A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine
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: Nevirapine (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):
D'Aquila R, Study Chair
Hirsch M, Study Chair
Summary
To assess the safety and toxicity of zidovudine (AZT)/didanosine (ddI) versus AZT/ddI
combined with nevirapine in HIV-infected patients, and to obtain preliminary anti-HIV
activity data using immunologic and virologic markers.
Previous in vitro studies suggest that HIV that has already developed resistance to AZT and
ddI is less able to develop resistance to nevirapine, a non-nucleoside reverse transcriptase
inhibitor. Thus, convergent combination therapy with these three drugs in HIV-infected
patients may prove more effective.
Clinical Details
Official title: A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine
Study design: Treatment, Double-Blind, Pharmacokinetics Study
Detailed description:
Previous in vitro studies suggest that HIV that has already developed resistance to AZT and
ddI is less able to develop resistance to nevirapine, a non-nucleoside reverse transcriptase
inhibitor. Thus, convergent combination therapy with these three drugs in HIV-infected
patients may prove more effective.
Patients are randomized to receive AZT/ddI plus either nevirapine or placebo daily for 48
weeks, with possible extension for at least 12 weeks. At eight participating sites, ACTG 808
and 809 will be conducted as virologic and pharmacokinetic substudies.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Required:
- PCP prophylaxis for patients with CD4 count < 200 cells/mm3 or a prior history of
PCP.
Allowed:
- Trimethoprim with sulfamethoxazole or dapsone, intravenous pentamidine, atovaquone,
primaquine-clindamycin or trimetrexate for acute PCP.
- Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for
treatment of mucosal and esophageal candidiasis.
- Prophylaxis or therapy for opportunistic infections, as indicated, with other
medications such as itraconazole, isoniazid, pyrazinamide, clofazimine,
clarithromycin, azithromycin, ethambutol, amikacin, ciprofloxacin, ofloxacin,
pyrimethamine, sulfadiazine, and clindamycin.
- Maintenance therapy for opportunistic infections as long as patients have been on a
stable dosage regimen for 1 month prior to study entry.
- Ganciclovir for CMV retinitis or gastrointestinal disease as long as patients have
been on a stable dose for at least 1 month prior to study entry with no grade 3 or 4
neutropenia or dependence on G-CSF.
- Acyclovir (<= 1000 mg/day) for maintenance of herpes simplex virus infections.
- Erythropoietin or G-CSF if clinically indicated.
- Antibiotics for bacterial infections unless specifically excluded.
- Rifampin or rifabutin.
- Symptomatic treatments such as antipyretics, analgesics, and antiemetics.
Concurrent Treatment:
Allowed:
- Local radiation therapy.
Prior Medication: Required:
- At least 6 months of prior cumulative nucleoside therapy with AZT, ddI, or ddC, given
as monotherapy or in combination.
Patients must have:
- Prior or current documentation of HIV seropositivity by ELISA confirmed by Western
blot, positive HIV antigen, or positive HIV culture, or a second antibody test by a
method other than ELISA.
- CD4 count <= 350 cells/mm3.
- Prior cumulative nucleoside therapy of >= 6 months.
- Consent of parent or guardian if less than 18 years of age.
Exclusion Criteria
Concurrent Medication:
Excluded:
- Antiretroviral therapies other than study medications.
- Systemic corticosteroids given consecutively for > 21 days.
- Induction or maintenance with foscarnet.
- Systemic cytotoxic chemotherapy for a malignancy.
- Erythromycin.
- Coumadin/warfarin.
- Phenytoin or phenobarbital.
- Amoxicillin/clavulanate acid (Augmentin) or ticarcillin/clavulanate acid (Timentin).
Patients with the following prior conditions are excluded:
- History of pancreatitis.
- History of intolerance to 500 or 600 mg/day AZT or to 400 mg/day ddI tablets or 500
mg/day ddI sachets.
- History of grade 2 or worse peripheral neuropathy.
Prior Medication:
Excluded at any time:
Prior non-nucleoside reverse transcriptase inhibitors (NVP; L697,611; TIBO; atevirdine).
Excluded within 14 days prior to study entry:
- Acute treatment for a serious infection or any opportunistic infection.
- Biologic response modifiers such as interferon and IL-2.
- Erythromycin.
- Coumadin/warfarin.
- Phenytoin or phenobarbital.
- Ticarcillin/clavulanate acid (Timentin) or amoxicillin/clavulanate acid (Augmentin).
Locations and Contacts
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco, California 941102859, United States
Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Highland Gen Hosp / San Francisco Gen Hosp, Oakland, California 946021018, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, 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
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States
Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Samaritan Village Inc / Bronx Municipal Hosp, Bronx, New York 10461, United States
Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Cornell Univ Med Ctr, New York, New York 10021, 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
Beth Israel Med Ctr, New York, New York 10003, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States
Saint Clare's Hosp and Health Ctr, New York, New York 10019, United States
North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States
Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Carolinas Med Ctr, Charlotte, North Carolina 28203, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Wake County Dept of Health, Raleigh, North Carolina 27610, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States
Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States
Girard Med Ctr, Philadelphia, Pennsylvania 191046073, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Didanosine Click here for more information about Nevirapine
Related publications: D'Aquila RT, Hughes MD, Johnson VA, Fischl MA, Sommadossi JP, Liou SH, Timpone J, Myers M, Basgoz N, Niu M, Hirsch MS. Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators. Ann Intern Med. 1996 Jun 15;124(12):1019-30. Dusek A, Hall D, Lamson M, Myers M. Once-daily dosing of nevirapine: a retrospective, cross-study analysis. Int Conf AIDS. 1998;12:85 (abstract no 12360) Leigh Brown AJ, D'Aquila RT, Johnson VA, Kuritzkes DR, Richman DD. Baseline sequence clusters predict response to combination therapy in ACTG 241. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:211 (abstract no 704) Fiscus SA, Welles SL, Spector SA, Lathey JL. Length of incubation time for human immunodeficiency virus cultures. J Clin Microbiol. 1995 Jan;33(1):246-7. D'Aquila RT, Sutton L, Savara A, Hughes MD, Johnson VA. CCR5/delta(ccr5) heterozygosity: a selective pressure for the syncytium-inducing human immunodeficiency virus type 1 phenotype. NIAID AIDS Clinical Trials Group Protocol 241 Virology Team. J Infect Dis. 1998 Jun;177(6):1549-53. [No authors listed] Virus sidesteps convergent therapy. GMHC Treat Issues. 1995 Jan;9(1):6. No abstract available. Precious H, Leigh Brown AJ, Gunthard HF, Wong JK, D'Aquila RT, Johnson VA, Kuritzkes DR, Richman DD. A multiple regression model predicting response to combination therapy from baseline sequence data identifies amino acid sites not previously associated with resistance. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:69 (abstract no 14) Zhou XJ, Sheiner LB, D'Aquila RT, Hughes MD, Hirsch MS, Fischl MA, Johnson VA, Myers M, Sommadossi JP. Population pharmacokinetics of nevirapine, zidovudine, and didanosine in human immunodeficiency virus-infected patients. The National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators. Antimicrob Agents Chemother. 1999 Jan;43(1):121-8. Hall D, Robinson P, Cort S, Kohlbrenner V, Leitz G, Myers M. Duration of effect of nevirapine (NVP), a cross-trial analysis of three controlled studies. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:79 Hughes MD, Johnson VA, Hirsch MS, Bremer JW, Elbeik T, Erice A, Kuritzkes DR, Scott WA, Spector SA, Basgoz N, Fischl MA, D'Aquila RT. Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team. Ann Intern Med. 1997 Jun 15;126(12):929-38.
Last updated: June 23, 2005
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