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.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000770
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine

Resource links provided by NLM:


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

Estimated Enrollment: 400
Study Completion Date: November 1994
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

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Summitt Med Ctr / San Francisco Gen Hosp
Oakland, California, United States, 94609
Highland Gen Hosp / San Francisco Gen Hosp
Oakland, California, United States, 946021018
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
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, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, Indiana
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, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Boston Med Ctr
Boston, Massachusetts, United States, 02118
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, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New York
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Comprehensive Health Care Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
Mount Sinai Med Ctr
New York, New York, United States, 10029
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Beth Israel Med Ctr
New York, New York, United States, 10003
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
Cornell Univ Med Ctr
New York, New York, United States, 10021
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
Wake County Dept of Health
Raleigh, North Carolina, United States, 27610
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
Girard Med Ctr
Philadelphia, Pennsylvania, United States, 191046073
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: D'Aquila R
Study Chair: Hirsch M
  More Information

Additional Information:
Publications:
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)
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)
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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000770     History of Changes
Other Study ID Numbers: ACTG 241, 11218
Study First Received: November 2, 1999
Last Updated: March 30, 2012
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

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

ClinicalTrials.gov processed this record on April 20, 2014