Clinical trial NCT00001062: A Study of Ganciclovir in the Treatment of Cytomegalovirus of the Eyes
Official title: A Phase I Study of a Fixed-Schedule Regimen of Alternating Oral and Intravenous Ganciclovir for Treatment of Cytomegalovirus Retinitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytomegalovirus Retinitis
HIV Infections
Keywords: Infusions, Intravenous
Ganciclovir
Administration, Oral
Acquired Immunodeficiency Syndrome
Antiviral Agents
Cytomegalovirus Retinitis
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 25
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine whether alternating oral ganciclovir with intravenous ( IV ) ganciclovir can prevent relapse of Cytomegalovirus ( CMV ) retinitis and improve quality of life in AIDS patients.

A systemic treatment strategy for CMV retinitis is needed that will be effective yet convenient to administer, without the need for a permanent indwelling IV catheter. Although oral ganciclovir has been used as maintenance following induction with IV ganciclovir, patients with reactivation of disease must be reinduced IV. A fixed-schedule regimen in which oral and IV ganciclovir are alternated may prevent reactivation and progression of disease, as opposed to the current therapeutic strategy in which changes in therapy are event-driven. Also, the duration of intermittent IV therapy required to control disease may be short enough to eliminate the need for an indwelling catheter.

Detailed description: A systemic treatment strategy for CMV retinitis is needed that will be effective yet convenient to administer, without the need for a permanent indwelling IV catheter. Although oral ganciclovir has been used as maintenance following induction with IV ganciclovir, patients with reactivation of disease must be reinduced IV. A fixed-schedule regimen in which oral and IV ganciclovir are alternated may prevent reactivation and progression of disease, as opposed to the current therapeutic strategy in which changes in therapy are event-driven. Also, the duration of intermittent IV therapy required to control disease may be short enough to eliminate the need for an indwelling catheter.

Patients receive IV induction with ganciclovir for 2 weeks followed by an alternating course of 3 weeks of oral ganciclovir and 1 week of IV drug for four cycles (16 weeks). If CMV retinitis fails to arrest after initial induction, IV ganciclovir is administered for an additional 2 weeks.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Erythropoietin, G-CSF, or GM-CSF.
* Antiretrovirals.

Patients must have:

* HIV infection.
* Evaluable CMV retinitis with photographable lesions.
* Life expectancy of at least 6 months.
* No active AIDS-defining opportunistic infections or malignancies that require nephrotoxic or myelosuppressive therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Evidence of retinal vascular or related infectious disease or other retinal lesions that would interfere with the ability to detect responses to therapy or progression.
* Corneal, lens, or vitreous opacification precluding funduscopic exam.
* Clinically significant pulmonary or neurologic impairment other than seizure disorder or CNS mass lesion.
* Inability to obtain temporary IV access.
* Requirement for permanent catheters for IV ganciclovir administration.
* Uncontrolled diarrhea or nausea preventing ingestion of medicine.
* Known hypersensitivity to IV or oral ganciclovir.

Concurrent Medication:

Excluded:

* Immunomodulators.
* Biologic response modifiers.
* Interferon.
* Related investigational agents.
* CMV prophylaxis.
* Systemic acyclovir.
* Any nephrotoxic agent.
* Any concomitant therapy that would prohibit use of ganciclovir.

Prior Medication:

Excluded:

* Prior treatment for CMV retinitis.
* More than 4 months of prior ganciclovir or foscarnet, or within 4 weeks prior to study entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: New York
country: United States
facility: Cornell University A2201
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Holland GN
role: STUDY_CHAIR
name: Hardy WD
role: STUDY_CHAIR
References:
citation: Danner SA, Matheron S. Cytomegalovirus retinitis in AIDS patients: a comparative study of intravenous and oral ganciclovir as maintenance therapy. AIDS. 1996 Dec;10 Suppl 4:S7-11.