FLACSAM

COMPLETED STUDY:

FLACSAM

FLACSAM

Research Details

  • FLACSAM Study

    Full title

    First-Line Antimicrobials in Children with Complicated Severe Acute Malnutrition

    Study overview

    Children with complicated severe acute malnutrition are at particularly high risk of severe bacterial infection and death. Although international treatment guidelines recommend routine antibiotics alongside nutritional rehabilitation, there has been limited evidence about the most effective antibiotic regimen for these children.

    The FLACSAM Study was designed to determine whether alternative first-line antibiotic treatments could reduce mortality and improve nutritional recovery among children admitted to hospital with complicated severe acute malnutrition. It also investigated antimicrobial resistance, medicine dosing, treatment safety and healthcare costs.

    Study objectives

    The primary objective was to compare the effectiveness of different first-line antibiotic regimens in children hospitalised with complicated severe acute malnutrition.

    The study specifically aimed to:

    • Determine whether ceftriaxone improves survival compared with standard antibiotic treatment.
    • Assess whether adding metronidazole provides additional clinical benefit.
    • Compare nutritional recovery between treatment groups.
    • Evaluate the safety and tolerability of the study medicines.
    • Investigate antimicrobial resistance among participating children.
    • Establish appropriate ceftriaxone and metronidazole dosing for severely malnourished children.
    • Compare the healthcare and treatment costs associated with the antibiotic regimens.

    Study design

    FLACSAM was designed as a multicentre, randomised clinical trial using a two-by-two factorial design. This design allowed the researchers to assess two treatment comparisons within the same trial:

    • Ceftriaxone versus standard treatment: Ceftriaxone was compared with the standard penicillin or ampicillin plus gentamicin regimen.
    • Metronidazole versus no metronidazole: Participants were also assigned to receive either metronidazole or no metronidazole.

    Participants were followed after hospital admission to assess survival, nutritional recovery, readmission and other clinical outcomes.

    Study population

    The study enrolled children aged approximately two months to 13 years who were admitted to hospital with complicated severe acute malnutrition.

    Children required inpatient treatment because they had severe malnutrition accompanied by medical complications such as infection, poor appetite, diarrhoea, dehydration or other serious illnesses. A comparison group of hospitalised children without severe acute malnutrition was also included in parts of the antimicrobial-resistance investigation.

    Study sites

    The FLACSAM Study was implemented at hospitals in Kenya and Uganda, including:

    • Mbale Regional Referral Hospital, Uganda
    • Kilifi County Hospital, Kenya
    • Coast General Teaching and Referral Hospital, Mombasa, Kenya
    • Mbagathi Hospital, Nairobi, Kenya

    The Mbale site contributed experience from a busy regional referral hospital serving children from eastern Uganda and neighbouring areas.

    Study interventions

    Participants received one of the antibiotic combinations determined through random allocation.

    Standard antibiotic treatment

    The standard treatment consisted of penicillin or ampicillin combined with gentamicin, in accordance with existing treatment guidelines for children with complicated severe acute malnutrition.

    Ceftriaxone

    Ceftriaxone was evaluated as an alternative broad-spectrum antibiotic. It can be administered once daily and may offer improved activity against some bacteria that are resistant to standard first-line antibiotics.

    Metronidazole

    The study also investigated whether adding metronidazole improved outcomes by treating anaerobic bacteria and possible bacterial overgrowth in the gastrointestinal tract. Potential benefits were assessed alongside possible adverse effects such as nausea, reduced appetite and medicine intolerance.

    Outcomes assessed

    The study evaluated several important clinical and health-system outcomes, including:

    • Mortality during hospitalisation and follow-up
    • Nutritional recovery
    • Weight gain and improvement in nutritional status
    • Length of hospital stay
    • Hospital readmission
    • Treatment failure
    • Adverse reactions to the study medicines
    • Antimicrobial resistance
    • Acquisition of hospital-associated infections
    • Medicine and healthcare costs

    Follow-up assessments were planned at key points after enrolment, including approximately days 14, 45 and 90.

    Pharmacokinetic component

    A pharmacokinetic study was conducted to determine suitable doses of ceftriaxone and metronidazole for severely malnourished children. Severe malnutrition can alter how medicines are absorbed, distributed and removed from the body.

    The pharmacokinetic analysis included 81 children aged two to 45 months. The modelling supported doses of approximately 80 mg/kg once daily for ceftriaxone and 12.5 mg/kg twice daily for metronidazole. These findings helped inform dosing in the main clinical trial. Read the published pharmacokinetic study.

    Antimicrobial-resistance component

    Antimicrobial resistance was an important part of FLACSAM. The study assessed whether bacteria carried by participating children were susceptible to the antibiotics recommended for routine treatment.

    It also examined whether receiving broad-spectrum antibiotics such as ceftriaxone increased the acquisition or carriage of antibiotic-resistant organisms. This information is important for balancing the immediate treatment needs of severely ill children against the longer-term risks of antimicrobial resistance.

    Importance of the study

    Severe acute malnutrition remains a major cause of illness and death among children in sub-Saharan Africa. Children admitted with complicated malnutrition often have serious infections, but the antibiotics recommended in existing guidelines may not be effective against all locally circulating bacteria.

    FLACSAM was intended to provide evidence for improving hospital treatment guidelines, reducing preventable deaths and promoting responsible antibiotic use. Its findings are relevant to clinicians, hospitals, national health programmes and organisations developing international child-health and nutrition guidelines.

    Sponsor and funding

    The study was sponsored by the University of Oxford and supported through the Joint Global Health Trials Scheme, involving the UK Medical Research Council, the UK Department for International Development and the Wellcome Trust.

    Further project and funding information is available through the UKRI Gateway to Research.

    Study registration and ethical oversight

    The study was registered under:

    Ethical approval included review by the relevant national and institutional research ethics committees. The Kenyan approvals included KEMRI Scientific and Ethics Review Unit reference KEMRI/SERU/CGMR-C/063/3399, while the University of Oxford approval was issued under OxTREC reference 1-17. In Uganda, the Mbale Regional Referral Hospital research and Ethics Committee, the Uganda National Council of Science and Technology and The National Drug Authority approved the study.

    Study status and results

    The preparatory pharmacokinetic findings have been published, and preliminary study findings were presented at scientific meetings. The study was closed in 2021.

Study Summary

  • FLACSAM Study

    • Purpose: Compared first-line antibiotic treatments for children hospitalised with complicated severe acute malnutrition.
    • Participants: Children aged approximately 2 months–13 years.
    • Sites: Mbale, Uganda, and hospitals in Kenya.
    • Interventions: Compared ceftriaxone with standard antibiotics and assessed the addition of metronidazole.
    • Key focus: Survival, nutritional recovery, safety, antimicrobial resistance and treatment costs.
    • Significance: Generated evidence to inform antibiotic treatment guidelines and promote responsible antimicrobial use.
    • Status: Completed in 2021.

About

Ms. Adyango Catherine is a Human Resource Manager and Senior Grants Professional with over 15 years of experience in managing multimillion-dollar donor portfolios, project operations, and organizational systems strengthening. She currently serves as Human resource Manager at Mbale Clinical Research Institute (MCRI), where she leads in Human resource management,  donor compliance, project operations, and institutional capacity building.

At MCRI, Catherine has combined her expertise in grant management and human resources to establish efficient systems that support both research and staff welfare. She played a pivotal role in championing organizational culture reforms, developing HR policies, strengthening staff welfare schemes, and promoting inclusive recruitment processes. She also streamlined adoption of a Human Resource Management Information System (HRMIS/ESS), which reduced administrative bottlenecks and improved efficiency across teams.

Her academic background includes a Postgraduate Diploma in Human Resource Management (Uganda Management Institute), an MSc in Health Services Management, and a bachelor’s degree in business administration & management. Catherine is also pursuing ACCA training, demonstrating her commitment to continuous professional growth.

Catherine’s career reflects a strong commitment to strategic leadership, staff development, and inclusive programming, with a proven ability to balance donor expectations and human resource needs. Her work at MCRI has significantly contributed to building sustainable research capacity, enhancing compliance systems, and creating a supportive work environment that empowers both researchers and administrative staff.

About

Denis Amorut serves as the Study Site Coordinator at the Mbale Clinical Research Institute’s Soroti Site. He is a qualified Registered Nurse with a Bachelor of Science in Health Services Management from the Islamic University in Uganda and a Diploma in Comprehensive Nursing from Soroti School of Registered Comprehensive Nursing. Additionally, he is currently pursuing an Advanced Postgraduate Diploma in Clinical Research & Quality Assurance at James Lind Institute, showcasing his commitment to advancing his expertise in clinical research. Denis has an extensive professional background with 12 years in clinical nursing practice and 11 years dedicated to clinical research. He is registered with the Uganda Midwives and Nurses Council, highlighting his professional standing in the healthcare sector.
 
Throughout his career, Denis has held significant positions such as Trial Manager since November 2021 and previously as Study Site Coordinator at Soroti Regional Referral and Teaching Hospital from 2008 to October 2021. He also serves as a member of the Medicine and Therapeutic Committee at the same hospital since 2018. Denis has enriched his knowledge and skills through numerous online courses and certifications in areas like research ethics, data management for clinical studies, Good Clinical Practice (GCP), and managing health emergencies like Covid-19. His involvement in various research studies, including the TRACT study, and his roles in hospital committees further demonstrate his dedication to both practice and research in healthcare, focusing on improving patient care through evidence-based practices.

About

Ms. Linda Isabirye serves as the Public and Community Engagement Officer at MCRI, where her role encompasses a variety of tasks aimed at enhancing the Institute’s interaction with both internal and external communities. Her work is divided into two primary focuses: public engagement, where she communicates the Institute’s research and ideas to the public, and community engagement, where she assists others in conducting research and achieving their objectives.

In her community engagement efforts, Linda is involved in developing and sustaining a public engagement and involvement framework for the research program. She identifies local opportunities for community collaboration, nurturing relationships with MCRI’s research scientists, staff, and the broader community.

With over two years of experience, she has worked extensively with diverse community stakeholders. Her responsibilities include coordinating activities for the Community Advisory Board (CAB), designing, and overseeing the execution of Community Engagement (CE) initiatives. These initiatives are crucial for identifying, recruiting, and retaining volunteers, engaging community leadership, and supporting the formation and operation of community peer groups. This includes working with study participants, family support groups, and youth and adolescent groups, among others.

About

Rita Muhindo holds a MSc. Molecular Biology from Staffordshire University, UK. She attained her BSc. Biomedical Laboratory Science and Technology degree from Makerere University and an Advanced Diploma in Health Services Management from Islamic University in Uganda. She joined Mbale Clinical Research Institute in July 2011 as a laboratory technologist participating in setting up various laboratory assays for all clinical trials at the MCRI.

She is currently the laboratory manager of MCRI, a role which involves supervision all laboratory research activities at MCRI main and satellite laboratories. She has over twelve years of experience in managing laboratory clinical research and diagnostics service delivery across several key disciplines including molecular, immunology, hematology, microbiology and clinical chemistry.

She has keen interest in understanding the prevalence of red cell polymorphisms present in Ugandan donor populations. Her main focus of her MSc project was on the prevalence of Glucose-6-Phosphate dehydrogenase deficiency, α-thalassaemia and Haemoglobin S among Ugandan donors. Rita is also keen to explore the effects of these polymorphisms on the resolution of severe anaemia.

About

Dr. Charles Benard Okalebo is a highly qualified professional with a B. Pharm, an MPH, and currently a fellow in Infectious Disease and Field Epidemiology under the EDCTP-funded IDEA fellowship. His background as a pharmacist and public health specialist, combined with his role as a Quality Assurance Officer, has provided him with extensive experience in clinical research. This diverse training has honed his skills in assessing healthcare gaps, identifying problems, and designing projects to address these deficiencies. Dr. Okalebo values accuracy, integrity, quality, and career growth above all.
 
He is an experienced and determined professional in conducting clinical trials for both infectious and non-infectious diseases. With eight years in the research field, he has served as a Pharmacist and Quality Assurance Officer at the Mbale Clinical Research Institute, focusing on various types of clinical trials related to infectious diseases. His involvement spans across all phases of clinical trials (I-III), including protocol design, review, and implementation; navigating regulatory approval processes; managing investigational medicinal products (IMP); monitoring studies; establishing and implementing Quality Management processes; pharmacovigilance; and leading training sessions on the ethical conduct of research. The trials he has participated in include TRACT (ISRCTN84086586), GASTROSAM (ISRCTN76149273), PAC (ISRCTN11594437), FLACSAM (ISRCTN18051843), MIMBLE (ISRCTN10309022), and TABS (ISRCTN49726849) studies.
 
Dr. Okalebo is a dedicated researcher with a keen interest in advancing his career in pharmaco-epidemiology, statistics, and pharmacovigilance.

About

Felix Opio joined the Mbale Clinical Research Institute (MCRI) in April 2014 as Data Manager under the REACH (Realizing Effectiveness Across Continents with Hydroxyurea) ClinicalTrials.gov NCT01966731) which is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, long-term risks and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries (Mable Uganda,Kilifi Kenya, Luanda Angola and Kinshasa DRC).

He holds a Bachelor of Science in Computer Science from Gulu University, a post graduate diploma in Monitoring and Evaluation from Uganda Management Institute (UMI), Certificate in Project Management Professional from Devimpact Institute Kenya and various other certification in Clinical database development.

He Has 9 years of experience in Clinical Database design and Management, He is Currently overseeing data management work for the REACH study and all the day to day activities of the Project, He is also a member of the internal Clinical Trial Monitoring Unit and A chairperson Procurement Committee for Mbale Clinical Research Institute.

About

Ebitu Caleb Daniel serves as an I.T Support Officer at the Mbale Clinical Research Institute. He is recognized as an accomplished network and systems administrator, who takes pleasure in applying his skills to support and contribute to the technological advancement of research within the institution.
 
Ebitu graduated from Uganda Christian University Mukono with a Bachelor’s degree in Computer Science. Over the years, he has also acquired various certifications including CCNA, Information Security, Google Cloud Developer, PMP (Telecom), and Federated Identity Management.

About

Laban has accumulated over four years of experience in managing research financial processes since joining the Mbale Clinical Research Institute on July 1, 2019, as an Accounts Assistant. This experience complements his extensive background of over ten years in the banking sector, where he has previously worked for two banks in roles involving people management, cash management, internal controls, and accountability.

He holds a Bachelor’s degree in Business Studies, specializing in Accounting, from the Islamic University of Uganda. He is currently pursuing a Certificate of Public Accountants (CPA) from the Institute of Certified Public Accountants of Uganda (ICPAU), with only two papers remaining to complete the course.

Driven by an ambition to advance his career in accounting and expand his experience in research-related accounting managed by well-established systems and processes, he believes that MCRI is the ideal place for his professional growth.