Clinical trial NCT00000953: Comparison of Brovavir Versus Acyclovir in the Treatment of Herpes in HIV-Infected Patients
Official title: Evaluation of Brovavir ( BV-ara-U; SQ 32,756 ) Versus Acyclovir in the Treatment of Localized Herpes Zoster in HIV-Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Chickenpox
Keywords: Herpes Zoster
Acyclovir
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
sorivudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Bristol-Myers Squibb
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To compare the efficacy of oral sorivudine (brovavir) and oral acyclovir for the treatment of localized herpes zoster in HIV-infected patients.

HIV-infected patients are at high risk for herpesvirus infections, including varicella-zoster virus ( VZV ) infections, also called shingles. Acyclovir, an approved drug, is widely used to treat VZV infections in the HIV population. Since no data from controlled studies are available to define the role of antiviral therapy for VZV infections in HIV-infected patients, a study is needed to test the relative efficacy of brovavir, an experimental antiviral drug, versus that of acyclovir.

Detailed description: HIV-infected patients are at high risk for herpesvirus infections, including varicella-zoster virus ( VZV ) infections, also called shingles. Acyclovir, an approved drug, is widely used to treat VZV infections in the HIV population. Since no data from controlled studies are available to define the role of antiviral therapy for VZV infections in HIV-infected patients, a study is needed to test the relative efficacy of brovavir, an experimental antiviral drug, versus that of acyclovir.

One hundred-eighty patients are randomized to receive either brovavir or acyclovir as follows: brovavir or its matching placebo once daily and acyclovir or its matching placebo five times daily. Treatment continues for 10 days. Entry into the study must occur within 72 hours of lesion development. Patients are followed in person daily or at regular intervals during study drug administration and on days 14, 21, and 28, and then monthly by telephone for 11 months thereafter.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Medication for concurrent conditions (e.g., insulin, antihypertensives, bronchodilators, digoxin) or antibacterials or antifungals to treat concurrent infections at other sites or superinfection of the zoster lesion.
* Anti-inflammatory, analgesic (including narcotic analgesic), or antipyretic agents.
* Antidepressants and antipsychotics such as amitriptyline and/or fluphenazine.
* Nerve blocks.
* AZT, ddI, ddC, and amantadine.
* Low-dose corticosteroids for treatment of an underlying (not zoster-related) disease.
* Immune modulators without varicella-zoster virus activity (e.g., GM-CSF, gp160 vaccine).

Patients must have:

* HIV infection.
* Localized, cutaneous herpes zoster (shingles).
* Zoster-associated rash present for 3 or fewer days prior to entry.

Prior Medication:

Allowed:

* Zidovudine.
* ddI.
* ddC.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions and symptoms are excluded:

* Chickenpox.
* Evidence of visceral dissemination (organ involvement, i.e., brain, liver, or lung) and/or cutaneous dissemination (more than 20 vesicles in dermatomes beyond contiguous dermatomes) of zoster.
* Zoster-like lesion caused by organism other than VZV (e.g., HSV, enterovirus, or Mycoplasma).
* Bacterial superinfection of zoster lesion.
* Zosteriform lesion previously treated with topical antiviral agents.
* Acute, life-threatening opportunistic infection requiring treatment (ongoing suppressive or prophylactic maintenance therapy other than ganciclovir or foscarnet is permitted).
* Concurrent severe disease that may either impair ability to take oral medication in capsule or tablet form or limit survival during the 10-day treatment period or during acute phase follow-up (28 days).
* Suspected acute deterioration of renal or hepatic function.
* Mental impairment that precludes ability to comply with protocol.
* Any condition that would render the patient unsuitable for treatment.

Concurrent Medication:

Excluded during acute phase of study:

* Antiviral medications other than AZT, ddI, ddC, or anti-Parkinson's drugs (i.e., amantadine).
* Interferon.
* Isoprinosine.
* Levamisole.
* Transfer factor.
* Topical virucidal agents, oxidizing agents, DMSO, cell division-stimulating/healing agents, or astringents.
* Topical anesthetics (such as capsaicin or xylocaine).
* Topical creams or ointments that may interfere with evaluation of zoster lesions.
* Cimetidine.
* Fluorouracil or its derivatives, flucytosine, or cyclophosphamide (during drug administration and for 2 weeks thereafter).
* High-dose corticosteroids.
* Anticoagulant therapy (heparin locks and low-dose warfarin sodium permitted).
* Probenecid or derivatives.
* Treatment for any acute, life-threatening opportunistic infection (suppressive or prophylactic maintenance therapy other than ganciclovir or foscarnet is permitted).

Use of the following drugs is discouraged during the long-term phase of the study:

* Antiviral agents with VZV activity.
* Immunomodulators with presumed VZV activity.
* VZV immune globulin.
* Capsaicin.
* Cimetidine.

Patients with the following prior conditions are excluded:

* History of immediate hypersensitivity or serum sickness reaction or idiosyncratic reaction (such as hepatic necrosis or Stevens-Johnson syndrome) to any nucleoside analog antiviral agent or to any anticancer therapy with cytolytic agents.

Prior Medication:

Excluded within 1 month prior to entry:

* Any investigational drugs or treatments not licensed for any indication (other than ddI or ddC).

Excluded within 2 weeks prior to entry:

* Any systemic antiviral therapy, including ganciclovir, foscarnet, vidarabine, acyclovir, or ribavirin.
* Any antiretroviral drug other than zidovudine, ddI, and ddC.
* Immune globulin (e.g., IgG, VZIG).

Excluded within 72 hours prior to entry:

* Cyclophosphamide.
* Flucytosine.
* Fluorouracil or its derivatives.

Alcohol or drug abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA Med Ctr
state: California
city: Martinez
country: United States
facility: Veterans Administration Med Ctr
state: California
city: Oakland
country: United States
facility: Infectious Disease Med Group
state: California
city: San Diego
country: United States
facility: San Diego Naval Hosp
state: California
city: San Francisco
country: United States
facility: Mount Zion Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Washington
country: United States
facility: George Washington Univ Med Ctr
state: District of Columbia
city: Washington
country: United States
facility: Veterans Administration Med Ctr / Community AIDS Program
state: District of Columbia
city: Augusta
country: United States
facility: Med College of Georgia
state: Georgia
city: Honolulu
country: United States
facility: Univ of Hawaii / Leahi Hosp
state: Hawaii
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: Bethesda
country: United States
facility: Natl Institutes of Health / NIAID
state: Maryland
city: Boston
country: United States
facility: Massachusetts Gen Hosp / Harvard Med School
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Hosp
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp
state: Massachusetts
city: Boston
country: United States
facility: New England Deaconess Hosp
state: Massachusetts
city: St Louis
country: United States
facility: Washington Univ
state: Missouri
city: Albuquerque
country: United States
facility: Univ of New Mexico
state: New Mexico
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Mem Sloan - Kettering Cancer Ctr
state: New York
city: New York
country: United States
facility: Saint Luke's - Roosevelt Hosp Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Stony Brook
country: United States
facility: SUNY / Health Sciences Ctr at Stony Brook
state: New York
city: Syracuse
country: United States
facility: SUNY / Health Sciences Ctr at Syracuse
state: New York
city: Charlotte
country: United States
facility: Carolinas Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ Dermatology Associates
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ / ACTU-Univ Clinic
state: Ohio
city: Dayton
country: United States
facility: Dayton Veterans Administration Med Ctr
state: Ohio
city: Toledo
country: United States
facility: Med College of Ohio
state: Ohio
city: Portland
country: United States
facility: Portland Veterans Adm Med Ctr / Rsch & Education Grp
state: Oregon
city: Dallas
country: United States
facility: Dallas Veterans Administration Med Ctr
state: Texas
city: Dallas
country: United States
facility: Univ of Texas, Southwestern Med Ctr of Dallas
state: Texas
city: Galveston
country: United States
facility: Univ TX Galveston Med Branch
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Univ TX San Antonio Health Science Ctr
state: Texas
city: Temple
country: United States
facility: Scott and White Hosp
state: Texas
city: Charlottesville
country: United States
facility: Univ of Virginia Health Sciences Ctr
state: Virginia
city: Norfolk
country: United States
facility: Virginia Clinical Research Inc
state: Virginia
city: Salem
country: United States
facility: Salem Veterans Administration Med Ctr
state: Virginia
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: Wauwatosa
country: United States
facility: Great Lakes Hemophilia Foundation
state: Wisconsin
Study officials:
name: Crumpacker C
role: STUDY_CHAIR
References:
citation: Gnann J, et al. Sorivudine (BV-araU) versus acyclovir for Herpes zoster in HIV-infected patients. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:55