Intravenous and oral rehydration of children with severe malnutrition and gastroenteritis
| ISRCTN | ISRCTN76149273 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76149273 |
| Secondary identifying numbers | MRC Grant Refrence: MR/R018502/1 |
- Submission date
- 23/07/2018
- Registration date
- 08/08/2018
- Last edited
- 16/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Severe acute malnutrition (SAM) is a severe problem for African children. It can lead to the development of gastroenteritis, diarrhoea and dehydration, which leads to hospitalisation. However, on the current treatment recommended by the World Health Organization (WHO), the outcome is poor, with 20% of children dying during hospital admission.
A standard treatment for gastroenteritis, which leads to dehydration, is rehydration therapy, given by either an IV drip, which is used for more severe cases, or oral salt solutions, which is used for less severe cases or as a follow-on treatment after using a drip. The WHO guidelines for children with dehydration as a result of diarrhoea (which can be a complication of SAM, but also a result of bacterial or viral infections) recommend using oral salt solutions, with restricted use of intravenous drip therapy; however, this is controversial, as these recommendations are not based on results from clinical trials.
The aim of this study is to compare the recommended treatments for the rehydration of children with SAM with the standard treatments for the rehydration of children without SAM, to determine if these can be safely used for and improve the outcome of children with SAM.
Who can participate?
African children aged 6 months to 12 years who are hospitalised with SAM and have gastroenteritis leading to dehydration
What does the study involve?
For children with severe dehydration, we will compare the effects of giving them fluid via a drip, either quickly or slowly, with giving them the WHO SAM recommended regime, which involves using oral rehydration salts (ORS) and only starting drip treatment if the child goes into shock.
For children with less severe dehydration, we will compare the effects of using standard ORS treatment, which has a higher amount of sodium, with an ORS called ReSoMal (designed specifically for SAM), which has a lower sodium content.
What are the possible benefits and risks of participating?
The benefit of participating is that the children will be closely monitored throughout, so that any clinical deterioration can be identified at the earliest opportunity and appropriate therapy initiated. The possible risks of participating are:
1. Drip insertion and taking blood for laboratory tests may lead to pain, swelling or infection at the site of the drip; however, this will be minimised by careful technique and regular inspection
2. Liberal intravenous rehydration and salt-rich solution has the potential to cause malnourished hearts to go into pump failure or lead to harmful fluid accumulation
To minimise these risks, the nurses and doctors will monitor children very closely to look for side effects and if detected the treatments may be stopped. The trial sites in Africa have considerable experience with management of very ill children and this will serve minimise the risks to the patients in the trial
Where is the study run from?
KEMRI Wellcome Trust Research Programme (Kenya)
When is the study starting and how long is it expected to run for?
October 2018 to October 2024
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Ayub Mpoya
ampoya@kemri-wellcome.org
Contact information
Scientific
Wellcome Centre for Clinical Tropical Medicine
London
W2 1PG
United Kingdom
 ORCID ID |
0000-0002-0007-0645 |
|---|---|
| Phone | +254733411022 |
| kathryn.maitland@gmail.com |
Public
KEMRI Wellcome Trust Research Programme
Kilifi
-
United Kingdom
| Phone | +254 735 229 037 |
|---|---|
| EOguda@kemri-wellcome.org |
Study information
| Study design | Interventional open multi-centre phase II randomised controlled trial with a factorial design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN76149273_PIS_V3.0_21Oct2022.pdf |
| Scientific title | GASTROenteritis: Intravenous and oral rehydration of children with Severe Acute Malnutrition |
| Study acronym | GASTROSAM |
| Study hypothesis | For children with severe acute malnutrition (SAM) with severe dehydration due to diarrhoea, we hypothesize that standard intravenous regime WHO Plan C (100 ml/kg over 3-5 hours) used for non-SAM gastroenteritis with severe dehydration will result in better outcomes than the current very conservative SAM rehydration recommendations. In addition, we propose that the rate of rehydration may be critical and hypothesize that 100 ml/kg over 8 hours in SAM children will result in fewer fluid related adverse effects than rapid World Health Organization (WHO) Plan C guideline. We also propose that standard oral rehydration solutions (ORS) may be equally as effective with fewer side effects than low salt ReSoMal ORS recommended by WHO. |
| Ethics approval(s) | Imperial College Research Ethics committee (ICREC), 20/03/2018, 18IC4427 Mbale Regional Referral Hospital Research Ethics Committee, submitted for approval 17/07/2018 |
| Condition | Severe acute malnutrition |
| Intervention | Randomisation lists are generated and kept at the MRC CTU at UCL, London. The randomisation envelopes are prepared before the trial at the Clinical trials facility, KWTRP, Kilifi. These contain the actual allocation visible only once opened. The cards will be numbered consecutively and opened in numerical order. The trial includes 2 strata: Stratum A includes children with severe dehydration only. Children will be randomised in a 1:1:2 ratio to compare: 1. WHO Plan C arm: Rapid intravenous (IV) rehydration as per WHO Plan C (usually for non-SAM) children (100 ml/kg Ringers Lactate (RL) over 3-6 hours according to age including boluses (20 ml/kg) for those with shock (experimental)) 2. Slow Rehydration arm: A slower IV rehydration regimen (100 ml/kg RL given over 8 hours and no boluses (experimental)). 3. WHO SAM arm: rehydration regime involves no intravenous rehydration and rehydration with ReSomMal Oral rehydration solution (ORS) with IV boluses of RL only for children with shock (standard of care) Stratum B includes all children with some dehydration and all those with severe dehydration post IV rehydration, randomised in a 1:1 ratio to compare: 1. Standard WHO ORS given for non-SAM (experimental) versus 2. WHO SAM-recommended low-sodium ReSomMal The trial will run for a total of 18 months for both strata. |
| Intervention type | Mixed |
| Primary outcome measure | Current primary outcome measures as of 07/08/2023: 1. For the intravenous rehydration strategy, mortality at 96 h after enrolment 2. For the oral rehydration strategy, change in plasma sodium levels, measured by standard laboratory clinical chemistry analyser from baseline (time of enrolment) to 24 h after enrolment _____ Previous primary outcome measures: 1. For intravenous rehydration, urine output (ml/kg/hour) will be assessed as a surrogate marker of rehydration efficacy 8 hours after treatment 2. Change in plasma sodium levels, measured by standard laboratory clinical chemistry analyser at the baseline (time of enrolment) and after 24 hours |
| Secondary outcome measures | 1. Evidence of pulmonary oedema or heart failure during period of hospital admission: 1.1. Pulmonary oedema defined as developed of bilateral bi-basal crepitations of lungs on clinical examination 1.2. Heart failure defined as development of signs of severe tachycardia, elevated jugular venous pressure and de novo or increasing hepatomegaly 2. Changes in sodium from post-IV levels for those in Stratum A, measured using standard laboratory clinical chemistry analyser at the baseline and after intravenous rehydration is completed 3. Perturbations of electrolyte abnormalities (severe hyponatraemia < 125 mmol/l or hypokalaemia < 2.5 mol/l), measured by standard laboratory clinical chemistry analyser at the baseline and at any time during admission 4. Mid-upper arm circumference (MUAC) change, measured using MUAC tape (supplied by UNICEF) at the baseline and day 7 5. Survival at day 28 (child is confirmed to be alive at day 28) |
| Overall study start date | 20/07/2017 |
| Overall study end date | 31/10/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 60 Days |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | Children aged 272 children in the stratum with severe dehydration and an additional 64 children with some dehydration; overall 336 children |
| Participant inclusion criteria | Severe dehydration - Stratum A: 1. Aged 60 days to 12 years 2. Severe malnutrition defined as any of the following: Mid-upper arm circumference (MUAC) <11.5 cm, weight for height Zscore (< -3SD), or signs of kwashiorkor 3. Gastroenteritis, defined as > 3 loose stools per day 4. Signs of severe dehydration, defined (as per WHO definition) as at least one of the following: unable to drink, Alert Voice Pain Unresponsive scale (AVPU) < A, sunken eyes, reduced skin pinch (>2 seconds) or inability to take or retain oral fluids, and/or shock (defined as patient with cold peripheries, weak and fast pulse and capillary refill time > 3 seconds) Moderate/some dehydration - Stratum B: 1. Aged 60 days to 12 years 2. Severe acute malnutrition criteria, complicated by dehydrating diarrhoea (defined as > 3 loose stools per day) 3. Some to moderate dehydration or completing management of severe dehydration. Some to moderate dehydration defined as two of the following: restlessness, irritability, thirst, sunken eyes or skin pinch goes back slowly |
| Participant exclusion criteria | 1. Diarrhoea lasting more than 14 days 2. Known congenital or rheumatic heart disease 3. Refusal of consent |
| Recruitment start date | 02/09/2019 |
| Recruitment end date | 30/08/2024 |
Locations
Countries of recruitment
- Kenya
- Niger
- Nigeria
- Uganda
Study participating centres
P.O. Box 921
Mbale
-
Uganda
P.O. Box 289
Soroti
-
Uganda
PO Box 230
Kilifi
-
Kenya
Mombasa
-
Kenya
Kushari
Damboa Road
Maiduguri
-
Nigeria
Département de Magaria
Magaria
-
Niger
Département de Madarounfa
Maradi
-
Niger
Sponsor information
University/education
Joint Research Compliance Office, Room 221, Medical School Building, St Marys Campus
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +4420 7594 1188 |
|---|---|
| jrco@ic.ac.uk | |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Results will be published in peer review open access journals. The results from this trial will be disseminated locally through community meetings and national meetings with the wider healthcare professional community. These systems have been developed for dissemination of MRC FEAST trial results, and we plan to extend these with the ongoing TRACT trial and to this proposed trial (GASTROSAM). The lead investigators in Uganda will discuss with their Ministry of Health about the proposed trial. A summary or evidence brief will be produced to highlight the trial results and next steps required to inform rationale evidence-based guidelines. At that stage since the data generated from the study will not be immediate able to inform treatment guidelines rather it will generate new data, which will help inform the design of a larger Phase III trial. We have already had teleconferences with members of the epidemic consortium and WHO GOARN (Global Outbreak Alert and Response Network). We have shared systematic reviews we undertook in preparation of this trial. The current rehydration management guidelines for children with severe malnutrition are under intense speculation currently as a potential reason for the poor outcome in the current cholera epidemics. Through these connections will seek meetings with WHO, MSF and UNICEF and other international policy makers to discuss the results and subsequent trial plans. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 3.0 | 21/10/2022 | 15/04/2024 | No | Yes |
| Protocol file | version 3.0 | 19/10/2022 | 15/04/2024 | No | No |
| Statistical Analysis Plan | version 3.0 | 19/10/2022 | 15/04/2024 | No | No |
| Statistical Analysis Plan | version 4.0 | 17/12/2024 | 16/01/2025 | No | No |
Additional files
Editorial Notes
16/01/2025: The statistical analysis plan v4.0 was uploaded as an additional file.
15/04/2024: The protocol (not peer reviewed), statistical analysis plan and patient information sheet were uploaded as additional files.
07/08/2023: The following changes have been made:
1. The recruitment end date has been changed from 30/04/2023 to 30/08/2024.
2. The primary outcome measures have been changed.
3. The target number of participants has been changed from "Children aged 136 children in the stratum with severe dehydration and an additional 64 children with some dehydration; overall 200 children" to "Children aged 272 children in the stratum with severe dehydration and an additional 64 children with some dehydration; overall 336 children" and the target enrolment updated accordingly.
4. Mulago National Referral Hospital has been removed from the study participating centres and Kilifi County Hospital, Coast General Teaching Hospital, Nilefa Kiji MSF Hospital, Hôpital du district du Magaria and Hôpital de district de Madarounfa have been added.
5. Kenya, Niger and Nigeria have been added to the countries of recruitment.
03/05/2023: The public contact was updated.
11/04/2023: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/10/2023 to 31/10/2024.
2. The intention to publish date was changed from 30/04/2024 to 30/04/2025.
13/07/2022: Recruitment has been resumed.
12/07/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/09/2021 to 30/04/2023.
2. The overall trial end date has been changed from 31/12/2021 to 31/10/2023 and the plain English summary updated accordingly.
3. The intention to publish date has been changed from 30/06/2022 to 30/04/2024.
17/04/2020: Due to current public health guidance, recruitment for this study has been paused.
07/04/2020: The intention to publish date has been changed from 30/04/2021 to 30/06/2022.
06/04/2020: The following changes have been made:
1. The recruitment start date has been changed from 01/09/2018 to 02/09/2019.
2. The recruitment end date has been changed from 31/03/2020 to 30/09/2021.
3. The overall trial end date has been changed from 30/04/2020 to 31/12/2021.
4. The public contact has been chjanged.
09/08/2018: internal review
