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A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine
This study has been completed.
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000770
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Nevirapine
Drug: Zidovudine
Drug: Didanosine
Phase II

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Didanosine Nevirapine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Double-Blind, Pharmacokinetics Study
Official Title: A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine

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

Estimated Enrollment: 400
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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000770

  Show 44 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: D'Aquila R
Study Chair: Hirsch M
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site
Click here for more information about Didanosine  This link exits the ClinicalTrials.gov site
Click here for more information about Nevirapine  This link exits the ClinicalTrials.gov site

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.

Study ID Numbers: ACTG 241
Study First Received: November 2, 1999
Last Updated: July 31, 2008
ClinicalTrials.gov Identifier: NCT00000770  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Nevirapine

Study placed in the following topic categories:
Virus Diseases
Nevirapine
Sexually Transmitted Diseases, Viral
Didanosine
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009