A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine

NCT00000770 | Completed Phase 2

• 2 other identifiers: ACTG 24111218
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 44

Brief 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.

Conditions

HIV Infections

Keywords

Didanosine; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Zidovudine; Nevirapine

Interventions

Nevirapine DRUG

Zidovudine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• Glaxo Wellcome: collaborator

Study Sites (44)

Univ of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, 900331079, United States

Location

Highland Gen Hosp / San Francisco Gen Hosp

Oakland, California, 946021018, United States

Location

Summitt Med Ctr / San Francisco Gen Hosp

Oakland, California, 94609, United States

Location

Univ of California / San Diego Treatment Ctr

San Diego, California, 921036325, United States

Location

San Francisco AIDS Clinic / San Francisco Gen Hosp

San Francisco, California, 941102859, United States

Location

San Francisco Gen Hosp

San Francisco, California, 941102859, United States

Location

Univ of Colorado Health Sciences Ctr

Denver, Colorado, 80262, United States

Location

Univ of Miami School of Medicine

Miami, Florida, 331361013, United States

Location

Northwestern Univ Med School

Chicago, Illinois, 60611, United States

Location

Cook County Hosp

Chicago, Illinois, 60612, United States

Location

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, 60612, United States

Location

Indiana Univ Hosp

Indianapolis, Indiana, 462025250, United States

Location

Univ of Iowa Hosp and Clinic

Iowa City, Iowa, 52242, United States

Location

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, 02114, United States

Location

Boston Med Ctr

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - West Campus

Boston, Massachusetts, 02215, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Hennepin County Med Clinic

Minneapolis, Minnesota, 55415, United States

Location

Univ of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St Paul Ramsey Med Ctr

Saint Paul, Minnesota, 55101, United States

Location

Univ of Nebraska Med Ctr

Omaha, Nebraska, 681985130, United States

Location

City Hosp Ctr at Elmhurst / Mount Sinai Hosp

Elmhurst, New York, 11373, United States

Location

Beth Israel Med Ctr

New York, New York, 10003, United States

Location

Saint Clare's Hosp and Health Ctr

New York, New York, 10019, United States

Location

Cornell Univ Med Ctr

New York, New York, 10021, United States

Location

Mem Sloan - Kettering Cancer Ctr

New York, New York, 10021, United States

Location

Mount Sinai Med Ctr

New York, New York, 10029, United States

Location

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, 10461, United States

Location

Comprehensive Health Care Ctr / Bronx Municipal Hosp

The Bronx, New York, 10461, United States

Location

Montefiore Drug Treatment Ctr / Bronx Municipal Hosp

The Bronx, New York, 10461, United States

Location

Montefiore Family Health Ctr / Bronx Municipal Hosp

The Bronx, New York, 10461, United States

Location

Samaritan Village Inc / Bronx Municipal Hosp

The Bronx, New York, 10461, United States

Location

Jack Weiler Hosp / Bronx Municipal Hosp

The Bronx, New York, 10465, United States

Location

Montefiore Med Ctr / Bronx Municipal Hosp

The Bronx, New York, 10467, United States

Location

North Central Bronx Hosp / Bronx Municipal Hosp

The Bronx, New York, 10467, United States

Location

Univ of North Carolina

Chapel Hill, North Carolina, 275997215, United States

Location

Carolinas Med Ctr

Charlotte, North Carolina, 28203, United States

Location

Moses H Cone Memorial Hosp

Greensboro, North Carolina, 27401, United States

Location

Wake County Dept of Health

Raleigh, North Carolina, 27610, United States

Location

Univ of Cincinnati

Cincinnati, Ohio, 452670405, United States

Location

Girard Med Ctr

Philadelphia, Pennsylvania, 191046073, United States

Location

Univ of Pennsylvania at Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson Univ Hosp

Philadelphia, Pennsylvania, 191075098, United States

Location

Related Publications (10)

• 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. doi: 10.7326/0003-4819-124-12-199606150-00001.

  PMID: 8633815 BACKGROUND

• 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)

  BACKGROUND

• 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)

  BACKGROUND

• 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. doi: 10.1128/jcm.33.1.246-247.1995.

  PMID: 7699053 BACKGROUND

• 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. doi: 10.1086/515307.

  PMID: 9607832 BACKGROUND

• Virus sidesteps convergent therapy. GMHC Treat Issues. 1995 Jan;9(1):6.

  PMID: 11367380 BACKGROUND

• 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)

  BACKGROUND

• 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. doi: 10.1128/AAC.43.1.121.

  PMID: 9869576 BACKGROUND

• 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

  BACKGROUND

• 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. doi: 10.7326/0003-4819-126-12-199706150-00001.

  PMID: 9182469 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Nevirapine; Zidovudine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• D'Aquila R

  STUDY CHAIR

• Hirsch M

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: November 1, 1994
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (44)