Adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis

Conditions

Cryptococcus meningitis/HIV Infections and Infestations Cerebral cryptococcosis

Jonathan Kitonsa, Julius Kiwanuka, Zacchaeus Anywaine, Sheila Kansiime, Kenneth Katumba et al. (11 authors)

PLoS neglected tropical diseases2021-03-033 citations

10.1371/journal.pntd.0008983

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda

Jonathan Kitonsa, Rebecca N. Nsubuga, Yunia Mayanja, Julius Kiwanuka, Yofesi Nikweri et al. (11 authors)

PLoS neglected tropical diseases2020-11-3013 citations

10.1371/journal.pntd.0008823

Factors affecting mortality among HIV positive patients two years after completing recommended therapy for Cryptococcal meningitis in Uganda.

Kitonsa J, Mayanja Y, Aling E, Kiwanuka J, Namutundu J, Anywaine Z, Ggayi AB, Kibengo F, Kiwanuka N, Kaleebu P.

2019-01-3014 citations

10.1371/journal.pone.0210287

Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by <i>Talaromyces marneffei</i>.

Le T, Ly VT, Thu NTM, Nguyen A, Thanh NT, Chau NVV, Thwaites G, Perfect J, Kolamunnage-Dona R, Hope W.

2019-01-297 citations

10.1128/aac.01739-18

A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis

Thuy Le, Nguyễn Văn Kính, Ngo Thi Kim Cuc, Nguyen Le Nhu Tung, Nguyễn Thị Lâm et al. (24 authors)

New England Journal of Medicine2017-06-14181 citations

10.1056/nejmoa1613306

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis

Justin Beardsley, Marcel Wolbers, Freddie Kibengo, Abu-Baker Ggayi, Anatoli Kamali et al. (31 authors)

New England Journal of Medicine2016-02-11309 citations

10.1056/nejmoa1509024

CryptoDex: a randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial.

Day J, Imran D, Ganiem AR, Tjahjani N, Wahyuningsih R, Adawiyah R, Dance D, Mayxay M, Newton P, Phetsouvanh R, Rattanavong S, Chan AK, Heyderman R, van Oosterhout JJ, Chierakul W, Day N, Kamali A, Kibengo F, Ruzagira E, Gray A, Lalloo DG, Beardsley J, Binh TQ, Chau TT, Chau NV, Cuc NT, Farrar J, Hien TT, Van Kinh N, Merson L, Phuong L, Tho LT, Thuy PT, Thwaites G, Wertheim H, Wolbers M.

2014-11-1222 citations

10.1186/1745-6215-15-441

Interventions

Eligible participants will randomly be allocated to either dexamethasone or placebo group. Dexamethasone will be given in a reducing dose according to body weight. This dose is identical to the dos

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Age >18 years 2. HIV antibody positive 3. Cryptococcal meningitis defined as a syndrome consistent with CM and one or more of: 3.1. Positive CSF India ink (budding encapsulated yeasts) 3.2. C. neoformans cultured from CSF or blood 3.3. Positive cryptococcal antigen Lateral Flow Antigen Test (LFA) in CSF 4. Informed consent to participate given by patient or acceptable representative

Exclusion criteria

Exclusion criteria: Current exclusion criteria as of 23/09/2014: 1. Pregnancy 2. Active gastrointestinal bleeding (defined as vomiting blood or malaena stool in the previous week) 3. Currently receiving treatment for cryptococcal meningitis and having received > 1 week of anti-cryptococcal meningitis therapy 4. Known allergy to dexamethasone 5. Current steroid use defined as: 5.1. Currently receiving the equivalent of prednisolone 40 mg/day or more 5.2. Currently receiving steroid therapy (any dose) for more than 3 weeks (except topical steroids which are permitted) 6. Concurrent condition for which corticosteroids are indicated because of proven benefit (such as severe Pneumocystis pneumonia [pO23*ULN, despite adequate hydration) Previous exclusion criteria: 1. Pregnancy 2. Active gastrointestinal bleeding (defined as vomiting blood or malaena stool in the previous week) 3. Currently receiving treatment for cryptococcal meningitis and having received > 1 week of anti-cryptococcal meningitis therapy 4. Known allergy to dexamethasone 5. Current steroid use defined as: 5.1. Currently receiving the equivalent of prednisolone 40 mg/day or more 5.2. Currently receiving steroid therapy (any dose) for more than 3 weeks (except topical steroids which are permitted) 6. Renal failure (defined as creatinine >3*ULN, despite adequate hydration)

Design outcomes

Primary

Measure	Time frame
Overall survival until 10 weeks after randomisation	—

Secondary

Measure	Time frame
1. Survival until 6 months after randomization 2. Disability at 10 weeks and 6 months 3. Rate of CSF sterilisation during the first 2 weeks 4. Adverse events 5. Rate of IRIS until 10 weeks 6. Time to new AIDS-defining illnesses or death until 10 weeks 7. Visual deficit at 10 weeks 8. Time to new neurological event or death until 10 weeks 9. Longitudinal measurements of intracranial pressure during the first 2 weeks 10. Antifungal treatment intensification or re-treatment for cryptococcal meningitis in the 6 months post randomisation	—

Measure

Time frame

1. Survival until 6 months after randomization 2. Disability at 10 weeks and 6 months 3. Rate of CSF sterilisation during the first 2 weeks 4. Adverse events 5. Rate of IRIS until 10 weeks 6. Time to new AIDS-defining illnesses or death until 10 weeks 7. Visual deficit at 10 weeks 8. Time to new neurological event or death until 10 weeks 9. Longitudinal measurements of intracranial pressure during the first 2 weeks 10. Antifungal treatment intensification or re-treatment for cryptococcal meningitis in the 6 months post randomisation

—

Countries

Indonesia, Laos, Malawi, Thailand, Uganda, Viet Nam

Outcome results

None listed