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A Randomized, Double-Blind, Four-Arm Study Comparing Combination Nucleoside, Alternating Nucleoside, and Triple-Drug Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3)

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:
NCT00000781
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012

November 2, 1999
March 30, 2012
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Complete list of historical versions of study NCT00000781 on ClinicalTrials.gov Archive Site
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A Randomized, Double-Blind, Four-Arm Study Comparing Combination Nucleoside, Alternating Nucleoside, and Triple-Drug Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3)
A Randomized, Double-Blind, Four-Arm Study Comparing Combination Nucleoside, Alternating Nucleoside, and Triple-Drug Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3)

To determine the relative clinical efficacy of zidovudine ( AZT ) plus didanosine (ddI), AZT plus zalcitabine ( ddC ), AZT alternating monthly with ddI, and AZT/ddI plus nevirapine in HIV-infected patients with advanced disease.

The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.

The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.

Patients are randomized to receive either AZT/ddC, AZT/ddI, AZT alternating monthly with ddI, or AZT/ddI/nevirapine. Patients are evaluated at week 0 and every 4 weeks thereafter for 2 years. Pharmacologic, virologic, and macroneurologic substudies will be conducted. Patients who are already enrolled on protocol ACTG 193 will be given the option of continuing on their originally assigned ACTG 193 therapy for an additional 6 months or undergoing re-randomization to one of the four treatment arms on ACTG 193A.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Masking: Double-Blind
Primary Purpose: Treatment
HIV Infections
  • Drug: Nevirapine
  • Drug: Zidovudine
  • Drug: Zalcitabine
  • Drug: Didanosine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1292
September 1996
Not Provided

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis.

Allowed:

  • Erythropoietin maintenance.
  • G-CSF and GM-CSF.
  • Prophylaxis for Mycobacterium avium intracellulare.
  • Antifungal prophylaxis or treatment with specific drugs.
  • Maintenance therapy for opportunistic infection.
  • Over-the-counter medications or alternative therapies such as vitamins and herbs.
  • Antibiotics as clinically indicated.
  • Steroids for < 21 days for acute problems.
  • Antipyretics, analgesics, allergy medication, antidepressants, sleep medications, oral contraceptives, or other appropriate medications.

Concurrent Treatment:

Allowed:

  • Radiation therapy for cutaneous Kaposi's sarcoma.
  • Acupuncture.

Patients must have:

  • Documented HIV infection.
  • CD4 count <= 50 cells/mm3.
  • Either no prior nucleoside therapy OR a history of prior nucleoside therapy in the absence of high-grade intolerance.
  • Life expectancy of at least 6 months.
  • Consent of parent or guardian if < 18 years of age.
  • Normal chest x-ray at baseline or within 6 months prior to study entry in the absence of new pulmonary or cardiac symptoms (per 12/28/94 amendment).

NOTE:

  • Patients who withdrew from protocol ACTG 193 therapy prior to activation of ACTG 193A are not eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Abnormal baseline chest x-ray.
  • New pulmonary or cardiac symptoms.
  • Psychological or emotional problems sufficient to prevent compliance with study medication.

Concurrent Medication:

Excluded:

  • Systemic chemotherapy for malignancy.
  • Acute or induction therapy for opportunistic infection.
  • Antiretroviral drugs other than study drugs.
  • Biological response modifiers.
  • Erythromycin, phenytoin, phenobarbital, warfarin, or coumadin.

Patients with the following prior conditions are excluded:

  • History of recurrent grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.
  • Evidence of active pulmonary disease within 6 months prior to study entry.
  • History of grade 3 or worse peripheral neuropathy.
  • History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

  • Prior nevirapine.

Excluded within 7 days prior to study entry:

  • Acute therapy for opportunistic infection (maintenance therapy is permitted).
  • Acute systemic therapy for a nonopportunistic infection or other medical condition.
  • Antiretroviral drugs other than AZT, ddI, or ddC.
  • Biological response modifiers.
  • d4T therapy.
  • Nucleosides other than those used in the study.
  • Antibiotics containing clavulanate potassium.

Prior Treatment:

Excluded:

  • More than 4 units of blood in a 30-day period.

Active alcohol or drug abuse.

Both
13 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00000781
ACTG 193A, 11169
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
  • Bristol-Myers Squibb
  • Glaxo Wellcome
Study Chair: Henry WK
Study Chair: Kahn JO
Study Chair: Balfour HH
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP