Clinical trial NCT00000754: A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3
Official title: A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Zalcitabine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Interferon-alpha
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Hoffmann-La Roche
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine the safety and efficacy of two doses of interferon alfa-2a ( IFN alfa-2a ) in combination with zidovudine ( AZT )/zalcitabine ( ddC ) versus AZT/ddC only in patients with HIV infection and CD4 count \< 400 cells/mm3.

AZT and ddC inhibit HIV by acting as reverse transcriptase chain terminators, while IFN alfa-2a inhibits translation of viral proteins. Combining agents that act at different sites of viral replication may improve HIV inhibition and produce more effective and sustained anti-HIV effects.

Detailed description: AZT and ddC inhibit HIV by acting as reverse transcriptase chain terminators, while IFN alfa-2a inhibits translation of viral proteins. Combining agents that act at different sites of viral replication may improve HIV inhibition and produce more effective and sustained anti-HIV effects.

Patients are randomly assigned to one of three treatment arms to receive AZT/ddC alone or combined with one of two doses of IFN alfa-2a. Treatment continues for up to 12 months after enrollment of the last patient. Patients are followed at 2, 4, and 8 weeks and every 8 weeks thereafter. Mean duration of follow-up is expected to be 13 months.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Isoniazid for \< grade 2 peripheral neuropathy (if patient is also taking 50 mg/day pyridoxine).
* Phenytoin for \< grade 2 peripheral neuropathy.
* A 21-day course of adjuvant systemic corticosteroid therapy for moderate to severe Pneumocystis carinii pneumonia (PCP).
* Chemoprophylaxis for PCP, candidiasis, herpes simplex infection (up to 1 g acyclovir daily), and Mycobacterium tuberculosis.

Patients must have:

* HIV infection.
* CD4 count \< 400 cells/mm3 within 30 days prior to study entry.

NOTE:

* Minimal Kaposi's sarcoma is allowed.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

* Active opportunistic infection requiring acute therapy.
* Need for maintenance therapy for cytomegalovirus infection, toxoplasmic encephalitis, or mycobacterial infection.
* Malignancy (other than minimal Kaposi's sarcoma) requiring therapy.
* Grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

* Other antiretroviral drugs, biologic response modifiers, cytotoxic chemotherapy, or investigational drugs (unless approved by the protocol chairs).
* Recombinant erythropoietin, G-CSF, or GM-CSF.
* Drugs that cause peripheral neuropathy, e.g., gold, hydralazine, nitrofurantoin, vincristine, cisplatin, disulfiram, and diethyldithiocarbamate (unless approved by the protocol chairs).

Concurrent Treatment:

Excluded:

* Radiation therapy (unless approved by the protocol chairs).

Patients with the following prior conditions are excluded:

* History of intolerance to AZT at 600 mg/day or less.
* Unexplained temperature of 38.5 degrees C persisting for 14 days or longer.
* Unexplained, chronic diarrhea defined as 3 or more stools per day persisting for 14 days or longer.

Prior Medication:

Excluded:

* Acute therapy for opportunistic infection within 14 days prior to study entry.
* Prior ddC, ddI, or IFN alfa-2a.

Active substance abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: La Jolla
country: United States
facility: Ucsd, Avrc Crs
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
Study officials:
name: Fischl MA
role: STUDY_CHAIR
name: Richman DD
role: STUDY_CHAIR
References:
citation: Fischl MA, Richman DD, Saag M, Meng TC, Squires KE, Holden-Wiltse J, Meehan PM. Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-alpha2a in patients with HIV. AIDS Clinical Trials Group Study 197. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Dec 1;16(4):247-53. doi: 10.1097/00042560-199712010-00005.