# name
Clinical trials to assess adjuvant therapeutics for severe
                malaria.

# metadata.dc.description.abstract[].value
Despite potent anti-malarial treatment, mortality rates
                associated with severe falciparum malaria remain high. To
                attempt to improve outcome, several trials have assessed a
                variety of potential adjunctive therapeutics, however none to
                date has been shown to be beneficial. This may be due, at least
                partly, to the therapeutics chosen and clinical trial design
                used. Here, we highlight three themes that could facilitate the
                choice and evaluation of putative adjuvant interventions for
                severe malaria, paving the way for their assessment in
                randomized controlled trials. Most clinical trials of adjunctive
                therapeutics to date have been underpowered due to the large
                number of participants required to reach mortality endpoints,
                rendering these study designs challenging and expensive to
                conduct. These limitations may be mitigated by the use of
                risk-stratification of participants and application of surrogate
                endpoints. Appropriate surrogate endpoints include direct
                measures of pathways causally involved in the pathobiology of
                severe and fatal malaria, including markers of host immune and
                endothelial activation and microcirculatory dysfunction. We
                propose using circulating markers of these pathways to identify
                high-risk participants that would be most likely to benefit from
                adjunctive therapy, and further by adopting these biomarkers as
                surrogate endpoints; moreover, choosing interventions that
                target deleterious host immune responses that directly
                contribute to microcirculatory dysfunction, multi-organ
                dysfunction and death; and, finally, prioritizing where
                possible, drugs that act on these pathways that are already
                approved by the FDA, or other regulators, for other indications,
                and are known to be safe in target populations, including
                children. An emerging understanding of the critical role of the
                host response in severe malaria pathogenesis may facilitate both
                clinical trial design and the search of effective adjunctive
                therapeutics.

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Clinical trials to assess adjuvant therapeutics for severe
                malaria.