SEPSISPhase 2/3PB-SAMNCT04542473
Pancreatic Enzymes and Bile Acids in Acutely Ill Severely Malnourished Children
A Phase 2/3 study testing Pancreatic Enzyme and Ursodeoxycholic acid in people with SEPSIS and MALNUTRITION, CHILD, run by University of Oxford at 4 sites in 4 countries.
Trial summary
Children with severe malnutrition who are sick and admitted to hospitals have high mortality, usually because of infection. Malnourished children have more potentially harmful bacteria in their upper intestines than well-nourished children and this may contribute to inflammation in the gut and whole body. Read more about this study
- Who is it for?
- Ages 2 to 59 months
- Conditions the study is for
- SEPSIS, MALNUTRITION, CHILD
- What is being tested?
- Pancreatic Enzyme and Ursodeoxycholic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 1 Jul 2021to 30 Jun 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 2 to <59 months
- Admitted to hospital with an acute, non-traumatic illness and within 72 hours of admission at the time of enrolment
- Severe malnutrition (weight-for-height <-3 z scores of the median WHO growth standards and/or mid upper arm circumference <115mm (<110mm age below 6 months), or symmetrical oedema of at least the feet related to malnutrition (not related to a primary cardiac or renal disorder)
- Able to feed orally in usual state of health.
- Accompanied by care provider who provides written informed consent
- Primary caregiver plans to stay in the study area during the duration of the study
- Presence of two or more features of severity as specified below. If a child meets two criteria, they may be enrolled before further criteria are assessed (e.g. a child may be eligible on clinical signs before the complete blood count results are known):
- Respiratory distress "Subcostal indrawing" or "nasal flaring" or "head-nodding" Oxygenation "Central cyanosis" or SaO2 <90% Circulation Limb temperature gradient or capillary refill >3 seconds Conscious level AVPU < "A" Pulse > 180 per min Haemoglobin < 7g/dl Blood glucose < 3mmol/L White blood cells < 4 or > 17.5 x 109/L Temperature <36 or >38.5oC Very low MUAC MUAC <11cm
Who cannot join
None listed.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: Pancreatic Enzymes and Bile Acids: A Non-Antibiotic Approach to Treat Intestinal Dysbiosis in Acutely Ill Severely Malnourished Children
Children with severe malnutrition who are sick and admitted to hospitals have high mortality, usually because of infection. Malnourished children have more potentially harmful bacteria in their upper intestines than well-nourished children and this may contribute to inflammation in the gut and whole body. These bacteria may cross from the intestines to the bloodstream causing life-threatening infections. A related abnormality among malnourished children is reduction in the digestive enzymes made by the pancreas and the liver. Apart from helping with digestion of food, these enzymes are important in helping the body control bacteria in the upper intestines. It is therefore possible that treatment with digestive enzymes could help reduce the burden of harmful bacteria and thus lower inflammation and the risk of serious infection. One study conducted in Malawi has shown that children with severe malnutrition who were supplemented with pancreatic enzymes had a lower risk of dying. However, this was a small study and although promising, requires validation. No studies of supplementation with bile acids have been done among severely malnourished children. However, bile acids are commonly used to manage patients with liver function abnormalities, something that malnourished children suffer from as well. The investigators want to find out if supplementing these pancreatic enzymes and bile acids among ill children with severe acute malnutrition is safe and reduces the risk of death, deterioration or readmission to hospital.
Read the detailed description
Severely malnourished children who present with an acute illness have a high risk of mortality. Severe malnutrition is associated with intestinal inflammation and changes in the fecal microbiome ('dysbiosis'). Apart from in the large intestine, dysbiosis is also present in the small (upper) intestine, where increased bacterial density and altered microbial composition can contribute to intestinal inflammation and intestinal dysfunction which may ultimately contribute to the development of sepsis and death. The bacterial density and composition in the small intestine can be altered using antibiotics. However, apart from side effects, antibiotic use contributes to the development of antibiotic resistance, which is very common in hospitalized malnourished patients and can pose a threat to both individual and public health. In addition to intestinal dysbiosis and intestinal inflammation, children with severe malnutrition suffer from impaired exocrine pancreatic and hepatobiliary function, which are important for nutrient digestion and absorption to aid their recovery.
One previous pilot trial showed that treating children with severe malnutrition with pancreatic enzymes led to a reduction in mortality. The investigators hypothesize that supplementing these enzymes exogenously to severely malnourished children will improve their clinical outcome by reducing dysbiosis, intestinal inflammation and sepsis.
The objective of this study is to determine whether treating ill severely malnourished children with pancreatic enzymes or bile acids is safe and improves mortality. The investigators will conduct a double blind, randomized clinical trial in a 2x2 factorial design in hospitalized severely malnourished children. Participants will be treated with pediatric formulations of pancreatic enzymes, bile acids, both or placebo for 21 days. Participants will be followed up daily during their hospital stay and on day 21 and 60 after enrollment.
This trial will be conducted in three stages to allow for careful interim evaluations to assess safety and study progress. After the first and second stage, interim analyses assess safety and likelihood of benefit before enrolling the full sample size to assess mortality as the primary outcome. Secondary outcomes include adverse events, length of hospital stay and growth. Exploratory outcomes will examine intestinal and systemic inflammation and metabolic changes to examine mechanisms affected by the interventions, and costs.
Two sub-studies will be conducted. In Kenya and Bangladesh, daily blood gases, lactate and biochemistry for the first 5 days to assess early clinical progress. In Malawi and Uganda, hydrogen breath testing will be used to evaluate impact on upper small intestinal bacterial overgrowth.
Overall, this trial will determine whether a non-antibiotic, bactericidal intervention given in additional to standard of care management reduces mortality in acutely ill severely malnourished children.
- Conditions
- SEPSIS, MALNUTRITION, CHILD
- Being tested
- Pancreatic Enzyme, Ursodeoxycholic acid, Pancreatic Enzyme placebo, Ursodeoxycholic acid placebo
- Keywords
- "small intestinal bacterial overgrowth", "severe malnutrition", "factorial", "pancreatic enzymes", "bile acids", "bacterial", "translocation", "dysbiosis", "inflammation"
- Medical subject headings
- Sepsis, Child Nutrition Disorders, Malnutrition, Dysbiosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pancreatic EnzymeDrug
Also called CREON
CREON micro 5000
Ursodeoxycholic acidDrug
Also called UDCAMENT
Ursodiol C24H40O4 suspension
Pancreatic Enzyme placeboOther
Also called Placebo-PE
Microcrystalline Cellulose,Macrogel 4000, Iron Oxide Yellow, Iron Oxide Red, Activated Charcoal.
Ursodeoxycholic acid placeboOther
Also called Placebo-UA
Sodium Citrate Dihydrate, Aspartame, Carboxymethylcellulose Sodium, Citric Acid Monohydrate, Dispersible Cellulose, Glycerol, Polysorbate-80, Saccharin Sodium,Sodium Benzoate, Sodium Methylparaben, Sodium Propylparaben
| Study group | Role | What they receive |
|---|---|---|
| Pancreatic Enzymes (PE) | Active comparator | Pancreatic enzymes formulated as 5000 IE lipase, 3600 IE amylase and 200 IE protease per 100 mg of granules, packaged as sachets. The target dose is 3000 IU lipase/kg, twice daily (1440 IU/kg amylase/80 IU/kg protease), which is the dose used for children with cystic fibrosis and exocrine pancreas insufficiency. For oedematous malnutrition, weight for dosing is reduced by 10%. To be prescribed following enrolment and given just prior to or during a feed. Prescription will follow weight bands to allow a lower range of 2000 IU/kg/day and upper range of 4000 IU/kg/day:
Weight from Weight to Dose Dose Upper range Lower range (Kg) (Kg) (sachets) (IU Lipase) (IU/kg/dose) (IU Lipase)
---------------------------------------------------------------------------------------------------------- 2.50 4.99 2 10000 4000 2000 5.00 7.49 4 20000 4000 2670 7.50 9.99 6 30000 4000 3000 10.0 15.0 8 40000 4000 2667 Receives: Drug: Pancreatic Enzyme |
| Placebo-PE | Placebo comparator | Oral/enteral placebo matching active Pancreatic Enzymes (PE). Dose presentation in whole sachets of 100mg of granules. For oedematous malnutrition, weight for dosing is reduced by a pragmatic 10%. To be prescribed following enrolment and given just prior to or during a feed. Prescription will follow weight bands:
Weight from Weight to Dose Dose Upper range Lower range (Kg) (Kg) (sachets) (IU Lipase) (IU/kg/dose) (IU Lipase)
----------------------------------------------------------------------------------------------------------------------------------------- 2.50 4.99 2 Nil Nil Nil 5.00 7.49 4 Nil Nil Nil 7.50 9.99 6 Nil Nil Nil 10.0 15.0 8 Nil Nil Nil Receives: Other: Pancreatic Enzyme placebo |
| Ursodeoxycholic acid (UA) | Active comparator | The dose of ursodeoxycholic acid will be given at 10 mg/kg twice per day just prior to or during a feed, using a suspension of 50 mg/ml = 0.2 ml/kg. For oedematous malnutrition participants, weight is pragmatically reduced by 10%. To be prescribed and given following enrolment. Receives: Drug: Ursodeoxycholic acid |
| Placebo-UA | Placebo comparator | The dose of placebo will be given twice per day just prior to or during a feed at 0.2 ml/kg. To be prescribed and given following enrolment. Receives: Other: Ursodeoxycholic acid placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Death
Measured: 60 days
Secondary outcomes (9)
Rate of SAEs
All serious adverse events
Measured: 60 days
Rate of toxicity events
Grade 3 or 4 toxicity events whilst receiving investigational products
Measured: 21 days
Intestinal function
number of days with diarrhoea during index hospital admission
Measured: 60 days
Antimicrobials
Days on second and third-line antibiotics during index admission and readmission
Measured: 60 days
Hospitalisation duration
Number of days from enrolment to discharge during index admission
Measured: 60 days
Growth - arm circumference cm
Change in MUAC in cm between enrolment and 60 days later
Measured: 60 Days
Growth - weight for age z score
Change in weight for age z score between enrolment and 60 days later
Measured: 60 days
Growth - weight for length z score
Change in weight for length z score between enrolment and 60 days later
Measured: 60 days
Growth - length for age z score
Change in length for age z score between enrolment and 60 days later
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start1 Jul 2021
- Primary completion31 Oct 2023 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SEPSISStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Double-blind, randomized clinical trial 2x2 factorial design in 3 stages: In stage 1, (200 participants). Then the Data \& Safety Monitoring Committee (DSMC) will review data for likelihood major safety signals/harm (non-inferior to placebo) based on a composite endpoint of toxicity, serious adverse events (SAEs) and deaths. In stage 2, (200 more participants, total 400 participants). Then the DSMC will review data on a composite endpoint of SAEs and deaths and results of modeled simulations for the likelihood of superiority over placebo for mortality. Interventions with less than 80% probability of efficacy will be discontinued. Sample size for stage 3 may be adjusted. In stage 3, (800 more participants, total target sample size 1,200) across all sites, based on a hazard ratio of 0.66 (a 33% reduction in mortality) from a baseline mortality of 24% to 16% with 90% power, 20% inflation for the factorial design and 5% loss to follow up.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Amsterdam, University of Toronto, University of Washington, Oregon Health and Science University, Kenya Medical Research Institute, Queen Elizabeth Central Hospital, Blantyre, Malawi, Makerere University, KEMRI-Wellcome Trust Collaborative Research Program, International Centre for Diarrhoeal Disease Research, Bangladesh
- Responsible party
- Sponsor
- Investigators
- James A Berkley, MD, Study chair, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04542473
- Sponsor's protocol ID
- OxTREC 43-20
- Acronym
- PB-SAM
- Status last verified
- Feb 2023
- First submitted
- 6 Aug 2020
- Last updated
- 24 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymised data may be shared through application to DGC@kemri-wellcome.org. Datasets will be uploaded on the HARVARD DATAVERSE for managed access
Publications
Zhang L, Voskuijl W, Mouzaki M, Groen AK, Alexander J, Bourdon C, Wang A, Versloot CJ, Di Giovanni V, Wanders RJ, Bandsma R. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition. PLoS One. 2016 May 10;11(5):e0155143. doi: 10.1371/journal.pone.0155143. eCollection 2016.
PubMed 27163928Bartels RH, Bourdon C, Potani I, Mhango B, van den Brink DA, Mponda JS, Muller Kobold AC, Bandsma RH, Boele van Hensbroek M, Voskuijl WP. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial. J Pediatr. 2017 Nov;190:85-92.e2. doi: 10.1016/j.jpeds.2017.07.013. Epub 2017 Sep 11.
PubMed 28912050Njunge JM, Gwela A, Kibinge NK, Ngari M, Nyamako L, Nyatichi E, Thitiri J, Gonzales GB, Bandsma RHJ, Walson JL, Gitau EN, Berkley JA. Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition. Sci Rep. 2019 Apr 12;9(1):5981. doi: 10.1038/s41598-019-42436-y.
PubMed 30979939Attia S, Versloot CJ, Voskuijl W, van Vliet SJ, Di Giovanni V, Zhang L, Richardson S, Bourdon C, Netea MG, Berkley JA, van Rheenen PF, Bandsma RH. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study. Am J Clin Nutr. 2016 Nov;104(5):1441-1449. doi: 10.3945/ajcn.116.130518. Epub 2016 Sep 21.
PubMed 27655441Bandsma RHJ, Chisti MJ, Voskuijl WP, Ngari MM, Mupere E, Njagi I, Thitiri J, Potani I, Mbale E, Chasweka D, Makwinja C, Eneya C, Bourdon C, Mohammad Sayeem Bin Shahid AS, Shaima SN, Salahuddin Mamun GM, Lancioni CL, Maronga C, Lwanga C, Atuhairwe M, Tickell KD, Tigoi C, Mburu M, Ngao N, Dmitrienko A, Afroze F, Shahrin L, Ahmed T, Walson JL, Berkley JA. Pancreatic enzymes and bile acids alone and in combination for acutely ill, severely malnourished children: a multi-country double-blind randomised placebo-controlled trial. EClinicalMedicine. 2026 Aug 15;99:104110. doi: 10.1016/j.eclinm.2026.104110. eCollection 2026 Sep.
PubMed 42643234
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pancreatic Enzymes and Bile Acids: A Non-Antibiotic Approach to Treat Intestinal Dysbiosis in Acutely Ill Severely Malnourished Children
- ClinicalTrials.gov ID
- NCT04542473
- Acronym / sponsor ID
- PB-SAM / OxTREC 43-20
- Conditions
- SEPSIS, MALNUTRITION, CHILD
- Keywords
- "small intestinal bacterial overgrowth", "severe malnutrition", "factorial", "pancreatic enzymes", "bile acids", "bacterial", "translocation", "dysbiosis"
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Amsterdam, University of Toronto, University of Washington, Oregon Health and Science University, Kenya Medical Research Institute, Queen Elizabeth Central Hospital, Blantyre, Malawi, Makerere University, KEMRI-Wellcome Trust Collaborative Research Program, International Centre for Diarrhoeal Disease Research, Bangladesh
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 31 Oct 2023 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 9 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Children with severe malnutrition who are sick and admitted to hospitals have high mortality, usually because of infection. Malnourished children have more potentially harmful bacteria in their upper intestines than well-nourished children and this may contribute to inflammation in the gut and whole body. These bacteria may cross from the intestines to the bloodstream causing life-threatening infections. A related abnormality among malnourished children is reduction in the digestive enzymes made by the pancreas and the liver. Apart from helping with digestion of food, these enzymes are important in helping the body control bacteria in the upper intestines. It is therefore possible that treatment with digestive enzymes could help reduce the burden of harmful bacteria and thus lower inflammation and the risk of serious infection. One study conducted in Malawi has shown that children with severe malnutrition who were supplemented with pancreatic enzymes had a lower risk of dying. However, this was a small study and although promising, requires validation. No studies of supplementation with bile acids have been done among severely malnourished children. However, bile acids are commonly used to manage patients with liver function abnormalities, something that malnourished children suffer from as well. The investigators want to find out if supplementing these pancreatic enzymes and bile acids among ill children with severe acute malnutrition is safe and reduces the risk of death, deterioration or readmission to hospital.
Detailed description
Severely malnourished children who present with an acute illness have a high risk of mortality. Severe malnutrition is associated with intestinal inflammation and changes in the fecal microbiome ('dysbiosis'). Apart from in the large intestine, dysbiosis is also present in the small (upper) intestine, where increased bacterial density and altered microbial composition can contribute to intestinal inflammation and intestinal dysfunction which may ultimately contribute to the development of sepsis and death. The bacterial density and composition in the small intestine can be altered using antibiotics. However, apart from side effects, antibiotic use contributes to the development of antibiotic resistance, which is very common in hospitalized malnourished patients and can pose a threat to both individual and public health. In addition to intestinal dysbiosis and intestinal inflammation, children with severe malnutrition suffer from impaired exocrine pancreatic and hepatobiliary function, which are important for nutrient digestion and absorption to aid their recovery.
One previous pilot trial showed that treating children with severe malnutrition with pancreatic enzymes led to a reduction in mortality. The investigators hypothesize that supplementing these enzymes exogenously to severely malnourished children will improve their clinical outcome by reducing dysbiosis, intestinal inflammation and sepsis.
The objective of this study is to determine whether treating ill severely malnourished children with pancreatic enzymes or bile acids is safe and improves mortality. The investigators will conduct a double blind, randomized clinical trial in a 2x2 factorial design in hospitalized severely malnourished children. Participants will be treated with pediatric formulations of pancreatic enzymes, bile acids, both or placebo for 21 days. Participants will be followed up daily during their hospital stay and on day 21 and 60 after enrollment.
This trial will be conducted in three stages to allow for careful interim evaluations to assess safety and study progress. After the first and second stage, interim analyses assess safety and likelihood of benefit before enrolling the full sample size to assess mortality as the primary outcome. Secondary outcomes include adverse events, length of hospital stay and growth. Exploratory outcomes will examine intestinal and systemic inflammation and metabolic changes to examine mechanisms affected by the interventions, and costs.
Two sub-studies will be conducted. In Kenya and Bangladesh, daily blood gases, lactate and biochemistry for the first 5 days to assess early clinical progress. In Malawi and Uganda, hydrogen breath testing will be used to evaluate impact on upper small intestinal bacterial overgrowth.
Overall, this trial will determine whether a non-antibiotic, bactericidal intervention given in additional to standard of care management reduces mortality in acutely ill severely malnourished children.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Double-blind, randomized clinical trial 2x2 factorial design in 3 stages: In stage 1, (200 participants). Then the Data \& Safety Monitoring Committee (DSMC) will review data for likelihood major safety signals/harm (non-inferior to placebo) based on a composite endpoint of toxicity, serious adverse events (SAEs) and deaths. In stage 2, (200 more participants, total 400 participants). Then the DSMC will review data on a composite endpoint of SAEs and deaths and results of modeled simulations for the likelihood of superiority over placebo for mortality. Interventions with less than 80% probability of efficacy will be discontinued. Sample size for stage 3 may be adjusted. In stage 3, (800 more participants, total target sample size 1,200) across all sites, based on a hazard ratio of 0.66 (a 33% reduction in mortality) from a baseline mortality of 24% to 16% with 90% power, 20% inflation for the factorial design and 5% loss to follow up.
| Arm | Type | Receives |
|---|---|---|
| Pancreatic Enzymes (PE) | Active comparator | Drug: Pancreatic EnzymePancreatic enzymes formulated as 5000 IE lipase, 3600 IE amylase and 200 IE protease per 100 mg of granules, packaged as sachets. The target dose is 3000 IU lipase/kg, twice daily (1440 IU/kg amylase/80 IU/kg protease), which is the dose used for children with cystic fibrosis and exocrine pancreas insufficiency. For oedematous malnutrition, weight for dosing is reduced by 10%. To be prescribed following enrolment and given just prior to or during a feed. Prescription will follow weight bands to allow a lower range of 2000 IU/kg/day and upper range of 4000 IU/kg/day: Weight from Weight to Dose Dose Upper range Lower range (Kg) (Kg) (sachets) (IU Lipase) (IU/kg/dose) (IU Lipase) ---------------------------------------------------------------------------------------------------------- 2.50 4.99 2 10000 4000 2000 5.00 7.49 4 20000 4000 2670 7.50 9.99 6 30000 4000 3000 10.0 15.0 8 40000 4000 2667 |
| Placebo-PE | Placebo comparator | Other: Pancreatic Enzyme placeboOral/enteral placebo matching active Pancreatic Enzymes (PE). Dose presentation in whole sachets of 100mg of granules. For oedematous malnutrition, weight for dosing is reduced by a pragmatic 10%. To be prescribed following enrolment and given just prior to or during a feed. Prescription will follow weight bands: Weight from Weight to Dose Dose Upper range Lower range (Kg) (Kg) (sachets) (IU Lipase) (IU/kg/dose) (IU Lipase) ----------------------------------------------------------------------------------------------------------------------------------------- 2.50 4.99 2 Nil Nil Nil 5.00 7.49 4 Nil Nil Nil 7.50 9.99 6 Nil Nil Nil 10.0 15.0 8 Nil Nil Nil |
| Ursodeoxycholic acid (UA) | Active comparator | Drug: Ursodeoxycholic acidThe dose of ursodeoxycholic acid will be given at 10 mg/kg twice per day just prior to or during a feed, using a suspension of 50 mg/ml = 0.2 ml/kg. For oedematous malnutrition participants, weight is pragmatically reduced by 10%. To be prescribed and given following enrolment. |
| Placebo-UA | Placebo comparator | Other: Ursodeoxycholic acid placeboThe dose of placebo will be given twice per day just prior to or during a feed at 0.2 ml/kg. To be prescribed and given following enrolment. |
Who may qualify
- Ages
- 2 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Age 2 to <59 months
- Admitted to hospital with an acute, non-traumatic illness and within 72 hours of admission at the time of enrolment
- Severe malnutrition (weight-for-height <-3 z scores of the median WHO growth standards and/or mid upper arm circumference <115mm (<110mm age below 6 months), or symmetrical oedema of at least the feet related to malnutrition (not related to a primary cardiac or renal disorder)
- Able to feed orally in usual state of health.
- Accompanied by care provider who provides written informed consent
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pancreatic EnzymeAlso: CREONCREON micro 5000 | Drug | Pancreatic Enzymes (PE) |
| Ursodeoxycholic acidAlso: UDCAMENTUrsodiol C24H40O4 suspension | Drug | Ursodeoxycholic acid (UA) |
| Pancreatic Enzyme placeboAlso: Placebo-PEMicrocrystalline Cellulose,Macrogel 4000, Iron Oxide Yellow, Iron Oxide Red, Activated Charcoal. | Other | Placebo-PE |
| Ursodeoxycholic acid placeboAlso: Placebo-UASodium Citrate Dihydrate, Aspartame, Carboxymethylcellulose Sodium, Citric Acid Monohydrate, Dispersible Cellulose, Glycerol, Polysorbate-80, Saccharin Sodium,Sodium Benzoate, Sodium Methylparaben, Sodium Propylparaben | Other | Placebo-UA |
Primary outcome
Mortality
Time frame: 60 days
Death
9 secondary outcomes
Rate of SAEs
Time frame: 60 days
Rate of toxicity events
Time frame: 21 days
Intestinal function
Time frame: 60 days
Antimicrobials
Time frame: 60 days
Hospitalisation duration
Time frame: 60 days
Growth - arm circumference cm
Time frame: 60 Days
Growth - weight for age z score
Time frame: 60 days
Growth - weight for length z score
Time frame: 60 days
Growth - length for age z score
Time frame: 60 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2023.
- Background: PubMed 27163928Zhang L, Voskuijl W, Mouzaki M, Groen AK, Alexander J, Bourdon C, Wang A, Versloot CJ, Di Giovanni V, Wanders RJ, Bandsma R. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition. PLoS One. 2016 May 10;11(5):e0155143. doi: 10.1371/journal.pone.0155143. eCollection 2016.
- Background: PubMed 28912050Bartels RH, Bourdon C, Potani I, Mhango B, van den Brink DA, Mponda JS, Muller Kobold AC, Bandsma RH, Boele van Hensbroek M, Voskuijl WP. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial. J Pediatr. 2017 Nov;190:85-92.e2. doi: 10.1016/j.jpeds.2017.07.013. Epub 2017 Sep 11.
- Background: PubMed 30979939Njunge JM, Gwela A, Kibinge NK, Ngari M, Nyamako L, Nyatichi E, Thitiri J, Gonzales GB, Bandsma RHJ, Walson JL, Gitau EN, Berkley JA. Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition. Sci Rep. 2019 Apr 12;9(1):5981. doi: 10.1038/s41598-019-42436-y.
- Background: PubMed 27655441Attia S, Versloot CJ, Voskuijl W, van Vliet SJ, Di Giovanni V, Zhang L, Richardson S, Bourdon C, Netea MG, Berkley JA, van Rheenen PF, Bandsma RH. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study. Am J Clin Nutr. 2016 Nov;104(5):1441-1449. doi: 10.3945/ajcn.116.130518. Epub 2016 Sep 21.
- Derived from this study: PubMed 42643234Bandsma RHJ, Chisti MJ, Voskuijl WP, Ngari MM, Mupere E, Njagi I, Thitiri J, Potani I, Mbale E, Chasweka D, Makwinja C, Eneya C, Bourdon C, Mohammad Sayeem Bin Shahid AS, Shaima SN, Salahuddin Mamun GM, Lancioni CL, Maronga C, Lwanga C, Atuhairwe M, Tickell KD, Tigoi C, Mburu M, Ngao N, Dmitrienko A, Afroze F, Shahrin L, Ahmed T, Walson JL, Berkley JA. Pancreatic enzymes and bile acids alone and in combination for acutely ill, severely malnourished children: a multi-country double-blind randomised placebo-controlled trial. EClinicalMedicine. 2026 Aug 15;99:104110. doi: 10.1016/j.eclinm.2026.104110. eCollection 2026 Sep.
- The CHAIN NetworkLink provided by the sponsor.
- Individual participant dataSharing planned: No. Anonymised data may be shared through application to DGC@kemri-wellcome.org. Datasets will be uploaded on the HARVARD DATAVERSE for managed access
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Integrated Medicine for Sepsis: An RCT With Phenotyping
Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James A Berkley, MD study chair
University of Oxford
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pancreatic Enzyme and Ursodeoxycholic acid in people with SEPSIS and MALNUTRITION, CHILD, run by University of Oxford at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Bangladesh, Kenya, Malawi, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04542473, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2023.