Rosiglitazone to improve Outcome of Severe Infection
Study Acronym: ROSI
Principal investigators: Kevin Kain, Lena Serghides, Quique Bassat
This is a staggered phase I directly to phase IIb prospective, parallel arm, randomized, double-blind, placebo-controlled trial of adjunctive rosiglitazone 0.045mg/kg/dose twice daily for the duration of antimalarial treatment versus placebo in children with P. falciparum infection requiring hospitalization. The study is being conducted at CISM/Manhiça district hospital, located in the village of Manhiça in the northern part of Maputo province, in southern Mozambique.
Even with optimal antimalarial therapy and supportive care, severe and cerebral malaria are associated with a 10-30% mortality rate and neurocognitive deficits in up to 33% of survivors. Adjunctive therapies that modify host immune-pathological processes may further improve outcome over that possible with antimalarials alone. The investigators have generated extensive pre-clinical data demonstrating a protective role for PPARγ agonists in models of severe malaria.
The study commenced in 2016 aiming to translate these findings to informative patient populations by evaluating the utility of PPARγ agonists as adjunctive therapy for severe malaria. Numerous studies have reported long-term neurological sequelae and cognitive impairment in children surviving severe malaria, including memory, attention, speech, behaviour and language deficits. The study aimed to assess safety and clinical outcomes including neurocognitive impairment in survivors at a 6-month follow up.