GASTRO

COMPLETED STUDY:

GASTRO

GASTRO

Research Details

  • Detailed study information

    Full study title

    Gastroenteritis Aggressive Versus Slow Treatment for Rehydration (GASTRO): A Phase II Rehydration Trial for Severe Dehydration—WHO Plan C Versus Slow Rehydration

    Study overview

    Acute gastroenteritis can cause substantial losses of water and electrolytes through diarrhoea and vomiting. Without timely treatment, affected children may develop severe dehydration, circulatory failure, organ dysfunction or death.

    The World Health Organization’s Plan C recommends rapid intravenous rehydration for children with severe dehydration. However, before the GASTRO Study, the safety and effectiveness of this strategy had not been formally evaluated in a randomised clinical trial in African hospitals.

    Concerns about rapid fluid administration had also increased following the FEAST trial, which found that fluid boluses increased mortality among children with severe infections and impaired circulation. GASTRO therefore compared the standard WHO Plan C regimen with a simpler and slower intravenous rehydration strategy.

    Study objectives

    The study aimed to:

    • Compare the safety of rapid and slow intravenous rehydration in children with severe dehydration caused by gastroenteritis.
    • Determine whether a slower eight-hour regimen increased serious adverse events.
    • Compare the speed of recovery from clinical signs of dehydration.
    • Assess the effects of the two strategies on cardiovascular, respiratory and neurological outcomes.
    • Evaluate how easily the treatment protocols could be implemented in resource-limited hospitals.
    • Generate evidence for the design of larger clinical trials of childhood rehydration.

    Study design

    GASTRO was a multicentre, open-label, Phase II randomised controlled trial.

    A total of 122 children were enrolled and randomly assigned to one of two intravenous rehydration strategies:

    • Standard WHO Plan C rehydration; or
    • Slower intravenous rehydration over eight hours.

    The study originally planned to enrol approximately 120 participants and ultimately recruited 122 children. The primary analysis compared serious adverse events occurring during the first 48 hours after randomisation. BMC Medicine

    Study population

    Participants were children who:

    • Were aged between 2 months and 12 years.
    • Were admitted to hospital with acute gastroenteritis.
    • Had diarrhoea, with or without vomiting.
    • Had clinical signs of severe dehydration.
    • Required intravenous rehydration.

    Unlike the subsequent GASTROSAM trial, GASTRO focused on children with severe dehydration who did not have severe acute malnutrition.

    Study locations

    The study was conducted at hospitals in Uganda and Kenya, including:

    • Mbale Regional Referral Hospital, Uganda
    • Soroti Regional Referral Hospital, Uganda
    • Kilifi County Hospital, Kenya

    Mbale Clinical Research Institute supported the implementation of the Ugandan component of the study.

    Study interventions

    WHO Plan C rehydration

    Children allocated to WHO Plan C received Ringer’s lactate at a total volume of 100 ml/kg:

    • Over three hours for children aged one year or older.
    • Over six hours for infants younger than one year.

    The protocol also permitted 0.9% saline boluses for children who met the study criteria for shock.

    Slow rehydration

    Children allocated to the experimental strategy received:

    • Ringer’s lactate at a total volume of 100 ml/kg.
    • Administration over eight hours, irrespective of age.
    • No additional rapid fluid boluses.

    After completing intravenous rehydration, children continued to receive oral fluids and routine clinical care as appropriate.

    Main outcomes assessed

    The primary outcome was the occurrence of serious adverse events within 48 hours, including:

    • Cardiovascular complications
    • Respiratory complications
    • Neurological complications
    • Fluid-overload events
    • Death

    Secondary outcomes included:

    • Resolution of clinical signs of dehydration.
    • Time taken for the child to tolerate oral fluids.
    • Time to hospital discharge.
    • Urine output.
    • Changes in body weight.
    • Electrolyte abnormalities.
    • Requirement for additional treatment.
    • Cardiac biomarkers associated with cardiac strain or injury.
    • Practical adherence to the two rehydration protocols.

    Key findings

    The study found that slower rehydration over eight hours was as safe as WHO Plan C.

    Important findings included:

    • Serious adverse events were similar between the two treatment groups.
    • Four children died during the study—two in each treatment group.
    • There was no evidence that the slower regimen increased fluid overload, cardiovascular complications or other serious adverse events.
    • Both strategies produced similar resolution of dehydration.
    • The time taken to tolerate oral fluids was similar between the groups.
    • Length of hospital stay was also comparable.
    • The slower protocol was simpler for healthcare workers to implement.
    • The two-step WHO Plan C regimen required continuing staff training to maintain correct implementation.

    The investigators concluded that slower rehydration using 100 ml/kg of Ringer’s lactate over eight hours appeared safe and was easier to implement than the standard age-dependent Plan C regimen. However, the trial was not large enough to establish whether either treatment reduced mortality. PubMed

    Importance of the study

    GASTRO was among the first randomised trials to formally evaluate WHO Plan C against an alternative intravenous rehydration strategy in African children with severe dehydration.

    The study demonstrated that a simpler eight-hour regimen could achieve similar clinical outcomes without increasing serious adverse events. A uniform regimen that does not change according to age may also be easier for healthcare workers to administer correctly, particularly in busy or resource-limited hospitals.

    The study generated essential feasibility and safety evidence for larger trials. It also helped inform the design of the later GASTROSAM trial, which investigated oral and intravenous rehydration in children with severe acute malnutrition.

    Study leadership and collaborators

    The research team included investigators from:

    • Mbale Clinical Research Institute
    • Mbale Regional Referral Hospital
    • Soroti Regional Referral Hospital
    • KEMRI–Wellcome Trust Research Programme
    • Imperial College London
    • MRC Clinical Trials Unit at University College London
    • University Hospital of Wales

    Key investigators included:

    • Professor Kathryn Maitland
    • Professor Peter Olupot-Olupot
    • Dr Kirsty Houston
    • Jack Gibb
    • Margaret Nakuya
    • Rita Muhindo
    • Dr Nchafatso Obonyo
    • Ayub Mpoya
    • Professor Diana Gibb
    • Elizabeth George
    • Roisin Connon
    • Jennifer Evans
    • Sophie Uyoga

    Professor Peter Olupot-Olupot led and supervised the study activities undertaken through Mbale Clinical Research Institute and Mbale Regional Referral Hospital.

    Funding

    The research was supported through Wellcome-funded clinical research programmes and fellowships, including grants associated with Imperial College London and the KEMRI–Wellcome Trust Research Programme.

    The publication reports support through Wellcome grant references including:

    • 105603/Z/14/Z
    • 100693/Z/12/Z
    • 097816/Z/11/A

    Ethics and trial registration

    The study received ethics and regulatory approval from the relevant committees and national authorities in Uganda, Kenya and the United Kingdom.

    The Imperial College Research Ethics Committee reference was:

    • ICREC 16IC3388

    The study was registered as:

    Parents or legal guardians provided informed consent before children were enrolled.

    Study status

    Completed

    The study completed participant recruitment and follow-up before publication of its principal findings in July 2019.

    Selected publications

    1. Houston KA, Gibb JG, Olupot-Olupot P, et al. Gastroenteritis Aggressive Versus Slow Treatment for Rehydration (GASTRO): A Phase II Rehydration Trial for Severe Dehydration—WHO Plan C Versus Slow Rehydration. BMC Medicine. 2019;17:122. Read the publication
    2. Houston KA, Gibb JG, Mpoya A, et al. Gastroenteritis Aggressive Versus Slow Treatment for Rehydration (GASTRO): A Pilot Rehydration Study for Severe Dehydration—WHO Plan C Versus Slower Rehydration. Wellcome Open Research. 2017;2:62. Read the study protocol

Study Summary

GASTRO Study – Gastroenteritis Aggressive Versus Slow Treatment for Rehydration

The GASTRO Study investigated whether slower intravenous rehydration could be safely used in children with severe dehydration caused by gastroenteritis. The Phase II trial enrolled 122 children at hospitals in Uganda and Kenya, including Mbale Regional Referral Hospital. It compared standard WHO Plan C rehydration with an eight-hour regimen using 100 mL/kg of Ringer’s lactate. Serious adverse events, mortality and recovery from dehydration were similar between groups. The study found that slower rehydration appeared safe and was simpler to implement, providing important evidence for larger trials and informing subsequent research on rehydration in severely malnourished children.

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.