Clinical trial NCT00002324: The Safety and Effectiveness of Nevirapine and Zidovudine, Given Separately and Together, in HIV-1 Infected Patients Who Have No Symptoms of the Disease
Official title: A Multi-Center, Placebo-Controlled, Double-Blind, Randomized Trial Comparing the Activity, Safety, and Tolerance of 1) 400 Mg Nevirapine in Combination With 500-600 Mg Zidovudine Versus Zidovudine Alone in Asymptomatic HIV-1 Infected Patients With 3-24 Months of Prior Zidovudine Therapy and 200-500 CD4 Cells/mm3 and 2) 400 Mg Nevirapine Versus Nevirapine Placebo in Asymptomatic HIV-1 Nucleoside Naive Patients With 200-500 CD4 Cells/mm3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
AIDS-Related Complex
Zidovudine
Nevirapine
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 250
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: PRIMARY: To compare the effect of nevirapine versus placebo alone or in combination with zidovudine (AZT) on CD4 T-cell count and percentage after 3 and 6 months of treatment. To evaluate the safety and tolerance of nevirapine alone or in combination with AZT.

SECONDARY: To compare the effects of the various treatment combinations on virologic and immunologic markers.

Detailed description: In Part I, patients who have had prior AZT therapy receive either nevirapine or placebo in combination with AZT. In Part II, patients who are nucleoside naive receive either nevirapine or matching placebo. After 6 months, patients receive open-label nevirapine.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* PCP prophylaxis (trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine), at the discretion of the investigator.
* Antifungal prophylaxis with oral fluconazole or ketoconazole.
* Antiviral prophylaxis for herpes simplex virus with \<= 1000 mg/day oral acyclovir.
* Dilantin for prevention and treatment of seizures.

Patients must have:

* Asymptomatic HIV-1 infection, with positive serum antibody to HIV-1 as determined by ELISA or Western blot.
* CD4 count 200-500 cells/mm3 within 4-28 days prior to study entry.
* No conditions indicative of AIDS.
* None of the constitutional symptoms that are specifically excluded.
* Prior AZT for 3-24 months (amended 04/04/94) immediately prior to study entry (Part I) OR no prior AZT (Part II).
* Consent of parent or guardian if less than 18 years of age.

NOTE:

* Co-enrollment in a protocol involving another investigational drug or biologic is not permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Malignancy other than limited cutaneous basal cell carcinoma.
* Psychiatric condition sufficient to impair compliance with protocol requirements.

Concurrent Medication:

Excluded:

* Investigational drugs other than study drugs.
* Systemic glucocorticoids and steroid hormones.
* Dicumarol, warfarin, and other anticoagulant medications.
* Cimetidine.
* Tolbutamide.
* Doxycycline.
* Chloramphenicol.
* Phenobarbital and other barbiturates.
* Foscarnet.
* Erythromycin.
* Amoxicillin-clavulanate (Augmentin).
* Ticarcillin clavulanate (Timentin).
* Biologic response modifiers (alpha interferon, IL-2, immune modulators).

Patients with the following condition are excluded:

History of other clinically important disease (i.e., one that precludes participation in the study).

Prior Medication:

Excluded:

* Antiretroviral medications other than AZT.

Excluded within 4 weeks prior to study entry:

* Immunosuppressive or cytotoxic drugs or other experimental drugs.
* Systemic glucocorticoids and steroid hormones.
* Dicumarol, warfarin, and other anticoagulant medications.
* Cimetidine.
* Tolbutamide.
* Doxycycline.
* Chloramphenicol.
* Phenobarbital and other barbiturates.
* Foscarnet.
* Erythromycin.
* Amoxicillin-clavulanate (Augmentin).
* Ticarcillin clavulanate (Timentin).
* Biologic response modifiers (alpha interferon, IL-2, immune modulators).

Required (for patients in Part I):

* Prior AZT at 500-600 mg daily for at least 3 months but not more than 24 months immediately prior to study entry.

Chronic use of alcohol or drugs sufficient to impair compliance with protocol requirements.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Treatment Ctr
state: California
city: San Francisco
country: United States
facility: Saint Francis Mem Hosp
state: California
city: Wilmington
country: United States
facility: Wilmington Hosp
state: Delaware
city: Coral Gables
country: United States
facility: Community Research Initiative of South Florida
state: Florida
city: Maitland
country: United States
facility: Goodgame Med Group
state: Florida
city: Wichita
country: United States
facility: Univ of Kansas School of Medicine
state: Kansas
city: Lexington
country: United States
facility: Chandler Med Ctr
state: Kentucky
city: Kansas City
country: United States
facility: Kansas City AIDS Research Consortium
state: Missouri
city: New York
country: United States
facility: Community Research Initiative on AIDS
state: New York
city: Toledo
country: United States
facility: Med College of Ohio
state: Ohio
city: Tulsa
country: United States
facility: Associates Med and Mental Health
state: Oklahoma
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Columbia
country: United States
facility: Dr Alfred F Burnside Jr
state: South Carolina
city: Dallas
country: United States
facility: Nelson-Tebedo Community Clinic
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Network
state: Texas
city: Salt Lake City
country: United States
facility: Univ of Utah School of Medicine
state: Utah
city: Annandale
country: United States
facility: Infectious Disease Physicians Inc
state: Virginia
city: Richmond
country: United States
facility: Richmond AIDS Consortium
state: Virginia
Study officials:
References:
citation: Pollard R . Surrogate marker response to NVP/ZDV or ZDV in a blinded clinical trial: correlation to changes in HIV isolate phenotypic susceptibility to NVP and ZDV. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:113