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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nevirapine
Zidovudine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine, Nevirapine

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Univ of Alabama at Birmingham
  • Univ of Southern California / LA County USC Med Ctr
  • Highland Gen Hosp / San Francisco Gen Hosp
  • Summitt Med Ctr / San Francisco Gen Hosp
  • Univ of California / San Diego Treatment Ctr
  • San Francisco AIDS Clinic / San Francisco Gen Hosp
  • San Francisco Gen Hosp
  • Univ of Colorado Health Sciences Ctr
  • Univ of Miami School of Medicine
  • Northwestern Univ Med School
  • Cook County Hosp
  • Rush Presbyterian - Saint Luke's Med Ctr
  • Indiana Univ Hosp
  • Univ of Iowa Hosp and Clinic
  • Harvard (Massachusetts Gen Hosp)
  • Boston Med Ctr
  • Beth Israel Deaconess - West Campus
  • Beth Israel Deaconess Med Ctr
  • Hennepin County Med Clinic
  • Univ of Minnesota
  • St Paul Ramsey Med Ctr
  • Univ of Nebraska Med Ctr
  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
  • Comprehensive Health Care Ctr / Bronx Municipal Hosp
  • Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
  • Montefiore Family Health Ctr / Bronx Municipal Hosp
  • Samaritan Village Inc / Bronx Municipal Hosp
  • Jack Weiler Hosp / Bronx Municipal Hosp
  • Montefiore Med Ctr / Bronx Municipal Hosp
  • North Central Bronx Hosp / Bronx Municipal Hosp
  • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
  • Beth Israel Med Ctr
  • Saint Clare's Hosp and Health Ctr
  • Cornell Univ Med Ctr
  • Mem Sloan - Kettering Cancer Ctr
  • Mount Sinai Med Ctr
  • Univ of North Carolina
  • Carolinas Med Ctr
  • Moses H Cone Memorial Hosp
  • Wake County Dept of Health
  • Univ of Cincinnati
  • Girard Med Ctr
  • Univ of Pennsylvania at Philadelphia
  • Thomas Jefferson Univ Hosp

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00000770
Brief Title
A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine
Official Title
A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
November 1994 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine, Nevirapine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
Double
Enrollment
400 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Nevirapine
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
D'Aquila R
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hirsch M
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Univ of Southern California / LA County USC Med Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
900331079
Country
United States
Facility Name
Highland Gen Hosp / San Francisco Gen Hosp
City
Oakland
State/Province
California
ZIP/Postal Code
946021018
Country
United States
Facility Name
Summitt Med Ctr / San Francisco Gen Hosp
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Univ of California / San Diego Treatment Ctr
City
San Diego
State/Province
California
ZIP/Postal Code
921036325
Country
United States
Facility Name
San Francisco AIDS Clinic / San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Univ of Colorado Health Sciences Ctr
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Univ of Miami School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Northwestern Univ Med School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Presbyterian - Saint Luke's Med Ctr
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Univ of Iowa Hosp and Clinic
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Harvard (Massachusetts Gen Hosp)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Med Ctr
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - West Campus
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Beth Israel Deaconess Med Ctr
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hennepin County Med Clinic
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Univ of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St Paul Ramsey Med Ctr
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Univ of Nebraska Med Ctr
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
681985130
Country
United States
Facility Name
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Comprehensive Health Care Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Family Health Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Samaritan Village Inc / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Jack Weiler Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10465
Country
United States
Facility Name
Montefiore Med Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
North Central Bronx Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
City
Elmhurst
State/Province
New York
ZIP/Postal Code
11373
Country
United States
Facility Name
Beth Israel Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Saint Clare's Hosp and Health Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Cornell Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mem Sloan - Kettering Cancer Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Carolinas Med Ctr
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Moses H Cone Memorial Hosp
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
Wake County Dept of Health
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27610
Country
United States
Facility Name
Univ of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Girard Med Ctr
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191046073
Country
United States
Facility Name
Univ of Pennsylvania at Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson Univ Hosp
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191075098
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8633815
Citation
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.
Results Reference
background
Citation
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)
Results Reference
background
Citation
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)
Results Reference
background
PubMed Identifier
7699053
Citation
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.
Results Reference
background
PubMed Identifier
9607832
Citation
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.
Results Reference
background
PubMed Identifier
11367380
Citation
Virus sidesteps convergent therapy. GMHC Treat Issues. 1995 Jan;9(1):6.
Results Reference
background
Citation
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)
Results Reference
background
PubMed Identifier
9869576
Citation
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.
Results Reference
background
Citation
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
Results Reference
background
PubMed Identifier
9182469
Citation
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.
Results Reference
background

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

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