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.
Author(s): 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(1), 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.
Affiliation(s): Author information:
(1)Oxford University Clinical Research Unit, Wellcome Trust Major Overseas
Programme Vietnam, Ho Chi Minh City, Vietnam. jbeardsley@oucru.org.
Publication date & source: 2014, Trials. , 15:441
BACKGROUND: Cryptococcal meningitis (CM) is a severe AIDS-defining illness with
90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It
is the leading cause of death in HIV patients in Asia and Africa.No major advance
has been made in the treatment of CM since the 1970s. The mainstays of induction
therapy are amphotericin B and flucytosine, but these are often poorly available
where the disease burden is highest. Adjunctive treatments, such as
dexamethasone, have had dramatic effects on mortality in other neurologic
infections, but are untested in CM. Given the high death rates in patients
receiving current optimal treatment, and the lack of new agents on the horizon,
adjuvant treatments, which offer the potential to reduce mortality in CM, should
be tested.The principal research question posed by this study is as follows: does
adding dexamethasone to standard antifungal therapy for CM reduce mortality?
Dexamethasone is a cheap, readily available, and practicable intervention.
METHOD: A double-blind placebo-controlled trial with parallel arms in which
patients are randomised to receive either dexamethasone or placebo, in addition
to local standard of care. The study recruits patients in both Asia and Africa to
ensure the relevance of its results to the populations in which the disease
burden is highest. The 10-week mortality risk in the control group is expected to
be between 30% and 50%, depending on location, and the target hazard ratio of 0.7
corresponds to absolute risk reductions in mortality from 30% to 22%, or from 50%
to 38%. Assuming an overall 10-week mortality of at least 30% in our study
population, recruitment of 824 patients will be sufficient to observe the
expected number of deaths. Allowing for some loss to follow-up, the total sample
size for this study is 880 patients. To generate robust evidence across both
continents, we aim to recruit roughly similar numbers of patients from each
continent. The primary end point is 10-week mortality. Ethical approval has been
obtained from Oxford University's Tropical Research Ethics Committee (OxTREC),
and as locally mandated at each site.
TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number:
ISRCTN59144167 26-July-2012.
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