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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000770
• Other study ID #: ACTG 241
• Secondary ID: 11218
• Status: Completed
• Phase: Phase 2
• Est. completion date: November 1994

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: November 1994
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Nevirapine

• Zidovudine

• Didanosine

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Bristol-Myers Squibb, Glaxo Wellcome

Country where clinical trial is conducted

United States, 

References & 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. — View 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. — View 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)

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. — View 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

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. — View 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)

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)

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