A Study of Three Treatment Combinations Using Zidovudine Plus Lamivudine Plus Indinavir in HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001084
First received: November 2, 1999
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

To compare the proportion of patients who sustain suppression of plasma HIV RNA to undetectable levels [AS PER AMENDMENT 09/19/97: below 200 copies/mL by Roche UltraSensitive assay] among the 3 regimens during the maintenance phase.

The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Prospective Randomized Double-Blind Trial of Three Maintenance Regimens for HIV-Infected Subjects Receiving Induction Therapy With Zidovudine, Lamivudine and Indinavir

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 500
Study Completion Date: December 1997
Detailed Description:

The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.

All patients will receive open label induction therapy with zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV) for 6 months. Following the 6 month induction phase, patients with undetectable plasma HIV RNA at weeks 16, 20 and 24 will enter the maintenance phase [blinded maintenance phase AS PER AMENDMENT 09/19/97] and be randomized to one of three maintenance regimens, i.e., either continued ZDV/3TC/IDV (control), or ZDV/3TC/IDV placebo or ZDV placebo/3TC placebo/IDV. Prior to randomization, patients are stratified according to entry HIV RNA level (greater than or equal to 30,000 or less than 30,000 copies/ml) and by prior ZDV therapy (at least 7 days or less than 7 days). After 12 months [AS PER AMENDMENT 09/19/97: 18 months] of maintenance therapy, treatment will be withdrawn at 6-month intervals in randomly-selected patients who have achieved undetectable HIV RNA. AS PER 09/19/97 AMENDMENT: After 18 months of blinded maintenance therapy, treatment is unblinded for patients whose HIV RNA levels remain detectable. Such patients receive optimal therapy, either continuing the protocol regimen or initiating alternative therapy.

AS PER AMENDMENT 2/27/98: An interim review conducted in January, 1998 demonstrated that the strategy of less intensive antiviral therapy after 6 months of IDV/3TC/ZDV induction therapy is less effective than continuation of triple drug therapy except for ZDV-naive patients assigned to ZDV/3TC. Therefore, the maintenance phase of this study has been discontinued.

Patients currently on blinded maintenance are unblinded immediately and have the option of reinitiating open-label triple therapy with IDV/3TC/ZDV or discontinuing study treatment. Patients currently on induction may register for continued open-label triple therapy or may discontinue study treatment. This amendment allows treatment extension so that subjects may receive open-label triple therapy until May 31, 1998. At that time, a rollover protocol or another modification with a longer period of drug supply may become available. Patients who choose to go off treatment are followed until May 31, 1998.

AS PER AMENDMENT 04/23/98: This study will now provide treatment with open-label ZDV/3TC/IDV until August 1, 1998. A rollover protocol or another 343 protocol modification with a longer period of drug supply may become available, but this cannot be guaranteed.

AS PER AMENDMENT 06/19/98: This study will now provide treatment with open-label ZDV/3TC/IDV until either November 1, 1998 or until 3 months after the rollover study (A5025) is available to the study sites (whichever comes first).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients must have:

  • Documented HIV infection.
  • A CD4 cell count >= 200 cells/mm3 within 90 days prior to study entry.
  • Plasma HIV RNA >= 1000 copies/ml within 90 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following conditions or symptoms are excluded:

  • A malignancy that requires systemic chemotherapy.

Concurrent Medication:

Excluded:

  • Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion) or midazolam (Versed).
  • All antiretroviral therapies other than study medications.
  • Rifabutin and rifampin.
  • Investigational drugs and vaccines.
  • Systemic cytotoxic chemotherapy.
  • Interferon, interleukins, GM-CSF and HIV vaccines.

Patients with any of the following prior conditions are excluded:

  • Unexplained temperature > 38.5 degrees C for any 7 days within 30 days prior to study entry.
  • Chronic diarrhea as defined as > 3 liquid stools per day persisting for 15 days within 30 days prior to study entry.
  • Proven or suspected acute hepatitis within 30 days prior to study entry, even if AST and ALT are <= 5.0 X ULN (upper limit of normal).
  • A history of >= Grade 2 bilateral peripheral neuropathy within 60 days prior to study entry.
  • A history of intolerance to 300 mg/day of ZDV defined as any toxicity requiring a dose reduction or termination of ZDV.

Prior Medication:

Excluded:

  • Acute therapy for an infection or other medical illness within 14 days prior to study entry.
  • Any prior therapy with 3TC or experimental drug 1592.
  • More than 2 weeks of lifetime exposure to protease inhibitor therapy; any exposure within 14 days prior to study entry.
  • Interferons, interleukins, GM-CSF or HIV vaccines within 30 days prior to study entry.
  • Any experimental therapy (drugs or vaccines) within 30 days prior to study entry.
  • Rifampin or rifabutin within 14 days prior to study entry.
  • Systemic cytotoxic chemotherapy within 30 days prior to study entry.
  • Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion) or midazolam (Versed).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001084

  Hide Study Locations
Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Georgia
Emory Univ
Atlanta, Georgia, United States, 30308
United States, Hawaii
Queens Med Ctr
Honolulu, Hawaii, United States, 96816
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Cook County Hosp
Chicago, Illinois, United States, 60612
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
United States, Indiana
Division of Inf Diseases/ Indiana Univ Hosp
Indianapolis, Indiana, United States, 46202
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Iowa
Univ of Iowa Hosp and Clinic
Iowa City, Iowa, United States, 52242
United States, Louisiana
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
Tulane Med Ctr Hosp
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
Hennepin County Med Clinic
Minneapolis, Minnesota, United States, 55415
St Paul Ramsey Med Ctr
St Paul, Minnesota, United States, 55101
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New York
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Beth Israel Med Ctr
New York, New York, United States, 10003
Mount Sinai Med Ctr
New York, New York, United States, 10029
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Carolinas Med Ctr
Charlotte, North Carolina, United States, 28203
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Investigators
Study Chair: Havlir D
Study Chair: Richman D
  More Information

Additional Information:
Publications:
Seth A, Markee J, Ap S, Sevin A, Hoering A, Hirsch M, Collier A, Letvin N, McElrath MJ. Alterations in T cell phenotype and antigen-specific cytotoxicity in patients receiving three anti-retroviral agents (ACTG protocol 343). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:132 (abstract no 340)
Havlir DV, Hirsch M, Collier A, Marschner I, Bassett R, Tebas P, Ioannidis J, Richman DD. Randomized trial of indinavir (IDV) vs. zidovudine (ZDV)/lamivudine (3TC) vs IDV/ZDV/3TC maintenance therapy after induction IDV/ZDV/3TC therapy. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:225 (abstract no LB16)
Gulick RM, Mellors J, Havlir D, Eron J, Gonzalez C, McMahon D, Richman D, Valentine F, Rooney J, Jonas L, Meibohm A, Emini E, Chodakewitz J. Potent and sustained antiretroviral activity of indinavir (IDV), zidovudine (ZDV) and lamivudine (3TC). Int Conf AIDS. 1996 Jul 7-12;11(Program Supplement):19 (abstract no ThB931)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001084     History of Changes
Other Study ID Numbers: ACTG 343, 11314
Study First Received: November 2, 1999
Last Updated: May 1, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Prospective Studies
Drug Therapy, Combination
Zidovudine
HIV Protease Inhibitors
Lamivudine
Indinavir
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Indinavir
Lamivudine
Reverse Transcriptase Inhibitors
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014