Clinical trial NCT00000776: Dexamethasone in Cryptococcal Meningitis
Official title: Dexamethasone in Cryptococcal Meningitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Meningitis, Cryptococcal
HIV Infections
Keywords: AIDS-Related Opportunistic Infections
Meningitis
Cryptococcosis
Dexamethasone
Drug Therapy, Combination
Fluconazole
Flucytosine
Acquired Immunodeficiency Syndrome
Amphotericin B
Brain Diseases
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 36
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of corticosteroids on reducing elevated intracranial pressure in cryptococcal meningitis. To evaluate the safety of corticosteroids in patients with cryptococcal meningitis and intracranial hypertension.

In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.

Detailed description: In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.

Patients are randomized to receive dexamethasone or placebo every 6 hours for 72 hours (days 1 through 3). Additionally, standard antifungal therapy with amphotericin B and flucytosine is given for 2 weeks, followed by fluconazole for 8 weeks. Lumbar punctures will be performed daily on days 1 through 3, on days 7 and 14, and at week 10.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Aerosolized pentamidine or systemic chemoprophylaxis for PCP.
* Preventive therapy for steroid-associated ulcers and any other therapies required to manage steroid toxicity (e.g., insulin).

Patients must have:

* Documented initial episode or relapse of acute cryptococcal meningitis. (NOTE: Patients must be untreated for this episode except for administration of a test dose of 1 g or less amphotericin B.)
* Acute cryptococcal meningitis with cerebrospinal fluid opening pressure \>= 250 mm H2O prior to receipt of antifungal therapy for this episode.
* Documented HIV infection OR a diagnosis of AIDS based on a documented AIDS-defining opportunistic infection.
* Ability to begin therapy within 8 hours after the pre-entry lumbar puncture.
* Consent of parent or guardian if less than 18 years of age.

NOTE:

* Comatose patients eligible provided informed consent can be provided by guardian or next of kin.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Concurrent CNS disease such as another infection or neoplasm that would interfere with assessment of response.
* Prison incarceration.

Concurrent Medication:

Excluded:

* Acetazolamide, mannitol, urea preparations, and other corticosteroids during the first 72 hours of the study.
* Treatment or prophylaxis with other systemic antifungal agents at any time.
* Antiretroviral therapy during the first 72 hours of the study.

Prior Medication:

Excluded within 7 days prior to study entry:

* Corticosteroids, mannitol, urea preparations, acetazolamide, or more than 24 hours of phenytoin.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Washington
country: United States
facility: Georgetown Univ Med Ctr
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Bronx
country: United States
facility: Jack Weiler Hosp / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Bronx Veterans Administration / Mount Sinai Hosp
state: New York
city: Brooklyn
country: United States
facility: SUNY / Health Sciences Ctr at Brooklyn
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
name: J Jacobson
role: STUDY_CHAIR
References: