AzTrials
AzTrials

HIV InfectionsPhase 3NCT00000903

Addition of Efavirenz or Nelfinavir to a Lamivudine/Zidovudine/Indinavir HIV Treatment Regimen

A Phase 3 study testing Indinavir sulfate, Lamivudine/Zidovudine and Nelfinavir mesylate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 50 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To compare time to a virologic failure (first of 2 consecutive plasma HIV RNA levels greater than or equal to 200 copies/ml at or after Week 24) of each 4-drug regimen vs the 3-drug regimen. 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, Lamivudine/Zidovudine and Nelfinavir mesylate
How many people
444 participants
Where
50 sitesin 2 countries
Study dates
Start not givento Jul 2001
Phase
Phase 3
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:
  • Allowed:
  • Chemoprophylaxis for Pneumocystis carinii pneumonia.
  • Topical and oral antifungal agents (except for oral ketoconazole and itraconazole).
  • All antibiotics as clinically indicated (unless otherwise excluded).
  • Treatment, maintenance, or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated (unless otherwise excluded).
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  • Systemic corticosteroids for 21 days or less for acute problems.
  • 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, megestrol acetate, testosterone.
  • Alternative therapies such as vitamins. Patients should report the use of these therapies.
  • [AS PER AMENDMENT 2/16/99: Rifabutin can be administered at a reduced dose.]
  • [AS PER AMENDMENT 4/3/00: Systemic cytotoxic chemotherapy. Study team should be notified.]
  • [AS PER AMENDMENT 4/3/00: Expanded access and compassionate use drugs are allowed as part of Step 2 treatment only.]
  • Allowed with caution:
  • [AS PER AMENDMENT 4/3/00: Viagra (sildenafil citrate) at a reduced dose unless otherwise approved by the protocol chair.]
  • [AS PER AMENDMENT 4/3/00: Lovastatin or simvastatin with PIs is not recommended. Caution should be exercised with the use of all other statins when used concomitantly with PIs.]
  • Concurrent Treatment:
  • Allowed:
  • Alternative therapies such as acupuncture and visualization techniques. Patients should report use of these therapies.
  • Patients must have:
  • Documented HIV-1 infection.
  • CD4 count less than or equal to 200 cells/mm3 or a plasma HIV RNA greater than or equal to 100,000 copies/ml [AS PER AMENDMENT 2/16/99:
  • 80,000 copies/ml] within 60 days prior to entry.
  • Other lab values performed within 14 days prior to entry.
  • Prior Medication:
  • Allowed:
  • Zidovudine (ZDV), didanosine (ddI), stavudine (d4T), or zalcitabine (ddC) therapy alone or in combination any time prior to study entry.

Who cannot join

  • Concurrent Medication:
  • Excluded:
  • All antiretroviral therapies other than study medications. [AS PER AMENDMENT 4/3/00: Compassionate use and expanded access drugs are allowed as part of Step 2 treatment.]
  • Investigational drugs without specific approval from the Study Chair. [AS PER AMENDMENT 4/3/00: Compassionate use and expanded access drugs are allowed as part of Step 2 treatment.]
  • Systemic cytotoxic chemotherapy. [AS PER AMENDMENT 4/3/00: Systemic cytotoxic chemotherapy is allowed. Study team should be notified.]
  • Alprazolam, amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, encainide, ergot alkaloids and derivatives of ergot alkaloids, estazolam, flecainide, flurazepam, itraconazole , ketoconazole, meperidine, midazolam, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, rifampin, terfenadine, triazolam, or zolpidem. [AS PER AMENDMENT 2/16/99: Amiodarone, astemizole, cisapride, ergot alkaloids or drugs containing derivatives of ergot alkaloids, itraconazole, midazolam, triazolam, quinidine, rifampin, terfenadine.] [AS PER AMENDMENT 4/3/00: Amiodarone, astemizole, bepridil, cisapride, ergot alkaloids and derivatives of ergot alkaloids, Hypericum perforatum (St. John's wort), itraconazole, midazolam, quinidine, rifampin, terfenadine, triazolam.]
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  • Vitamin E supplements. [AS PER AMENDMENT 4/3/00: Multivitamins containing vitamin E are allowed.]
  • Avoided:
  • Herbal medications. Patients should report use.
  • Patients with the following prior conditions are excluded:
  • Acute therapy for an infection or other medical illnesses within 14 days prior to study entry. [AS PER AMENDMENT 2/16/99: Acute therapy for a serious infection or other serious medical illnesses that are potentially life-threatening and require systemic therapy and/or hospitalization within 14 days of study entry.]
  • Prior Medication:
  • Excluded within 30 days prior to entry:
  • More than 1 day experience with lamivudine (3TC), nonnucleoside reverse transcriptase inhibitor, or protease inhibitor.
  • Erythropoietin, G-CSF, or GM-CSF.
  • Interferons, interleukins, HIV vaccines, or any experimental therapy.
  • Excluded within 14 days prior to entry:
  • Alprazolam (Xanax), amiodarone (Cordarone), astemizole (Hismanal), bepridil (Vascor), bupropion (Wellbutrin, Zyban), cisapride (Propulsid), clorazepate (Tranxene), clozapine (Clozaril), diazepam (Valium), encainide (Enkaid), ergot alkaloids or drugs containing derivatives of ergot alkaloids, estazolam (ProSom), flecainide (Tambocor), flurazepam (Dalmane), itraconazole (Sporanox), ketoconazole (Nizoral), meperidine (Demerol), midazolam (Versed), piroxicam (Feldene), propafenone (Rythmol), propoxyphene (Darvon, Darvocet), quinidine, rifabutin (Mycobutin), rifampin (Rifadin, Rifamate, Rifater, Rimactane), terfenadine (Seldane), triazolam (Halcion), or zolpidem (Ambien). [AS PER AMENDMENT 2/16/99: Agents excluded within 14 days prior to entry are now as follows:
  • amiodarone, astemizole, cisapride, ergot alkaloids or drugs containing derivatives of ergot alkaloids, itraconazole, midazolam, quinidine, rifampin, terfenadine, and triazolam.
  • Note:
  • Rifabutin can be administered at a reduced dose of 150 mg/day.]

Trial locations and contacts

50 sites in 2 countries.

50 sites in 2 countries

United States49 sites

  • The Ponce de Leon Ctr. CRS

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80262

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • SUNY - Buffalo, Erie County Medical Ctr.

    Buffalo, New York, 14215

  • Unc Aids Crs

    Chapel Hill, North Carolina, 275997215

  • Carolinas HealthCare System, Carolinas Med. Ctr.

    Charlotte, North Carolina, 28203

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Cook County Hosp. CORE Ctr.

    Chicago, Illinois, 60612

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Weiss Memorial Hosp.

    Chicago, Illinois, 60640

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 452670405

  • Case CRS

    Cleveland, Ohio, 44106

  • MetroHealth CRS

    Cleveland, Ohio, 441091998

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio, 432101228

  • Duke Univ. Med. Ctr. Adult CRS

    Durham, North Carolina, 27710

  • Regional Center for Infectious Disease, Wendover Medical Center CRS

    Greensboro, North Carolina, 27401

  • Queens Med. Ctr.

    Honolulu, Hawaii, 96816

  • Univ. of Hawaii at Manoa, Leahi Hosp.

    Honolulu, Hawaii, 96816

  • Indiana Univ. School of Medicine, Wishard Memorial

    Indianapolis, Indiana, 462025250

  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic

    Indianapolis, Indiana, 46202

  • Methodist Hosp. of Indiana

    Indianapolis, Indiana, 46202

  • Univ. of Iowa Healthcare, Div. of Infectious Diseases

    Iowa City, Iowa, 52242

  • USC CRS

    Los Angeles, California, 900331079

  • UCLA CARE Center CRS

    Los Angeles, California, 90095

  • Univ. of Miami AIDS CRS

    Miami, Florida, 331361013

  • University of Minnesota, ACTU

    Minneapolis, Minnesota, 55455

  • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

    New Orleans, Louisiana, 70112

  • Beth Israel Med. Ctr., ACTU

    New York, New York, 10003

  • Cornell CRS

    New York, New York, 10021

  • Beth Israel Med. Ctr. (Mt. Sinai)

    New York, New York, 10029

  • Cornell University A2201

    New York, New York

  • NY Univ. HIV/AIDS CRS

    New York, New York

  • Weill Med. College of Cornell Univ., The Cornell CTU

    New York, New York

  • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

    Omaha, Nebraska, 681985130

  • Stanford CRS

    Palo Alto, California

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania, 19104

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Ucsd, Avrc Crs

    San Diego, California, 92161

  • Ucsf Aids Crs

    San Francisco, California, 941102859

  • Santa Clara Valley Med. Ctr.

    San Jose, California, 951282699

  • San Mateo County AIDS Program

    San Mateo, California

  • Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic

    San Rafael, California

  • University of Washington AIDS CRS

    Seattle, Washington, 981224304

  • St. Louis ConnectCare, Infectious Diseases Clinic

    St Louis, Missouri, 63112

  • Washington U CRS

    St Louis, Missouri

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

  • Howard University Hosp., Div. of Infectious Diseases, ACTU

    Washington D.C., District of Columbia, 20059

Other trials in United States

Puerto Rico1 site

  • Puerto Rico-AIDS CRS

    San Juan, 009365067

Other trials in Puerto Rico

About this study

Official title: A Phase III Randomized, Controlled Trial of Efavirenz (EFV) or Nelfinavir (NFV) in Combination With Fixed-Dose Combination Lamivudine/Zidovudine (3TC/ZDV) and Indinavir (IDV) in HIV-Infected Subjects With Less Than or Equal to 200 CD4 Cells/mm3 or Greater Than or Equal to 80,000 HIV RNA Copies/ml in Plasma

To compare time to a virologic failure (first of 2 consecutive plasma HIV RNA levels greater than or equal to 200 copies/ml at or after Week 24) of each 4-drug regimen vs the 3-drug regimen. To determine the safety, tolerance, and virologic benefits of either nelfinavir (NFV) or efavirenz (EFV) with indinavir/lamivudine/zidovudine (IDV/3TC/ZDV) vs IDV/3TC/ZDV alone, in the treatment of patients with advanced HIV disease who have received limited or no prior antiretroviral therapy.

Prior ACTG studies have shown that the 3-drug combination regimen (IDV/ZDV/3TC) resulted in improved clinical outcomes and therefore may prolong the effects of therapy. The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns. Due to the progressive success of combination regimens, it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses. In light of the additive suppression of HIV replication determined by pharmacological, immunological, and virological results, nelfinavir (NFV) as an addition to IDV/ZDV/3TC will be evaluated. Based on the potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs, efavirenz (EFV) will also be evaluated as an addition to IDV/ZDV/3TC.

Read the detailed description

Prior ACTG studies have shown that the 3-drug combination regimen (IDV/ZDV/3TC) resulted in improved clinical outcomes and therefore may prolong the effects of therapy. The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns. Due to the progressive success of combination regimens, it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses. In light of the additive suppression of HIV replication determined by pharmacological, immunological, and virological results, nelfinavir (NFV) as an addition to IDV/ZDV/3TC will be evaluated. Based on the potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs, efavirenz (EFV) will also be evaluated as an addition to IDV/ZDV/3TC.

Patients with HIV infection, CD4 cell count less than or equal to 200 cells/mm3 or plasma HIV RNA greater than or equal to 100,000 copies/ml, and limited (no prior 3TC, NNRTI, or protease inhibitor) or no prior antiretroviral treatment are randomized to 1 of 3 arms. Patients are stratified by CD4 cell count (less than or equal to 50 cells/mm3 vs greater than 50 cells/mm3), HIV-1 RNA copy number (less than or equal to 40,000 copies/ml vs greater than 40,000 copies/ml), and prior antiretroviral therapy (no therapy vs any therapy), and then randomly assigned to 1 of 3 treatment arms:

Arm 1: 3TC plus ZDV plus IDV. Arm 2: 3TC plus ZDV plus IDV plus EFV. Arm 3: 3TC plus ZDV plus IDV plus NFV. Patients are followed for at least 72 weeks [AS PER AMENDMENT 2/16/99: 96 weeks] beyond the enrollment of the last patient. Patients who experience virologic relapse will have the option of continuing randomized study medications, switching to Step 2 treatment, switching to another ACTG study, or seeking best available therapy for the remaining weeks of the study. Step 2 treatment consists of abacavir or 2 NNRTIs plus efavirenz plus amprenavir or another protease inhibitor. [AS PER AMENDMENT 4/3/00: Optimally, Step 2 treatment regimens should contain 3 or 4 drugs to which the virus is susceptible. If this is not possible, a drug to which the virus is partially susceptible is acceptable, but a drug to which the virus is resistant should not be included.]

Conditions
HIV Infections
Being tested
Indinavir sulfate, Lamivudine/Zidovudine, Nelfinavir mesylate, Efavirenz
Keywords
Drug Therapy, Combination, Zidovudine, HIV Protease Inhibitors, Lamivudine, Indinavir, RNA, Viral, Reverse Transcriptase Inhibitors, Nelfinavir, 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

  • Lamivudine/ZidovudineDrug

  • Nelfinavir mesylateDrug

  • EfavirenzDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionJul 2001

Resources

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 3
Primary purpose
Treatment
Masking
None (open label)
Enrolment
444 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000903
Sponsor's protocol ID
ACTG 388
Other IDs
11347, Substudy ACTG 734, Substudy ACTG A5060s, Substudy ACTG 732, Substudy ACTG 733, Substudy ACTG 735, Substudy ACTG 737, Substudy ACTG 746
Status last verified
May 2012
First submitted
2 Nov 1999
Last updated
21 May 2012
Results posted
No

Publications

  • Fischl MA, Ribaudo HJ, Collier AC, Erice A, Giuliano M, Dehlinger M, Eron JJ Jr, Saag MS, Hammer SM, Vella S, Morse GD, Feinberg JE, Demeter LM, Eshleman SH; Adult AIDS Clinical Trials Group 388 Study Team. A randomized trial of 2 different 4-drug antiretroviral regimens versus a 3-drug regimen, in advanced human immunodeficiency virus disease. J Infect Dis. 2003 Sep 1;188(5):625-34. doi: 10.1086/377311. Epub 2003 Aug 15.

    PubMed 12934177

  • Demeter LM, Ribaudo HJ, Erice A, Eshleman SH, Hammer SM, Hellmann NS, Fischl MA; AIDS Clinical Trials Group Protocol 388. HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing: a substudy of AIDS Clinical Trials Group Protocol 388. Clin Infect Dis. 2004 Aug 15;39(4):552-8. doi: 10.1086/422518. Epub 2004 Jul 30.

    PubMed 15356820

  • DiCenzo R, Forrest A, Fischl MA, Collier A, Feinberg J, Ribaudo H, DiFrancecso R, Morse GD; AIDS Clinical Trials Group 388/733/5060 Study Team. Pharmacokinetics of indinavir and nelfinavir in treatment-naive, human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2004 Mar;48(3):918-23. doi: 10.1128/AAC.48.3.918-923.2004.

    PubMed 14982784

  • Lok JJ, Hunt PW, Collier AC, Benson CA, Witt MD, Luque AE, Deeks SG, Bosch RJ. The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy. AIDS. 2013 Aug 24;27(13):2101-10. doi: 10.1097/QAD.0b013e32836191b1.

    PubMed 24326304

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Indinavir sulfate, Lamivudine/Zidovudine and Nelfinavir mesylate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 50 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 27 inclusion and 21 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 21 May 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 NCT00000903, which also lists 4 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 21 May 2012.

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