A Randomized Multicenter Phase II Trial of Recombinant Tumor Necrosis Factor and Recombinant Human Interferon-gamma in Patients With AIDS Related Complex


Phase 2
18 Years
70 Years
Not Enrolling
Both
HIV Infections

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Trial Information

A Randomized Multicenter Phase II Trial of Recombinant Tumor Necrosis Factor and Recombinant Human Interferon-gamma in Patients With AIDS Related Complex


Recombinant TNF and recombinant IFN-G have been shown to be effective against the virus
which causes AIDS and ARC in some laboratory studies, but may increase virus replication in
other laboratory studies. Previous studies in humans showed no increase in virus cultures
and some decrease in measurements of virus. Extensive preclinical data show that TNF and
IFN-G are more effective together than separately in laboratory and animal studies. As
single agents, both TNF and IFN-G have modest effect against HIV. Studies have demonstrated
that TNF and IFN-G, in combination, can not only inhibit HIV infection of previously
uninfected cells, but also can selectively induce the destruction of acutely infected target
cells.

Patients with ARC who are positive for HIV antibody are randomized to receive one of three
treatment arms: (1) TNF alone by intramuscular injection (IM); (2) IFN-G alone by IM; (3)
TNF plus IFN-G. Patients receive IM injections 3 times weekly for 4 months (16 weeks).
Repeated physical examinations and laboratory tests are used to monitor patients' safety.
Serial HIV cultures and core antigen assays are employed to obtain evidence of antiviral
activity and serial T cell and skin tests are used to measure immunologic effect.

Inclusion Criteria


Inclusion Criteria

Patients who have a primary diagnosis of AIDS related complex (ARC) including
lymphadenopathy syndrome (LAS), who are positive for HIV antibody, have a minimum life
expectancy of 3 months, and have one or more of the following symptoms for = or > 30 days:

- Fever.

- Night sweats.

- Fatigue.

- Oral thrush.

- Hairy leukoplakia.

- Diarrhea.

- Weight loss < 10 percent.

- Patients must be able to sign a written informed consent form, which must be obtained
prior to treatment.

Concurrent Medication:

Allowed:

- Acetaminophen for temperature rise of > 38.5 degrees C - 650 mg by mouth every 4
hours on an as needed basis.

Severe rigors may be treated (or prevented) with meperidine 50 mg IV on an as needed basis
in the absence of systolic hypotension < 80 mm Hg.

-

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

- Clinically significant cardiac disease - New York Heart Association Class II, III, or
IV.

- Hemorrhagic diathesis (including hemophilia) or active bleeding disorder (e.g.,
genitourinary, gastrointestinal).

- Clinically apparent vascular disease (including a prior history of pulmonary embolus,
deep venous thrombosis, or peripheral arterial occlusive disease).

Concurrent Medication:

Excluded:

- Medications required for the treatment of active cardiac disease including cardiac
glycosides, antiarrhythmics and antianginal agents.

- Anticoagulants.

- Thrombolytic agents.

- Nonsteroidal anti-inflammatory drugs.

- Ongoing therapy with vasodilators.

- Aspirin.

- Corticosteroids.

- Antihistamines.

- Barbiturates.

- Excluded within 4 weeks of study entry:

- Antiviral chemotherapy.

- Immunotherapy.

- Excluded within 12 weeks of study entry:

- Suramin.

Patients with the following are excluded:

- AIDS-associated opportunistic infection.

- Lipoprotein disorders.

- Hemophilia.

Prior Medication:

Excluded:

- Interferon gamma.

- Tumor necrosis factor.

Type of Study:

Interventional

Study Design:

Masking: Double-Blind, Primary Purpose: Treatment

Principal Investigator

Kaplan L

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 025

NCT ID:

NCT00001004

Start Date:

Completion Date:

February 1990

Related Keywords:

  • HIV Infections
  • Tumor Necrosis Factor
  • Interferon-gamma, Recombinant
  • HIV Antigens
  • Immunologic Surveillance
  • Drug Therapy, Combination
  • Acquired Immunodeficiency Syndrome
  • AIDS-Related Complex
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • AIDS-Related Complex
  • Necrosis

Name

Location
Univ of Washington Seattle, Washington  98105