Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
NCT ID: NCT00000838
Last Updated: 2021-11-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
256 participants
INTERVENTIONAL
1998-03-31
Brief Summary
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3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.
Detailed Description
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Patients are randomized to either a ddI limb or d4T limb, then randomized a second time to one of six treatment arms, as follows: ddI alone, d4T alone, 3TC/AZT (on both ddI and d4T limbs), 3TC/ddI, and 3TC/d4T. Treatment is given for 48 weeks. At study week 24, patients on monotherapy will have 3TC added to their regimen (in a blinded fashion).
PER AMENDMENT 10/18/96: A treatment extension phase has been added to the study design in order to allow subjects who complete 48 weeks of therapy to remain on their same blinded treatment until approximately 2 months after the last enrolled subject completes 48 weeks on the study.
Conditions
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Keywords
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Study Design
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TREATMENT
Interventions
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Lamivudine
Stavudine
Zidovudine
Didanosine
Eligibility Criteria
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Inclusion Criteria
Allowed:
* PCP prophylaxis.
Patients must have:
* HIV infection.
* CD4 count 200 - 600 cells/mm3.
* Life expectancy of at least 24 weeks.
* Consent of parent or guardian if less than 18 years old.
Exclusion Criteria
Patients with the following symptoms or conditions are excluded:
* Unexplained temperature \>= 38.5 C for 7 consecutive days within 30 days prior to study entry.
PER AMENDMENT 1/25/96:
* A malignancy that requires systemic chemotherapies other than Kaposi's sarcoma.
Concurrent Medication:
Excluded:
* Concurrent other antiretroviral or immunologic agents.
* Other experimental therapies.
* Systemic corticosteroids (except as adjuvant therapy for acute PCP) and other immunosuppressive drugs.
* Systemic cytotoxic chemotherapy.
* Induction or maintenance with foscarnet or ganciclovir (oral or IV).
Patients with the following prior conditions are excluded:
* History of acute or chronic pancreatitis.
* History of grade 2 or higher peripheral neuropathy.
Prior Medication:
Excluded:
* Antiretrovirals within 90 days prior to study entry.
* More than 7 days total lifetime use of any antiretroviral nucleoside.
12 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Kuritzkes D
Role: STUDY_CHAIR
Johnson V
Role: STUDY_CHAIR
Locations
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Alabama Therapeutics CRS
Birmingham, Alabama, United States
UCLA CARE Center CRS
Los Angeles, California, United States
Stanford CRS
Palo Alto, California, United States
Ucsd, Avrc Crs
San Diego, California, United States
Santa Clara Valley Med. Ctr.
San Jose, California, United States
San Mateo County AIDS Program
San Mateo, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Univ. of Miami AIDS CRS
Miami, Florida, United States
Queens Med. Ctr.
Honolulu, Hawaii, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
Weiss Memorial Hosp.
Chicago, Illinois, United States
Northwestern University CRS
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
NYU Med. Ctr., Dept. of Medicine
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, United States
MetroHealth CRS
Cleveland, Ohio, United States
The Ohio State University Medical Center
Columbus, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Puerto Rico-AIDS CRS
San Juan, , Puerto Rico
Countries
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References
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Marschner I, Betensky RA, Degruttola V, Kuritzkes DR. Biases in the assessment of viral load reduction in HIV clinical trials. Int Conf AIDS. 1998;12:802 (abstract no 42149)
Hill A, Demasi R, Kuhn M. Different analyses give highly variable estimates of HIV-1 RNA undetectability and log reduction in clinical trials. Int Conf AIDS. 1998;12:813-4 (abstract no 42204)
Kuritzkes DR, Marschner IC, Johnson VA, Bassett RL, Eron JJ, Fischl MA, Boone G, Skovronski J, Wood K, Bell DL, Pettinelli CB, Sommadossi JP. A randomized, double-blind, placebo-controlled trial of lamivudine (3TC) in combination with zidovudine (ZDV), stavudine (d4T), or didanosine (ddI) in treatment naive patients. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 1)
Kuritzkes DR, Marschner I, Johnson VA, Bassett R, Eron JJ, Fischl MA, Murphy RL, Fife K, Maenza J, Rosandich ME, Bell D, Wood K, Sommadossi JP, Pettinelli C. Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators. AIDS. 1999 Apr 16;13(6):685-94. doi: 10.1097/00002030-199904160-00009.
Kuritzkes DR, Bassett RL, Hazelwood JD, Barrett H, Rhodes RA, Young RK, Johnson VA; Adult ACTG Protocol 306 370 Teams. Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens. J Acquir Immune Defic Syndr. 2004 May 1;36(1):600-3. doi: 10.1097/00126334-200405010-00008.
Fisher M. Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine. AIDS. 1998;12 Suppl 3:S9-16.
Other Identifiers
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11281
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG 306
Identifier Type: -
Identifier Source: org_study_id