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NCT ID: NCT03676764 Completed - Childhood Mortality Clinical Trials

Community Health Azithromycin Trial in Burkina Faso

CHAT
Start date: August 1, 2019
Phase: Phase 4
Study type: Interventional

An estimated 7.7 million pre-school aged children die each year, the majority from infectious diseases. Mass azithromycin distributions for trachoma may have the unintended benefit of reducing childhood mortality. We recently demonstrated the biannual mass azithromycin distribution significantly reduces all-cause child mortality in a cluster randomized trial (MORDOR I) conducted in three diverse regions of Sub-Saharan Africa. Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood morbidity and mortality. We propose a cluster randomized trial designed to repeat the original study to confirm the original results in a different geographic study with similarly high child mortality, and to better understand the mechanism behind any effect of azithromycin on child mortality. We hypothesize that biannual mass azithromycin distribution will reduce child mortality compared to placebo, and that this effect will be primarily driven by a reduction in infectious burden. Objectives: 1. Determine the efficacy of biannual mass azithromycin distribution versus placebo in children aged 1-59 months for reduction in all-cause mortality. 2. Determine the efficacy of targeted azithromycin distribution to infants during an early infant healthcare visit (approximately 5th through 12th week of life) on infant mortality. 3. Determine the mechanism behind the effect of biannual mass azithromycin distribution for reduction in child mortality. The study will be conducted in the Nouna District in northwestern Burkina Faso.

NCT ID: NCT03676751 Completed - Clinical trials for Resistance Bacterial

MORDOR II Burkina Faso: Longitudinal Trial

GAMIN
Start date: October 10, 2019
Phase: Phase 4
Study type: Interventional

Globally, childhood mortality has shown a promising downward trend in recent years, however, many sub-Saharan countries still have relatively high child mortality rates. In previous studies within Niger, Tanzania, and Malawi, mass azithromycin treatment to children aged 1-59 months old effectively reduced all-cause childhood mortality. A similar study will be conducted in Burkina Faso to replicate the results of mass azithromycin treatment. The investigators propose an individually randomized placebo-controlled trial alongside the MORDOR II Burkina Faso trial to evaluate the effect of a single dose of azithromycin (20 mg/kg) on potential mediators of the effect of azithromycin on all-cause mortality. Many questions surround the mechanism behind azithromycin's effect on reducing childhood mortality. Further questions exist regarding antibiotic resistance and how mass antibiotic administration can impact intestinal microflora. The goal of this study is to demonstrate the changes in the gut microbiome after antibiotic administration and to measure the growth of children after receiving a single dose of azithromycin. Additionally we will measure resistance markers, inflammatory markers, and IgA-bound bacteria. We hypothesize that a single dose of azithromycin will lead to a significant increase in child growth and that the gut microbiome will be significantly different in children who received azithromycin compared to those who received placebo. Objectives: 1. . To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on longitudinal changes in the intestinal microbiome over a 6-month period. We hypothesize that a single dose of azithromycin will result in a significant difference in the intestinal microbiome within the treatment group compared to the placebo group after a 6-month period within children ages 8 days-59 months. 2. . To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on child growth over a 6-month period. We hypothesize that a single dose of azithromycin will increase child growth over a 6-month period in children aged 8 days-59 months. 3. . To determine the effect of a single dose of azithromycin for children aged 8 days to 59 months on the presence of macrolide genetic resistance determinants within the first two weeks post-treatment. The investigators hypothesize that a single dose of azithromycin will increase the presence of macrolide resistance determinants over a 2 week period in children aged 8 days to 59 months. The study will be conducted in Nouna Town in northwestern Burkina Faso.

NCT ID: NCT03660839 Completed - Clinical trials for Plasmodium Falciparum Infection

Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

Start date: September 11, 2018
Phase: Phase 2
Study type: Interventional

Primary Objective: To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor. Secondary Objectives: - To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR. - To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR. - To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints. - To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone. - To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

NCT ID: NCT03614533 Completed - Typhoid Clinical Trials

Typhoid Conjugate Vaccine Trial Among Children Younger Than 2 Years in Ouagadougou, Burkina Faso

Start date: December 3, 2018
Phase: Phase 2
Study type: Interventional

Typhoid fever is an illness that may cause mild effects in children, such as fever and feeling tired, or it may cause serious effects-- even death. A new typhoid vaccine has recently been recommended by the World Health Organization (WHO) to prevent typhoid in children. But this new typhoid vaccine has not been tested with all of the vaccines given to children in Burkina Faso. The investigators want to look at this new vaccine, and study how safe it is in children in Burkina Faso and how their immune systems respond to the vaccine when given with other vaccines, such as yellow fever and meningitis A vaccines. The investigators plan to vaccinate 100 children between the ages of 9-11 months, and 150 children between the ages of 15 months and 2 years, in Ouagadougou, Burkina Faso, with either the typhoid vaccine or a vaccine against another illness called polio. Children will have follow-up visits on days 3, 7, 28 and 180. One teaspoon of blood will be collected on days 0 and 28.

NCT ID: NCT03568643 Completed - Clinical trials for Uncomplicated Severe Acute Malnutrition

Azithromycin for Uncomplicated Severe Acute Malnutrition in Burkina Faso (Pilot)

SAM
Start date: June 3, 2020
Phase: Phase 3
Study type: Interventional

This pilot study is a randomized controlled trial designed to test the effect of the administration of adjunctive azithromycin in conjunction with standard outpatient treatment for uncomplicated severe acute malnutrition (SAM) in children aged 6-59 months. Children presenting to nutritional programs in Burkina Faso who meet eligibility criteria will be randomized to a single dose of oral azithromycin or a 7-day course of amoxicillin (standard of care) upon admission into the program. All enrolled children will receive ready-to-use therapeutic foods (RUTF). Enrolled children will be followed at each weekly clinic follow-up visit up to 8 weeks following admission. Data on anthropometric indicators, vital status, and adverse events will be collected during follow-up. Nutritional recovery over the 8-week study period will be compared by arm.

NCT ID: NCT03533712 Completed - Prematurity Clinical Trials

Effect of a Fortified Balanced Energy-Protein Supplement on Birth Outcome and Child Growth in Houndé District, Burkina Faso.

MISAME-3
Start date: October 30, 2019
Phase: Phase 4
Study type: Interventional

The 2016 WHO antenatal care guidelines stated that pregnant women in undernourished populations should receive fortified balanced energy-protein (BEP) supplements to reduce the risk of stillbirth and small-for-gestational-age birth. However, acceptable supplements and delivery channels must be determined for different contexts. The present proposal therefore will 1) perform a formative study to identify the most suitable (acceptability and utilization) BEP supplement for pregnant women in rural Burkina Faso (phase 1) and 2) evaluate the efficacy of this supplement to improve birth weight, fetal and infant growth (phase 2). The nutritional composition of the BEP supplement was established during an expert convening at the BMGF in September 2016. Private sector partners will prepare the supplements in the selected forms with the recommended nutrient composition.

NCT ID: NCT03519503 Completed - Clinical trials for Growth and Development

Infant Peri-Exposure Prophylaxis to Prevent HIV-1 Transmission by Breastfeeding: Mechanisms & Safety

Start date: February 27, 2017
Phase:
Study type: Observational

General objective - To assess the long-term safety and efficacy of one-year infant prophylaxis using lamivudine (3TC) or lopinavir/ritonavir (LPV/r) to prevent post-natal transmission through breastfeeding. - To investigate the biological mechanisms involved in postnatal HIV transmission. Specific objectives - To compare the long-term safety of infant prophylaxis using either 3TC versus LPV/r on child development (growth, somatic and mental health), mortality, adrenal function, liver function, full blood count and mitochondrial toxicity. - To estimate the final efficacy data of 50 weeks of infant prophylaxis using either LPV/r or 3TC, since some mothers may have resumed breastfeeding after the trial. - To profile miRNA in breast milk according to maternal HIV status and HIV transmission. - To determine the influence of maternal milk on infant gut inflammation in an in vitro 3D-intestinal model (CACO-2 cells). The study population will comprise all ANRS 12174 PROMISE-PEP trial participants who completed the 50 week follow-up and are not HIV infected. An estimate of 881 mother-child pairs from the ANRS 12174 PROMISE- PEP will be recruited. This study is structured in two parts. The 'clinical & biological safety' component involves a cross sectional survey. A clinical and neuropsychological examination of participants will be conducted. In addition one venous blood sample will be collected to evaluate children HIV status, full blood count, liver & adrenal function and mitochondrial toxicity. Capillary hair follicles will be collected from 100 children in Zambia to study their genome integrity. The 'mechanisms' component includes biological assays to be conducted on breast milk samples previously collected from HIV infected, transmitting or non-infected mothers enrolled at ANRS 12174 PROMISE-PEP trial. Primary endpoint: Long term survival, mortality rate, measurements of infant growth (length and weight), somatic and neuropsychological development of the 5 year old children enrolled in the ANRS 12174 PROMISE- PEP trial. Secondary endpoints: HIV seroconversion since last PROMISE PEP trial visit, full blood count, liver function, adrenal function, serum lactate. Number of mitochondrial DNA copies per cell & percentage of mitochondrial DNA deletion for mitochondrial toxicity. Number of micronuclei & number of Ɣ-tubulin spot per cell to study genomic toxicity.

NCT ID: NCT03459157 Completed - HIV/AIDS Clinical Trials

Access to PrEP for MSM: Acceptability and Feasibility in Community-based Clinics in West Africa (CohMSM-PrEP)

CohMSM-PrEP
Start date: November 20, 2017
Phase: N/A
Study type: Interventional

This demonstration project will assess the acceptability and feasibility of pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) as part of a comprehensive HIV prevention package in community-based clinics in West Africa. An interventional, open label, multidisciplinary and multicentre cohort study will be performed in Burkina Faso, Côte d'Ivoire, Mali, and Togo. All MSM enrolled will benefit from a comprehensive HIV prevention package including quarterly clinical examinations, screening and treatment of STIs, screening of HIV, PrEP (daily or on-demand, according the participant's choice), immunisation against hepatitis B, individualised peer-led support (for adherence and prevention), group discussions, condoms, and lubricants.

NCT ID: NCT03400930 Completed - Clinical trials for Severe Acute Malnutrition

Biomedical Investigations for Optimized Diagnosis and Monitoring of Severe Acute Malnutrition (SAM): Elucidating the Heterogeneous Diagnosis of SAM by Current Anthropometric Criteria and Moving Beyond

OptiDiag
Start date: January 1, 2017
Phase:
Study type: Observational

INTRODUCTION In 2014, 50 million children under 5 suffered from acute malnutrition, of which 16 million suffered from SAM, most of them living in sub-Saharan Africa and Southeast Asia. SAM children have higher risk of mortality (relative risk between 5 and 20). It is an underlying factor in over 50% of the 10 - 11 million preventable deaths per year among children under five. At present, 65 countries have implemented WHO recommendations for SAM treatment (both in-patient for complicated cases and outpatient for uncomplicated cases) but these programs have very low coverage, reaching only around 10 - 15 % of SAM children. In 2009 the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) issued a joint statement in an effort to harmonize the application of anthropometric criteria for SAM diagnosis and monitoring in child aged 6 - 59 months; the statement presents recommended cut-offs, and summarizes the rational for the adoption, of the following two anthropometric criteria: 1. Weight-for-Height Z-Score (WHZ): "WHO and UNICEF recommend the use of a cut-off for weight-for-height of below -3 standard deviations (SD) of the WHO standards to identify infants and children as having SAM." Additionally, analysis of existing data show that children with a WHZ < -3 have a highly elevated risk of death. 2. Mid-Upper Arm Circumference (MUAC): "WHO standards for the MUAC-for-age show that in a well-nourished population there are very few children aged 6 - 59 months with a MUAC less than 115 mm. Children with a MUAC less than 115 mm have a highly elevated risk of death compared to those who are above. Thus it is recommended to [use] the cut-off point [of] 115 mm to define SAM with MUAC." GENERAL OBJECTIVE To generate new evidence on pathophysiological process, nutritional needs and risks associated with different types of anthropometric deficits in children under 5, in order to optimize the diagnosis and treatment of SAM. SPECIFIC OBJECTIVES - To compare nutritional status, metabolism, pathophysiological process and risks in different types of SAM anthropometric diagnosis, with or without concomitant stunting (growth retardation). - To analyze the extent to which current SAM treatment is promoting recovery and healthy growth in different categories of children. - To evaluate the relevance of current discharge criteria used in nutrition programs and their association with metabolic recovery, in different age groups and among those who are stunted. - To test novel rapid tests of emerging biomarkers predicting long-term outcomes and mortality risk in the field. METHODOLOGY A wide range of supplementary information related to nutritional status, body composition, metabolic and immune status, including emerging biomarkers of metabolic deprivation and vulnerability, will be collected besides anthropometry during prospective observational studies. They will be collected with minimum level of invasiveness, compatible with field work requirements in the humanitarian context. Phase 1: Cross-sectional surveys. Phase 2: Prospective cohort studies involving SAM children between 6 months and 5 years old. Children admitted as SAM at the nutrition centers will be enrolled into the cohort. The follow up duration will be at least three months. EXPECTED OUTCOMES - Confirmation of current hypotheses related to: 1. possible misdiagnosis of SAM made by MUAC or WHZ criteria, 2. varying degree of severity and need for admission to treatment of the different types of diagnosis, 3. underlying heterogeneity of the pathophysiology. - Generation of new algorithms for the assessment and classification of malnourished children, based on the combined use of emerging biomarkers and anthropometric measures, or on the modification of anthropometric criteria. - Generation of new treatment paradigms based on the predictive value of biomarkers in combination with traditional anthropometric measures. This will enable us to assess the power of current treatment regimens to promote long-term weight gain and growth and will allow us to tailor treatment to the physiological needs of the child.

NCT ID: NCT03199547 Completed - Neonatal SEPSIS Clinical Trials

Pre-delivery Administration of Azithromycin to Prevent Neonatal Sepsis & Death

PregnAnZI-2
Start date: October 21, 2017
Phase: Phase 3
Study type: Interventional

Though maternal and neonatal health are high priority areas for international development, maternal and neonatal mortality remain unacceptably high. Worldwide there are 1 million maternal and 4 million neonatal deaths every year and half of them occur in sub-Saharan Africa. Post-partum and neonatal severe bacterial infections, namely sepsis, are leading causes of maternal and neonatal deaths in sub-Saharan Africa. Newborns can be infected during labour - when passing through the birth canal - and also during the first days/weeks of life, as a consequence of the close physical contact with the mother, when the latter carriers bacteria. As the mother is an important source of bacterial transmission to the newborn, treating mothers with antibiotics during labour should decrease their bacterial carriage and therefore lower transmission to the newborn. As carriage is a necessary step towards severe disease, this intervention should in turn result in the lower occurrence of severe bacterial disease and mortality during the neonatal period. In many high-income countries, pregnant women are screened during pregnancy for vaginal carriage of Group B Streptococcus, the bacteria responsible for the vast majority of neonatal sepsis in the developed world. If women are carriers, they are treated with intravenous antibiotics during labour to decrease the risk of severe disease to their off-spring. Although this intervention has been successful in developed countries, infrastructure and resource limitations in regions like sub-Saharan Africa prevent both screening and use of intravenous antibiotics. Also, in Africa several bacterial pathogens are responsible for neonatal sepsis and the antibiotics needed in the continent should cover a wider number of bacteria; and ideally cover also bacteria responsible for severe post-partum disease in the mother. We will conduct a large trial in West Africa, The Gambia and Burkina Faso, with the main objective of determining if a single dose of an oral antibiotic given to women during labour decreases newborn mortality. The trial will also assess the effect of the antibiotic on lowering newborns and maternal hospitalization during the first week's post-partum. We have selected an antibiotic (azithromycin) that in sub-Saharan Africa has already been used for elimination of other prevalent diseases such as trachoma. This antibiotic is safe, requires a single oral administration, has no special storage requirements and has the potential to eliminate most of the bacteria commonly causing severe disease in newborns and post-partum women in the continent. Very important this antibiotic is not widely used in clinical care in the continent, and therefore, any temporal increase of resistance induced by the intervention should not have implications on current treatment guidelines. Before going to the large trial proposed here (12,000 women to be recruited), we have generated robust preliminary data on the effect of the intervention in a proof-of-concept trial conducted in The Gambia (829 women and their offspring recruited). We found that in fact, babies born from mothers who had taken this antibiotic during labour were less likely to carry bacteria that can potentially cause severe disease. These babies were also three times less likely to have bacterial skin infections or umbilical infections, both highly common among African newborns. Besides, fever or mastitis (again both very common in the region) during the post-partum period were four times lower among mothers who had taken the antibiotic during labour. Such trial confirmed our hypothesis of impact on bacterial transmission but it was too small to assess the effect of the antibiotic on mortality and hospitalizations. The preliminary trial also showed that women from the azithromycin group were less likely to need antibiotics for treatment infections during the puerperal period, decreasing then the pressure on the scarcity of antibiotics available in the continent. The advantages of our approach are its simplicity, low cost and the possibility of protecting both mothers and babies with the same intervention.