded provided they do not require systemic therapy).
- [AS PER AMENDMENT 2/27/98:
- Patients with the following conditions or symptoms are excluded: Arm A:
- Any detection of plasma HIV RNA greater than 500 copies/ml after subject has switched to triple therapy for at least 16 weeks.
- Inability to tolerate amprenavir, ZDV (or d4T), or 3TC.
- Malignancy that requires systemic therapy (minimal Kaposi's sarcoma allowed provided systemic therapy is not required) Arm A and B patients only.]
- Concurrent Medication:
- Excluded:
- Non-protocol-specified antiretroviral agents.
- Immunomodulators that affect immunologic or virologic indices, such as systemic corticosteroids (more than 21 days), thalidomide, or cytokines.
- Concomitant use of rifabutin and/or rifampin.
- Investigational drugs without specific approval.
- Systemic cytotoxic chemotherapy.
- Oral astemizole, carbamazepine, dexamethasone, ketoconazole, itraconazole, phenobarbital, phenytoin, terfenadine, cisapride, triazolam, terfenadine, astemizole, and midazolam.
- Prior Medication:
- [AS PER AMENDMENT 2/27/98: Excluded:
- Prior protease inhibitor therapy except amprenavir (Arm A patients).
- Prior protease inhibitor therapy except amprenavir and IDV (Arm B patients).
- Excluded within 14 days prior to entry:
- Investigational drugs or immunomodulators (except amprenavir) without specific consent of protocol chair(s) (Arm A patients).
- Immunomodulators that affect immunologic or virologic indices, such as systemic corticosteroids, thalidomide or cytokines, unless approved by protocol chair(s) (Arm B patients).
- Oral astemizole, carbamazepine, dexamethasone, ketoconazole, itraconazole, phenobarbital, phenytoin, terfenadine, cisapride, triazolam, midazolam, ergot alkaloids, or drugs containing derivatives of ergot alkaloids.]
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Emory Univ
Atlanta, Georgia, 30308
Boston Med Ctr
Boston, Massachusetts, 02118
Beth Israel Deaconess - West Campus
Boston, Massachusetts, 02215
Univ of North Carolina
Chapel Hill, North Carolina, 275997215
Cook County Hosp
Chicago, Illinois, 60612
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, 900331079
Univ of Miami School of Medicine
Miami, Florida, 331361013
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, 19104
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, 63112
Julio Arroyo
West Columbia, South Carolina, 29169
About this study
Official title: A Phase II Study of 1) Amprenavir (141W94/VX478) Plus 3TC Plus ZDV (or d4T) or 2) IDV Plus NVP Plus 3TC Plus d4T in Subjects Previously Treated With Amprenavir and 3) Other Treatment Regimens (Observational ARM) in Subjects Previously Treated With Amprenavir
To determine the proportion of patients treated with amprenavir, zidovudine (ZDV), stavudine (D4T) and lamivudine (3TC) whose HIV-1 RNA level remains below the level of detection during 96 weeks of therapy. To determine the proportion of patients treated with indinavir (IDV), nevirapine (NVP), 3TC, and d4T whose HIV-1 RNA level decreases and then remains below the level of detection, during the 96-week therapy period. To determine the viral effects, safety, tolerability, and pharmacokinetics of amprenavir in combination with zidovudine, stavudine, and lamivudine. [AS PER AMENDMENT 2/27/98: To determine the proportion of patients with undetectable plasma HIV RNA, by treatment and baseline RNA cohort (either detectable or undetectable). To determine the durability of these regimens by estimating the distribution of time to loss of virologic suppression (or equivalently, time to virologic failure), by treatment and baseline RNA cohort.] This study allows patients who have successfully participated in ACTG 347 or other trials involving amprenavir to continue treatment with amprenavir, ZDV, d4T, and 3TC. Additionally, this study provides patients whose HIV-1 RNA was not reduced to undetectable levels or who had a significant increase in plasma levels ("treatment failures") the opportunity to change to a potentially more active regimen that includes indinavir, nevirapine, lamivudine, and stavudine.
Read the detailed description
This study allows patients who have successfully participated in ACTG 347 or other trials involving amprenavir to continue treatment with amprenavir, ZDV, d4T, and 3TC. Additionally, this study provides patients whose HIV-1 RNA was not reduced to undetectable levels or who had a significant increase in plasma levels ("treatment failures") the opportunity to change to a potentially more active regimen that includes indinavir, nevirapine, lamivudine, and stavudine.
Patients with HIV RNA less than 500 copies/ml on a regimen containing amprenavir are treated on Arm A; those with greater than or equal to 500 copies while on or intolerant to a regimen containing amprenavir are treated on Arm B.
Arm A: Amprenavir + ZDV + d4T + 3TC. Arm B: IND + NVP + 3TC + d4T. Patients enrolled in Arm A who fail therapy may roll over to Arm B. Patients in Arm B who fail therapy discontinue study medications and seek best available treatment.
[AS PER AMENDMENT 2/27/98: Patients with HIV RNA less than 500 copies/ml currently on triple therapy with amprenavir + 3TC + ZDV (or d4T if ZDV-intolerant) are treated on ARM A. Patients with HIV RNA greater than or equal to 500 copies/ml, who have been intolerant to a regimen containing amprenavir or who were previously enrolled on ACTG 347 who elected to receive a treatment regimen other than amprenavir + ZDV (or d4T) + 3TC or IDV + NVP + 3TC + d4T or other regimens are assigned to Arm C.
Arm A: Amprenavir + ZDV* plus 3TC. Arm B: IDV + NVP + 3TC + d4T*. Arm C: Observation only. Patients are followed for the duration of the study.
- Patients intolerant of ZDV may elect to receive d4T. Patients intolerant of IDV may take study-provided nelfinavir. *Patients who switched to open-label IDV/NVP/3TC/d4T prior to enrollment on this study and who were intolerant to any of the study medications may enroll into Arm B with appropriate substitution of the intolerant study drug(s).
Patients initially assigned to Arm A who are intolerant of amprenavir or who fail therapy have the option of receiving Arm B therapy. Patients initially assigned to Arm B who are intolerant of any of the assigned study drugs may make an appropriate antiretroviral substitution (with approval of the protocol chair).]
- Conditions
- HIV Infections
- Being tested
- Indinavir sulfate, Amprenavir, Nevirapine, Lamivudine, Stavudine
- Keywords
- Drug Therapy, Combination, Zidovudine, Nevirapine, Stavudine, HIV Protease Inhibitors, Lamivudine, VX 478, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Viral Load
- 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
AmprenavirDrug
NevirapineDrug
LamivudineDrug
StavudineDrug
ZidovudineDrug
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 completionOct 1999
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- 94 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Murphy R, Study chairGulick R, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001095
- Sponsor's protocol ID
- ACTG 373
- Other IDs
- 11334
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Gulick RM, Smeaton LM, D'Aquila RT, Eron JJ, Currier JS, Gerber JG, Acosta E, Sommadossi JP, Tung R, Snyder S, Kuritzkes DR, Murphy RL; AIDS Clinical Trials Group 373 Study Team. Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373. J Infect Dis. 2001 Mar 1;183(5):715-21. doi: 10.1086/318820. Epub 2001 Jan 30.
PubMed 11181147Gulick RM, Smeaton L, D'Aquila RT, Eron JJ, Currier JS, Degruttola V, Gerber JG, Sommadossi JP, Tung R, Kuritzkes DR, Murphy RL. Indinavir (IDV), nevirapine (NVP), stavudine (d4T) and lamivudine (3TC) for amprenavir (APV)-experienced subjects: ACTG 373. 7th Conf Retro and Opportun Infect. 2000 Jan 30 - Feb 2 (abstract no 526)
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of 1) Amprenavir (141W94/VX478) Plus 3TC Plus ZDV (or d4T) or 2) IDV Plus NVP Plus 3TC Plus d4T in Subjects Previously Treated With Amprenavir and 3) Other Treatment Regimens (Observational ARM) in Subjects Previously Treated With Amprenavir
- ClinicalTrials.gov ID
- NCT00001095
- Acronym / sponsor ID
- ACTG 373
- Conditions
- HIV Infections
- Keywords
- Drug Therapy, Combination, Zidovudine, Nevirapine, Stavudine, HIV Protease Inhibitors, Lamivudine, VX 478, Reverse Transcriptase Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Oct 1999 (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.
To determine the proportion of patients treated with amprenavir, zidovudine (ZDV), stavudine (D4T) and lamivudine (3TC) whose HIV-1 RNA level remains below the level of detection during 96 weeks of therapy. To determine the proportion of patients treated with indinavir (IDV), nevirapine (NVP), 3TC, and d4T whose HIV-1 RNA level decreases and then remains below the level of detection, during the 96-week therapy period. To determine the viral effects, safety, tolerability, and pharmacokinetics of amprenavir in combination with zidovudine, stavudine, and lamivudine. [AS PER AMENDMENT 2/27/98: To determine the proportion of patients with undetectable plasma HIV RNA, by treatment and baseline RNA cohort (either detectable or undetectable). To determine the durability of these regimens by estimating the distribution of time to loss of virologic suppression (or equivalently, time to virologic failure), by treatment and baseline RNA cohort.] This study allows patients who have successfully participated in ACTG 347 or other trials involving amprenavir to continue treatment with amprenavir, ZDV, d4T, and 3TC. Additionally, this study provides patients whose HIV-1 RNA was not reduced to undetectable levels or who had a significant increase in plasma levels ("treatment failures") the opportunity to change to a potentially more active regimen that includes indinavir, nevirapine, lamivudine, and stavudine.
Detailed description
This study allows patients who have successfully participated in ACTG 347 or other trials involving amprenavir to continue treatment with amprenavir, ZDV, d4T, and 3TC. Additionally, this study provides patients whose HIV-1 RNA was not reduced to undetectable levels or who had a significant increase in plasma levels ("treatment failures") the opportunity to change to a potentially more active regimen that includes indinavir, nevirapine, lamivudine, and stavudine.
Patients with HIV RNA less than 500 copies/ml on a regimen containing amprenavir are treated on Arm A; those with greater than or equal to 500 copies while on or intolerant to a regimen containing amprenavir are treated on Arm B.
Arm A: Amprenavir + ZDV + d4T + 3TC. Arm B: IND + NVP + 3TC + d4T. Patients enrolled in Arm A who fail therapy may roll over to Arm B. Patients in Arm B who fail therapy discontinue study medications and seek best available treatment.
[AS PER AMENDMENT 2/27/98: Patients with HIV RNA less than 500 copies/ml currently on triple therapy with amprenavir + 3TC + ZDV (or d4T if ZDV-intolerant) are treated on ARM A. Patients with HIV RNA greater than or equal to 500 copies/ml, who have been intolerant to a regimen containing amprenavir or who were previously enrolled on ACTG 347 who elected to receive a treatment regimen other than amprenavir + ZDV (or d4T) + 3TC or IDV + NVP + 3TC + d4T or other regimens are assigned to Arm C.
Arm A: Amprenavir + ZDV* plus 3TC. Arm B: IDV + NVP + 3TC + d4T*. Arm C: Observation only. Patients are followed for the duration of the study.
- Patients intolerant of ZDV may elect to receive d4T. Patients intolerant of IDV may take study-provided nelfinavir. *Patients who switched to open-label IDV/NVP/3TC/d4T prior to enrollment on this study and who were intolerant to any of the study medications may enroll into Arm B with appropriate substitution of the intolerant study drug(s).
Patients initially assigned to Arm A who are intolerant of amprenavir or who fail therapy have the option of receiving Arm B therapy. Patients initially assigned to Arm B who are intolerant of any of the assigned study drugs may make an appropriate antiretroviral substitution (with approval of the protocol chair).]
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 (29 listed)
- Chemoprophylaxis for Pneumocystis carinii pneumonia (for patients with a CD4+ cell count less than or equal to 200 cells/mm3.
- Topical and/or oral antifungal agents.
- Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections.
- Antibiotics.
- Systemic corticosteroid use for 21 days or less.
Key exclusion criteria (29 listed)
- Inability to tolerate amprenavir, ZDV, or 3TC.
- Inability to tolerate d4T, NVP, or 3TC.
- Active infection requiring acute treatment within 14 days prior to study entry.
- Malignancy that requires systemic therapy (patients with minimal Kaposi's sarcoma are not excluded provided they do not require systemic therapy).
- Any detection of plasma HIV RNA greater than 500 copies/ml after subject has switched to triple therapy for at least 16 weeks.
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 | – |
| Amprenavir | Drug | – |
| Nevirapine | Drug | – |
| Lamivudine | Drug | – |
| Stavudine | Drug | – |
| Zidovudine | 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 4 Nov 2021.
- Background: PubMed 11181147Gulick RM, Smeaton LM, D'Aquila RT, Eron JJ, Currier JS, Gerber JG, Acosta E, Sommadossi JP, Tung R, Snyder S, Kuritzkes DR, Murphy RL; AIDS Clinical Trials Group 373 Study Team. Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373. J Infect Dis. 2001 Mar 1;183(5):715-21. doi: 10.1086/318820. Epub 2001 Jan 30.
- BackgroundGulick RM, Smeaton L, D'Aquila RT, Eron JJ, Currier JS, Degruttola V, Gerber JG, Sommadossi JP, Tung R, Kuritzkes DR, Murphy RL. Indinavir (IDV), nevirapine (NVP), stavudine (d4T) and lamivudine (3TC) for amprenavir (APV)-experienced subjects: ACTG 373. 7th Conf Retro and Opportun Infect. 2000 Jan 30 - Feb 2 (abstract no 526)
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Murphy R study chair
Gulick R study chair
12 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 Indinavir sulfate, Amprenavir and Nevirapine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 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 29 inclusion and 29 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 NCT00001095, which also lists 2 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 4 Nov 2021.