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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,292
- 试验地点
- 96
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Concurrent Medication:
- •PCP prophylaxis.
- •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:
- •Radiation therapy for cutaneous Kaposi's sarcoma.
- •Acupuncture.
- •Patients must have:
- •Documented HIV infection.
- •CD4 count <= 50 cells/mm
- •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).
- •Patients who withdrew from protocol ACTG 193 therapy prior to activation of ACTG 193A are not eligible.
排除标准
- •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:
- •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:
- •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:
- •More than 4 units of blood in a 30-day period.
- •Active alcohol or drug abuse.