A Study of Cidofovir in HIV-Infected Children With Cytomegalovirus (CMV) Disease

NCT00000881 | Withdrawn Phase 1

• 2 other identifiers: ACTG 35211321
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Part A: To determine the safety and pharmacokinetics of sequential single doses of cidofovir in HIV-infected children with end-organ cytomegalovirus (CMV) disease. Part B: To determine the safety (including time to progression of CMV retinitis by retinal exam), pharmacokinetics, and long-term (6 months) tolerance of multiple-dose cidofovir in HIV-infected children with CMV retinitis. Part B: To determine the effect of multiple-dose cidofovir on the virologic parameters of CMV retinitis (viral load, shedding, and resistance to antiviral agents). \[AS PER AMENDMENT 1/7/98: To determine the safety, tolerance and pharmacokinetics of sequential single doses of cidofovir in HIV-infected children with CMV retinitis. To determine the safety (including time to progression of CMV retinitis by retinal exam), pharmacokinetics, and long-term (6-month) tolerance of multiple doses of cidofovir in HIV-infected children with CMV retinitis.\] While the intravenous formulation of cidofovir has been approved for the treatment of CMV retinitis in HIV-infected individuals, information is limited regarding its safety and tolerance in HIV-infected children. Intravenous cidofovir requires less frequent administration for both induction and maintenance therapy of CMV retinitis than other currently available therapies. If found to be safe and well tolerated in HIV-infected children with CMV retinitis, intravenous cidofovir would add significantly to agents available to treat this debilitating opportunistic infection.

Conditions

Cytomegalovirus Infections; Cytomegalovirus Retinitis; HIV Infections

Keywords

AIDS-Related Opportunistic Infections; Cytomegalovirus Infections; Antiviral Agents; cidofovir

Interventions

Cidofovir DRUG

Probenecid DRUG

Eligibility Criteria

• Age: 3 Months - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Ganciclovir therapy (for patients on Part A).\[AS PER AMENDMENT 1/7/98:
• Ganciclovir required during sequential single-dose phase.\]
• Antiretroviral medications, including protease inhibitors.
• Antibacterials except for aminoglycosides.
• IVIG.
• Antihistamines, antiemetics, and acetaminophen.
• Patients must have:
• Documented laboratory evidence of HIV-1 infection as demonstrated by:
• \< 18 months of age:
• a positive viral culture and a second confirmatory test (from a later date) of either a positive viral culture, p24 antigen, or PCR. Confirmatory tests must be completed at an ACTG certified laboratory.
• \>= 18 months of age:
• criteria as stated for \< 18 months or 2 positive tests for HIV antibody obtained after 18 months of age (drawn from two different dates). HIV antibody tests must be determined by a federally licensed ELISA. One of the two positive HIV antibody tests must be confirmed by any of the confirmatory tests (Western blot or IFA).
• Part A:

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions are excluded:
• Acute infections requiring treatment during the study period.
• Concurrent Medication:
• Excluded:
• Cancer chemotherapeutic agents. \[AS PER AMENDMENT 1/7/98:Anti-cancer therapy prohibited during multi-dosing phase.\]
• Excluded within 7 days prior to enrollment:
• Foscarnet therapy.
• Drugs known to cause nephrotoxicity such as amphotericin B, aminoglycosides, vancomycin, or IV pentamidine.
• Other local or systemic anti-CMV medications (except concomitant ganciclovir for patients treated on Part A).
• Patients with the following prior conditions are excluded:
• Previous hypersensitivity reaction to probenecid and/or serious allergic reaction (e.g., anaphylactic reaction, hypotension, laryngospasm, exfoliative dermatitis) to sulfa-containing medications.
• \[AS PER AMENDMENT 1/7/98:
• Pre-existing uveitis/iritis as determined by slit-lamp exam.
• Intraocular pressure \< 4 mm Hg prior to enrollment.\]

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

MeSH Terms

Conditions

Cytomegalovirus Infections; Cytomegalovirus Retinitis; HIV Infections; AIDS-Related Opportunistic Infections

Interventions

Cidofovir; Probenecid

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Eye Infections, Viral; Eye Infections; Eye Diseases; Retinitis; Retinal Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Opportunistic Infections

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Sulfones; Sulfur Compounds

Study Officials

• Dankner W

  STUDY CHAIR

• Spector S

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Last Updated: October 29, 2021

Record last verified: 2021-10