A Multicenter, Double Blind, Comparative Study of Zidovudine Alone Versus Zidovudine and Acyclovir as Treatment for HIV-Infected Patients With CD4+ Counts Less Than 200 Cells/mm3
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Zidovudine (Drug); Acyclovir (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Collier AC, Study Chair
Hirsch M, Study Chair
Corey L, Study Chair
Summary
Original design: The study's purpose is to compare the effects of zidovudine (AZT) alone to
the combination of AZT and acyclovir (ACV) to determine if AZT/ACV is associated with a lower
death rate and fewer AIDS related opportunistic infections compared to AZT alone, and to
investigate the effect of these treatment plans on cytomegalovirus (CMV) and Epstein-Barr
virus (EBV) infections. The study evaluates two doses of AZT used alone versus two doses of
AZT combined with ACV. Per 12/11/92 amendment: Another antiretroviral agent may be
substituted for AZT.
AZT has been shown to increase the life span of patients with AIDS or advanced AIDS related
complex and patients being treated for Pneumocystis carinii pneumonia. Drugs that increase
the effectiveness of AZT against HIV may also decrease the need for high doses of AZT. This
might reduce some of the negative effects of AZT while not reducing the positive effects.
Clinical Details
Official title: A Multicenter, Double Blind, Comparative Study of Zidovudine Alone Versus Zidovudine and Acyclovir as Treatment for HIV-Infected Patients With CD4+ Counts Less Than 200 Cells/mm3
Study design: Treatment, Parallel Assignment
Detailed description:
AZT has been shown to increase the life span of patients with AIDS or advanced AIDS related
complex and patients being treated for Pneumocystis carinii pneumonia. Drugs that increase
the effectiveness of AZT against HIV may also decrease the need for high doses of AZT. This
might reduce some of the negative effects of AZT while not reducing the positive effects.
AMENDED: Patients are randomly assigned to one of two treatment regimens. They receive AZT
(or other antiretroviral agent) with or without ACV. Treatment Plan 1: AZT along with placebo
at the same time. Treatment Plan 2: AZT and ACV. Therapy is for 104 weeks with an optional
extension of 24 weeks or until the end of the study whichever comes first. The maximum
duration of therapy for any patient will be 128 weeks. Medication is dispensed on a biweekly
basis for the first 4 weeks, then every other month for the remainder of the study. Original
design: Patients are randomly assigned to one of four treatment plans to receive AZT alone
or AZT and ACV. Medications are given every 4 hours (q4h) orally (PO) while awake (WA). A
total of 5 doses/day are given. The per dose schedule for the four plans are: Treatment plan
1: AZT plus placebo (an inactive medication) substituting for ACV. Treatment plan 2: AZT and
AZT placebo along with an ACV placebo. Treatment plan 3: AZT and ACV. Treatment plan 4: AZT
and AZT placebo and ACV.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Allowed:
- Methadone maintenance. Therapies available through expanded access or treatment IND
programs unless specifically excluded.
- Allowed within 30 days of study entry:
- Systemic steroids only if given for treatment of Pneumocystis carinii pneumonia.
- Recommended:
- PCP prophylaxis.
Patient must have:
- Recovered from first episode of histologically proven Pneumocystis carinii pneumonia
(PCP) or microbiologically proven AIDS-defining opportunistic infection as defined in
Centers for Disease Control HIV classification group IV.
- C-1.
- Study entry must be within 120 days of AIDS-defining diagnosis.
- Written documentation of positive antibody to HIV by any federally licensed ELISA test
kit. This test should be confirmed by another method, for example, Western blot,
radioimmunoassay (RIA), HIV culture.
- Patients cannot be transfusion dependent (requiring blood transfusion more than once
per month). The last transfusion must be > 2 weeks before entry.
- AMENDED 90-08-27 to include HIV positive patients with CD4+ count < 200 cells/mm3.
Prior Medication:
Allowed:
- Zidovudine (AZT) for < 365 days prior to study entry.
Exclusion Criteria
Co-existing Condition:
Patients with the following are excluded:
- Symptomatic visceral or progressive Kaposi's sarcoma (KS) (defined by > 10 new lesions
in the 30 days prior to entry).
- Other concurrent neoplasms other than basal cell carcinoma of skin (patients who have
been in complete remission for 1 year for a malignancy may be enrolled).
- Malabsorption as defined by persistent diarrhea > 6 stools/day for > 4 weeks. Patients
whose sole AIDS-defining condition is constitutional disease as defined in CDC's HIV
group IV-A or neurologic disease as defined in CDC's HIV group IV-B or AIDS-associated
malignancies as defined in CDC's HIV group IV-C.
Concurrent Medication:
Excluded:
- Acyclovir (ACV) prophylaxis or frequent (> once per month) repeated courses of ACV
therapy for herpes simplex virus infection.
- Any concomitant medicine unless required.
- Systemic therapy/prophylaxis/maintenance for AIDS-defining opportunistic infection
other than prophylaxis for Pneumocystis carinii pneumonia (PCP).
- Acetaminophen for > 72 hours. Cimetidine.
- Flurazepam.
- Indomethacin.
- Ranitidine.
- Probenecid (if receiving AZT).
- Rifampin.
- Rifampin-related drugs.
Patients with the following are excluded:
- Active opportunistic infections.
- Symptomatic visceral or progressive Kaposi's sarcoma (KS) (defined by > 10 new lesions
in the 30 days prior to entry).
- Other concurrent neoplasms other than basal cell carcinoma of skin (patients who have
been in complete remission for 1 year for a malignancy may be enrolled).
- Malabsorption as defined by persistent diarrhea > 6 stools/day for > 4 weeks.
- Patients whose sole AIDS-defining condition is constitutional disease as defined in
CDC's HIV group IV-A or neurologic disease as defined in CDC's HIV group IV-B or
AIDS-associated malignancies as defined in CDC's HIV group IV-C.
Prior Medication:
Excluded:
- Zidovudine (AZT) for > 365 days prior to study entry.
- Excluded within 14 days of study entry:
- Systemic acyclovir (ACV) therapy.
- Excluded within 30 days of study entry:
- Antiretroviral therapy (other than AZT per above).
- Immunomodulating agents.
- Biologic response modifiers.
Excluded within 60 days of study entry:
- Ribavirin.
Prior Treatment:
Excluded within 30 days of study entry:
- Cytotoxic chemotherapy or radiation therapy for Kaposi's sarcoma.
Active substance abuse that would impair compliance with study procedure.
Locations and Contacts
George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States
Charity Hosp / Tulane Univ Med School, New Orleans, Louisiana 70112, United States
Louisiana State Univ Med Ctr / Tulane Med School, New Orleans, Louisiana 70112, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
Univ of Missouri at Kansas City School of Medicine, Kansas City, Missouri 64108, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 68198, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Wake Med Ctr / Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Bowman Gray School of Medicine / Wake Forest Univ, Winston Salem, North Carolina 27103, United States
Vanderbilt Univ Hosp, Nashville, Tennessee 372322605, United States
Retrovir Study Ctr, Houston, Texas 77004, United States
Community Clinic for AIDS Research, Dallas, Texas 75219, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Acyclovir
Related publications: Collier AC, Schoenfeld DA, Bourland D, Hirsch M, Davis LG, Corey L. Prospective comparative study of acyclovir (ACV) and zidovudine (ZDV) versus ZDV alone in patients with AIDS. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2;125 Ioannidis JP, Collier AC, Cooper DA, Corey L, Fiddian AP, Gazzard BG, Griffiths PD, Contopoulos-Ioannidis DG, Lau J, Pavia AT, Saag MS, Spruance SL, Youle MS. Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis. 1998 Aug;178(2):349-59.
Last updated: June 23, 2005
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