Early Versus Delayed Antiretroviral Therapy (ART) in the Treatment of Cryptococcal Meningitis in Africa

NCT00830856 | Completed DMC

• 1 other identifier: ZimCrypto03
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Cryptococcal Meningitis continues to be one of the most devastating AIDS defining illness in sub-Saharan Africa. Despite the availability of azoles such as fluconazole for treatment, mortality remains high with some studies showing 100% mortality. The investigators designed a study to determine if timing of the initiation of antiretroviral therapy (ART) in patients with cryptococcal meningitis and HIV would improve survival. The investigators hypothesis was that early initiation of ART result in improved mortality for patients with HIV and cryptococcal meningitis.

Conditions

Cryptococcal Meningitis; HIV Infections

Keywords

Cryptococcal Meningitis; HIV; Fluconazole; Antiretroviral therapy; Africa; treatment naive

Outcome Measures

Primary Outcomes (1)

• Mortality

  2 years

Study Arms (2)

1

EXPERIMENTAL

Early initiation of antiretroviral therapy. Patients in this treatment group were started on Fluconazole 800mg by mouth every day for Cryptococcal Meningitis, and within 72hrs of diagnosis were started on First line antiretroviral therapy per Zimbabwe treatment guidelines which is Stavudine, Lamivudine and Nevirapine.

Drug: Fluconazole; Drug: Fixed dose - Stavudine, lamivudine and Nevirapine

2

EXPERIMENTAL

Delayed initiation of antiretroviral therapy. Patients in this treatment group were started on Fluconazole 800mg by mouth every day for Cryptococcal Meningitis, and after completion of high dose fluconazole for 10 weeks, the patients in this group were started on First line antiretroviral therapy per Zimbabwe treatment guidelines which is Stavudine, Lamivudine and Nevirapine.

Drug: Fluconazole; Drug: Fixed dose - Stavudine, Lamivudine, Nevirapine

Interventions

Fluconazole DRUG

Fluconazole 800mg po qday

1; 2

Fixed dose - Stavudine, lamivudine and Nevirapine DRUG

Initiation within 72 hours of diagnosis of Cryptococcal meningitis.

1

Fixed dose - Stavudine, Lamivudine, Nevirapine DRUG

Delayed initiation of ART defined as 10 weeks after initiation of high dose fluconazole therapy.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infection documented by a positive HIV antibody test at enrollment;
• Adult men and women (age\>18);
• Cryptococcal meningitis infection documented by a positive CSF CRAG or CSF identification of C. neoformans.
• Place of residence is located within a 50km radius of Harare.

You may not qualify if:

• Previous diagnosis (\>1 week) of and treatment for cryptococcal meningitis
• Currently on ARVs, or have been intermittently on and off ART in the past.
• Concurrent use of medications that affect the metabolism of fluconazole e.g., antiseizure medications, oral hypoglycaemic agents.
• History of cardiac failure and or predisposition to arrhythmias will be excluded.
• They are pregnant or active lactation women
• History of active hepatitis or hepatic or renal dysfunction will be excluded.

Sponsors & Collaborators

• University of Zimbabwe: lead
• AIDS Care Research in Africa: collaborator

Study Sites (1)

University of Zimbabwe, College of Health Sciences

Harare, Harare, Zimbabwe

Location

Related Publications (1)

• Makadzange AT, Ndhlovu CE, Takarinda K, Reid M, Kurangwa M, Gona P, Hakim JG. Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa. Clin Infect Dis. 2010 Jun 1;50(11):1532-8. doi: 10.1086/652652.

  PMID: 20415574 DERIVED

MeSH Terms

Conditions

Meningitis, Cryptococcal; HIV Infections

Interventions

Fluconazole; Stavudine; Lamivudine; Nevirapine

Condition Hierarchy (Ancestors)

Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Cryptococcosis; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Pyridines

Study Officials

• Chiratidzo E Ndhlovu, MBChB, FRCP

  University of Zimbabwe, Department of Medicine

  PRINCIPAL INVESTIGATOR

• Azure T Makadzange, MD, DPhil

  University of Zimbabwe, Department of Immunology

  PRINCIPAL INVESTIGATOR

• James Hakim, MBChB, FRCP

  University of Zimbabwe, Department of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 28, 2009
• Study Start: October 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2009
• Last Updated: July 18, 2016

Record last verified: 2016-07

Locations

ZI (1)