FUNDING ORGANIZATION	RESEARCH ORGANIZATION	PROGRAM	DIRECTOR	CITY	COUNTRY	ABSTRACT
	MRC	MAKERERE UNIVERSITY	A RANDOMISED TRIAL OF MONITORING PRACTICE AND PULSE ANTIRETROVIRAL THERAPY IN AFRICAN CHILDREN WITH HIV INFECTION (ARROW TRIAL)	MUSOKE, P	KAMPALA	UGANDA	View
Junior DART is a randomised open-label trial enrolling 1200 African HIV-infected children, aged 6 months to 18 years, with an adult carer in the DART (Development of AntiRetroviral Therapy) trial which has enrolled 2000 of 3000 adults in Uganda (2 sites) and Zimbabwe (1 site). Junior DART will take place in the same sites and the 2 trial teams will work closely together. Junior DART will have two major randomisations: to clinical monitoring only (CMO) versus laboratory and clinical monitoring (LCM); and to intermittent (planned treatment interruptions, PTI) versus continuous ART. In a further randomised substudy, 3 regimen strategies for initiating ART will be compared in terms of HIV RNA viral load response. Eligible children should have paediatric WHO Stage 2 or 3 disease, and CD4 percent 20% for children 2 years, 15% for children 2-11 years, or CD4 count 200 cells/mm3 for those aged 12-18 years. It is expected that at least 750 children randomised to CMO versus LCM will be 2 years and have achieved a sufficient increase in CD4 (CD4 ?20% for 2-11 years and CD4 250 cells/mm3 for 12-18 years) by 48 or 72 weeks to be eligible for the second randomisation to PTI versus continuous ART. This will only open after a non-randomised pilot study of PTIs in 100 children satisfying these threshold criteria has been completed (with all children having monthly CD4 measurements) and the DSMC and Trial Steering Committee have assessed the safety of the proposed PTI strategy. Recruitment into the trial will take place over one year with minimum follow-up of 4 years. First and second-line ART will be available for all children (for up to five years). The decision to change to second-line ART will be based on clinical criteria alone for the CMO arm and on clinical plus laboratory criteria for the LCM arm. Issues of after-trial ART are being negotiated with governments in the same way as for adult DART. The primary efficacy endpoint will be progression to a new paediatric WHO stage 3 (AIDS) event or death in children under 13 years, or adult WHO stage 4 disease for those 13 years and older. The primary outcome for the randomised substudy will be change in HIV RNA from baseline to 48 weeks, performed retrospectively on stored plasma samples.
	MRC	MAKERERE UNIVERSITY	RANDOMISED TRIAL OF FLUID RESUSCITATION STRATEGIES IN AFRICAN CHILDREN WITH SEVERE FEBRILE ILLNESS & IMPAIRED PERFUSION	KIGULI, S	KAMPALA	UGANDA	View
In hospitals throughout sub-Saharan Africa (SSA) case fatality rates for severe infections in childhood remains at 15-30%. Curently, antimalarial and antimicrobial drugs are the mainstay of treatment, however most deaths occur early, due to the complications of severe illness, and before definitive treatments have time to act. In this situation doctors have to rely upon supportive therapies to treat complications and try to improve outcome. Defining which are the best life saving treatments has been frustrated by the lack of clinical trials addressing this issue. Correction of fluid deficits by rapid infusion (volume expansion) is practised routinely for sick children presenting for emergency care and would be a logical supportive treatment for children with severe illness with signs of impaired perfusion. Opinion of this perspective remains divided. Reticence to adopt this approach remains and thus in African hospitals children are managed with little fluid or no additional fluid or with blood transfusion despite the concerns over cost and long-term risk of infection. The FEAST trial is a large pragmatic randomised controlled trial in African children at 6 hospitals in SAA. It aims to address the question of whether the addition of fluid resuscitation to the standard case management to rapidly restore intravascular volume depletion of African children with severe febrile illness and clinical evidence of impaired perfusion is safe and results in improved survival compared to standard management alone. More specifically, the trial has been designed with the aim of resolving whether rapid correction of intravascular volume, using colloidal (albumin) or electrolyte solutions (saline), is safe and improves both survival and neurological outcome in children with severe falciparum malaria rather than the slow restoration of total body water deficits suggested by other clinical researchers and currently recommended in international guidelines. Most interventions will be given in the first two hours after admission. Children will be monitored for 48 hours. The primary endpoint is in-hospital mortality at 48 hours post randomisation. If benefit were shown it could potentially save thousands of lives of young children annually. An initial estimate of cost-effectiveness suggests that albumin would be cost-effective compared to no treatment for a decision maker willingness to pay $35 or $5.33 per life year gained. If albumin were superior to saline or standard of care then investment in translating the newer technologies to large regional blood transfusion services to produce a cheap, regional source of albumin would be necessary.