Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis

This study has been completed.
Sponsor:
Collaborators:
Doris Duke Charitable Foundation
University of Pennsylvania
Information provided by (Responsible Party):
Gregory Bisson, Botswana-UPenn Partnership
ClinicalTrials.gov Identifier:
NCT00976040
First received: September 11, 2009
Last updated: February 3, 2012
Last verified: February 2012

September 11, 2009
February 3, 2012
September 2009
November 2011   (final data collection date for primary outcome measure)
Change in the CSF CFUs between the immediate and standard ART initiation groups [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00976040 on ClinicalTrials.gov Archive Site
  • Grade 3 or 4 adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    each participant is followed up for 6 months after the initiation of HAART
  • Clearance of C. neoformans antigen from CSF and blood. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in the number of peripheral blood mononuclear cells responding to C. neoformans [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Grade 3 or 4 adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Clearance of C. neoformans antigen from CSF and blood. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in the number of peripheral blood mononuclear cells responding to C. neoformans [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis
A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis

The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis.

The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment.

Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cryptococcal Meningitis
  • HIV Infections
Other: Early antiretroviral therapy

The intervention is early initiation of antiretroviral therapy after diagnosis of Cryptococcal meningitis.

In the intervention/experimental arm, triple-drug highly active antiretroviral therapy regimens will be initiated within 7 days of diagnosis of Cryptococcal meningitis.

  • Experimental: Early antiretroviral therapy
    Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment.
    Intervention: Other: Early antiretroviral therapy
  • No Intervention: Standard antiretroviral therapy
    Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment.
Bisson GP, Molefi M, Bellamy S, Thakur R, Steenhoff A, Tamuhla N, Rantleru T, Tsimako I, Gluckman S, Ravimohan S, Weissman D, Tebas P. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis. 2013 Apr;56(8):1165-73. doi: 10.1093/cid/cit019. Epub 2013 Jan 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
December 2011
November 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load.
  • Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen
  • ART naive at the time of enrollment
  • 21 years old and above
  • Ability and willingness to give written informed consent to participate in the study
  • Able (as assessed by the patient's medical team)to initiate amphotericin B for cryptococcal meningitis
  • Initiated amphotericin B 72 hours or less prior to assessment for enrollment or not on amphotericin B at the time of assessment for enrollment
  • Agrees to obtain outpatient care after discharge within 50 kilometers from Princess Marina Hospital,Scottish Livingstone Hospital and Bamalete Lutheran Hospital

Exclusion Criteria:

  • Recent (within the past 4 weeks) antifungal use
  • Pregnant or breastfeeding
  • Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment.
  • Bacterial meningitis at the time of assessment for enrollment.
  • Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators.
  • Judged by study coordinator to be likely to initiate chemotherapy or any other immunomodulatory therapy prior to the 4 week LP.
  • Imprisoned.
Both
21 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Botswana
 
NCT00976040
THE BOTSHELO STUDY
Yes
Gregory Bisson, Botswana-UPenn Partnership
Botswana-UPenn Partnership
  • Doris Duke Charitable Foundation
  • University of Pennsylvania
Principal Investigator: Gregory P Bisson, MD,MSCE Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Principal Investigator: Pablo Tebas, MD Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Botswana-UPenn Partnership
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP