EDCTP portfolio: Neglected infectious diseases

The PediCAP study aims to identify the optimal treatment for children hospitalised with severe pneumonia.

Optimising treatment of childhood pneumonia

Pneumonia is the leading cause of death of children under five years of age. Globally, it kills an estimated 1.4 million children every year, and accounts for 18% of deaths of young children. An estimated 500,000–750,000 of these deaths occur in sub-Saharan Africa.

WHO recommends that hospitalised children with severe or very severe pneumonia should be given injectable antibiotics for at least five days. However, this leads to long hospital stays, high costs and an increased risk of hospital-acquired infection.

The challenge

The PediCAP study is investigating less intensive treatment strategies based on a switch from injected to oral antibiotics, for which little evidence currently exists. Treatment could be switched to amoxicillin, or to a co-amoxiclav, a combination of amoxicillin and a second type of antibiotic; the latter would protect against a wider range of bacteria but could have more side effects and might select for antibiotic resistance. It is also unclear how long oral antibiotics should be given for – courses should be long enough to kill pathogens but not so long that they promote the development of resistance.

The PediCAP team will use an innovative trial design to compare the switch from injected antibiotics to either amoxicillin or to co-amoxiclav, and to assess different durations of treatment. As well as recovery rates, the trial will monitor side effects and the development of resistance. It will also examine whether optimal duration of treatment depends on factors such as age or severity of disease, which could allow treatment regimes to be tailored to particular subsets of patients.

The project

The PediCAP study will fill a large gap in the evidence base for treatment of pneumonia in children. As increasing numbers of children are being treated for pneumonia in hospital, optimised treatments that achieve high cures rates while minimising lengths of hospital stay, side effects and resistance could have a major impact.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Pneumonia is the leading cause of death of children under five years of age. Globally, it kills an estimated 1.4 million children every year, and accounts for 18% of deaths of young children. An estimated 500,000–750,000 of these deaths occur in sub-Saharan Africa.

WHO recommends that hospitalised children with severe or very severe pneumonia should be given injectable antibiotics for at least five days. However, this leads to long hospital stays, high costs and an increased risk of hospital-acquired infection.

The PediCAP study is investigating less intensive treatment strategies based on a switch from injected to oral antibiotics, for which little evidence currently exists. Treatment could be switched to amoxicillin, or to a co-amoxiclav, a combination of amoxicillin and a second type of antibiotic; the latter would protect against a wider range of bacteria but could have more side effects and might select for antibiotic resistance. It is also unclear how long oral antibiotics should be given for – courses should be long enough to kill pathogens but not so long that they promote the development of resistance.

The PediCAP team will use an innovative trial design to compare the switch from injected antibiotics to either amoxicillin or to co-amoxiclav, and to assess different durations of treatment. As well as recovery rates, the trial will monitor side effects and the development of resistance. It will also examine whether optimal duration of treatment depends on factors such as age or severity of disease, which could allow treatment regimes to be tailored to particular subsets of patients.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The PediCAP study will fill a large gap in the evidence base for treatment of pneumonia in children. As increasing numbers of children are being treated for pneumonia in hospital, optimised treatments that achieve high cures rates while minimising lengths of hospital stay, side effects and resistance could have a major impact.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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