The Effectiveness of Three Drug Combinations in HIV-Infected Patients Who Have Taken Zidovudine for More Than 12 Weeks
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Stavudine (Drug); Zidovudine (Drug); Didanosine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Havlir D, Study Chair
Richman D, Study Chair
Pollard R, Study Chair
Friedland G, Study Chair
Summary
To compare the effect of stavudine (d4T) alone or with zidovudine (AZT) versus didanosine
(ddI) alone or with AZT on CD4 counts, HIV RNA levels, and viral load in HIV-infected
patients [AS PER AMENDMENT 3/21/97: To compare the effects of d4T alone versus ddI alone
versus AZT plus ddI]. To compare the safety of d4T/AZT. AS PER AMENDMENT 3/21/97: To evaluate
the pharmacokinetic interactions of AZT and d4T both at an extracellular and intracellular
level.
Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these
drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity
profile and demonstrated activity against HIV, offers an additional therapeutic option. It is
reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical
disease progression is directly related to its ability to achieve and sustain viral
suppression; thus, this study measures effects on viral load and CD4 count.
Clinical Details
Official title: A Phase II Randomized Study of the Virologic and Immunologic Effects of d4T Vs Zidovudine Plus d4T Vs Zidovudine Plus Ddl in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and Greater Than 12 Weeks Zidovudine Experience
Study design: Treatment
Detailed description:
Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these
drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity
profile and demonstrated activity against HIV, offers an additional therapeutic option. It is
reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical
disease progression is directly related to its ability to achieve and sustain viral
suppression; thus, this study measures effects on viral load and CD4 count.
Patients are randomized in a blinded fashion to receive AZT or placebo in combination with
open-label d4T or ddI for up to 48 weeks. AS PER AMENDMENT 3/21/97: The study is now composed
of three arms: open-label d4T versus open-label ddI plus blinded AZT placebo versus blinded
AZT plus open-label ddI. Patients originally assigned to the d4T + AZT arm, which was closed
10/96, will be given the option of discontinuing AZT and remaining on d4T monotherapy or
discontinuing all study drugs. In addition, all study participants will be asked to
participate in a pharmacology substudy.
Eligibility
Minimum age: 12 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Required for patients whose CD4 count falls below 200 cells/mm3:
- PCP prophylaxis with TMP/SMX, aerosolized pentamidine, or dapsone.
Allowed:
- Atovaquone, IV pentamidine, trimethoprim-dapsone, clindamycin-primaquine,
trimetrexate, or TMP/SMX for acute PCP.
- Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for
mucosal and esophageal candidiasis.
- Itraconazole.
- Amphotericin B.
- Rifabutin.
- Isoniazid.
- Pyrazinamide.
- Clofazimine.
- Clarithromycin.
- Azithromycin.
- Ethambutol.
- Amikacin.
- Ciprofloxacin.
- Ofloxacin.
- Pyrimethamine.
- Sulfadiazine.
- Clindamycin.
- Ganciclovir.
- G-CSF.
- Acyclovir (up to 1000 mg/day).
- Erythropoietin.
- Antibiotics for bacterial infections.
- Antipyretics.
- Analgesics.
- Antiemetics.
- Rifampin.
Concurrent Treatment:
Allowed:
- Local radiation therapy.
Patients must have:
- HIV infection.
- CD4 count 300-600 cells/mm3.
- More than 12 weeks (was 24 weeks, AMENDED 3/31/96) of total prior AZT ( > 500 mg/day
without serious adverse event). Subjects must be actively taking ZDV for at least 4
continuous weeks up to the time of study entry.
- No prior or current history of AIDS.
- No active opportunistic infection.
- Life expectancy of at least 2 years.
- Consent of patient and parent or guardian if less than 18 years of age.
NOTE:
- Protocol is approved for prisoner enrollment.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Malignancy requiring systemic cytotoxic chemotherapy.
- Serious underlying medical condition other than HIV that would reduce life expectancy
to < 2 years.
Concurrent Medication:
Excluded:
- Antiretrovirals other than study drugs.
- Foscarnet.
Patients with the following prior conditions are excluded:
- Unexplained temperature >= 38. 5 C for 7 days or chronic diarrhea (>= three stools
daily) for 15 days, if occurring within 30 days prior to study entry.
- History of acute or chronic pancreatitis.
- History of grade 2 or higher peripheral neuropathy.
- History of grade 3 or worse intolerance to 500-600 mg/day AZT.
Prior Medication:
Excluded:
(within 30 days prior to study entry)
- Prior ddI, ddC, 3TC or d4T (more than 2 weeks total).
- Non-nucleoside reverse transcriptase inhibitor or protease inhibitor.
- Biologic response modifiers such as interferon and IL-2.
- Other experimental therapy.
Locations and Contacts
San Juan City Hosp, San Juan 009367344, Puerto Rico
Univ of Puerto Rico, San Juan 009365067, Puerto Rico
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Children's Hosp of Los Angeles, Los Angeles, California 90027, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
Mountain States Reg Hemo Ctr / Univ of Colorado, Denver, Colorado 80262, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Rose Med Ctr, Denver, Colorado 80262, United States
Yale Univ / New Haven, New Haven, Connecticut 065102483, United States
Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Illinois Masonic Med Ctr, Chicago, Illinois 606575147, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Division of Inf Diseases/ Indiana Univ Hosp, Indianapolis, Indiana 46202, United States
Tulane Med Ctr Hosp, New Orleans, Louisiana 70112, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
King's County Hosp Ctr / Pediatrics, Brooklyn, New York 11203, United States
SUNY - Brooklyn, Brooklyn, New York 11203, United States
SUNY / State Univ of New York, Syracuse, New York 13210, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Harlem Hosp Ctr, New York, New York 10037, United States
Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States
Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp, Bronx, New York 10461, United States
Duke Univ Med Ctr, Durham, North Carolina 277103499, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ Texas Health Science Ctr / Univ Texas Med School, Houston, Texas 77030, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Univ of Washington, Seattle, Washington 981224304, United States
Great Lakes Hemophilia Foundation, Wauwatosa, Wisconsin 532130127, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Didanosine Click here for more information about Stavudine
Related publications: [No authors listed] d4T+AZT--unexpected CD4 drop seen in study. AIDS Treat News. 1996 Dec 20;(No 261):1. No abstract available. Shaefer M, Hardy WD, Shaker-Irwin L, Williams V, Maude C, Thommes J, Graham N. HIV viral load response in subjects switched from zidovudine (ZDV)-containing to stavudine (D4T)-containing regimens in the Pacific Oaks Population Study (POPS). Int Conf AIDS. 1998;12:57 (abstract no 12228) Havlir DV, Friedland G, Pollard R, Tierney C, Smeaton L, Fox L, Richman DD. Combination zidovudine (ZDV) and stavudine (d4T) therapy versus other nucleosides: report of two randomized trials (ACTG 290 and 298). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 2) Cadman J. 2, 4, 6, 8, who's afraid to phosphorylate? GMHC Treat Issues. 1998 Feb;12(2):6-8. No abstract available. Havlir DV, Tierney C, Friedland GH, Pollard RB, Smeaton L, Sommadossi JP, Fox L, Kessler H, Fife KH, Richman DD. In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis. 2000 Jul;182(1):321-5. Sommadossi JP, Zhou XJ, Moore J, Havlir DV, Friedland G, Tierney C, Smeaton L, Fox L, Richman D, Pollard R. Impairment of stavudine (d4T) phosphorylation in patients receiving a combination of zidovudine (ZDV) and d4T (ACTG 290). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 3)
Last updated: June 23, 2005
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