Safety Trial of F-60 Among Children Hospitalized With SAM

NCT07752628 | Enrolling By Invitation DMC

• 1 other identifier: PR- 25-014
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

The current WHO-recommended F-75 diet for stabilization of SAM has remained largely unchanged since its development in the 1990s. No clinical trial has studied enhanced therapeutic formulas during the stabilization phase, particularly in high-burden, low-resource settings. Additionally, the current F75 nutritional formula was based only on expert opinion, not scientific evidence. Evidence suggests that modifying the nutrient profile of stabilization formulas may improve survival, reduce complications such as refeeding syndrome, and enhance early recovery. A better stabilization formula for these medically fragile children has the potential to reduce mortality. The purpose of this randomized controlled clinical trial (RCT) is to test the hypothesis that an enhanced nutrient fortified therapeutic stabilization formula (F-60) will improve outcomes for children hospitalized with SAM, relative to the current standard of care (F-75). Hypothesis: The main hypothesis of this safety study is that F-60 is not inferior to F-75. Objectives: To test this hypothesis, Investigators will pursue two specific aims. Aim 1: to assess laboratory outcomes in children stabilized with F-60. Aim 2: to assess clinical outcomes in children who receive F-60.

Conditions

Dietary Supplementation; Severe Acute Malnutrition; Children

Keywords

enhanced therapeutic formula; stabilization phase; clinical trial; Under five children; malnutrition; Bangladesh

Outcome Measures

Primary Outcomes (1)

• Comparing clinical and biochemical safety of F60 and F75

  This trial will compare the safety of F-60 with F-75. The primary endpoint is a prespecified hierarchical composite outcome, comprised of biochemical and clinical parameters and a win-ratio. For this study, the term "biochemical" includes all laboratory indices. Examples of biochemical indices that will be collected in this study include blood glucose, phosphate, magnesium, liver function tests, serum pH, serum lactate, and CRP/procalcitonin. Clinical parameters include death, delayed transition to RUTF, a need for ICU care, clinical deterioration as evident by an increase in PEWS score, blood pressure, need for electrolyte replacement, and time until diarrhea resolution. Participants will be compared individually, according to each relevant parameter, in a predefined sequence. The methods of Finkelstein and Schoenfeld will be used to calculate a win-ratio. This hierarchical composite will serve as the primary outcome for assessing the safety of F-60 relative to F-75.

  Primary outcome is a clinical composite consisting of clinical and laboratory-based parameters. Multiple outcomes included in this composite score will be recorded "from the time of randomization up until completion of hospitalization or up to 14 days".

Secondary Outcomes (9)

• Death during hospitalization

  The period of observation will extend from randomization until the time of discharge from the hospital. The average time frame will reflect "the average duration of hospitalization, 5-6 days, with most hospitalizations completed within 14 days".

• Abnormal laboratory indices at 48 hours

  Measured laboratory parameters will be assessed at 48 hours after randomization and then every 48 hours until scheduled lab draws cease, up to a maximum of 144 hours after randomization (e.g. < 7 days).

• Time to Complete Transition to Ready-to-Use Therapeutic Food (RUTF)

  The average time frame to complete stabilization is expected to be 4 to 5 days. The maximum duration is 7 days, beyond which point a child who fails to complete transition to RUTF will be assigned an outcome of "delayed transition."

• Time to resolve diarrhoea after enrollment

  The time until resolution of loose stools is expected to be less than 7 days (4 to 5 on average). Children whose diarrhea does not resolve before 7 days will be recorded as having prolonged diarrhea

• Escalation of care to the ICU

  The expected time frame of observation will be "from randomization to discharge, which is, on average, 7 days".

Study Arms (2)

F75 milk feeds

ACTIVE COMPARATOR

The WHO endorsed a standardized formulation of F-75 in the 1990s and energy density is 77 kcal/100ml. F75 aims to provide 95 kcal/kg/day and was intended to support children through early stabilization when fighting infections and is not aimed at weight gain.

Dietary Supplement: F75 milk feeds

F60 milk feeds

EXPERIMENTAL

F-60 contains an energy density of 60 kcal/100ml. F-60 also contains greater concentrations of particular vitamins, minerals, methyl donors, and amino acids.

Dietary Supplement: F60 milk feeds

Interventions

F75 milk feeds DIETARY_SUPPLEMENT

Standard 'F75' (77 kcal/100 ml) provides 95 kcal/kg/day

F75 milk feeds

F60 milk feeds DIETARY_SUPPLEMENT

F-60 contains 60 kcal/100ml, and provides 78 kcal/kg/day

F60 milk feeds

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 to 59 months.
• Severe Acute Malnutrition (WHZ \<-3 z-scores of the median WHO growth standards and/or MUAC \<11.5 cm or bilateral pitting nutritional edema).
• Received a maximum of 2 feeds of F75 (or milk suzi) at the time of enrolment.
• Primary caregiver is able to provide written or witnessed informed consent.

You may not qualify if:

• Congenital heart disease
• A known or suspected diagnosis of tuberculosis at the time of screening
• Anatomic abnormalities of the gastrointestinal tract
• Cancer
• Spastic cerebral palsy, hydrocephalus,
• Haemoglobinopathies.
• Children weigh more than 16 kg
• Diarrhea lasting more than 14 days prior to hospitalization.
• Children who require invasive critical care (ie, mechanical ventilation, continuous positive airway pressure (CPAP) \>5 cm H2O, or \>1 inotrope for BP support) will be ineligible. Informed written consent will be obtained from the child's guardian, following local practices.

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead

Study Sites (1)

Icddr,B

Dhaka, 1212, Bangladesh

Location

Related Publications (10)

• Tickell KD, Mangale DI, Tornberg-Belanger SN, Bourdon C, Thitiri J, Timbwa M, Njirammadzi J, Voskuijl W, Chisti MJ, Ahmed T, Shahid ASMSB, Diallo AH, Ouedrago I, Khan AF, Saleem AF, Arif F, Kazi Z, Mupere E, Mukisa J, Sukhtankar P, Berkley JA, Walson JL, Denno DM; Childhood Acute Illness and Nutrition Network. A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines. PLoS One. 2019 Mar 25;14(3):e0212395. doi: 10.1371/journal.pone.0212395. eCollection 2019.

  PMID: 30908499 BACKGROUND

• Bandsma RHJ, Voskuijl W, Chimwezi E, Fegan G, Briend A, Thitiri J, Ngari M, Mwalekwa L, Bandika V, Ali R, Hamid F, Owor B, Mturi N, Potani I, Allubha B, Muller Kobold AC, Bartels RH, Versloot CJ, Feenstra M, van den Brink DA, van Rheenen PF, Kerac M, Bourdon C, Berkley JA. A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial. PLoS Med. 2019 Feb 26;16(2):e1002747. doi: 10.1371/journal.pmed.1002747. eCollection 2019 Feb.

  PMID: 30807589 BACKGROUND

• Afroze F, Khoshnevisan F, Harawa PP, Islam Z, Bourdon C, Khoswe S, Islam M, Sarker SA, Islam F, Sayeem Bin Shahid ASM, Joosten K, Hulst JM, Eneya C, Walson JL, Berkley JA, Potani I, Voskuijl W, Ahmed T, Chisti MJ, Bandsma RHJ. Trajectories of resting energy expenditure and performance of predictive equations in children hospitalized with an acute illness and malnutrition: a longitudinal study. Sci Rep. 2024 Feb 13;14(1):3613. doi: 10.1038/s41598-024-53791-w.

  PMID: 38351162 BACKGROUND

• Childhood Acute Illness and Nutrition (CHAIN) Network. Characterising paediatric mortality during and after acute illness in Sub-Saharan Africa and South Asia: a secondary analysis of the CHAIN cohort using a machine learning approach. EClinicalMedicine. 2023 Feb 6;57:101838. doi: 10.1016/j.eclinm.2023.101838. eCollection 2023 Mar.

  PMID: 36825237 BACKGROUND

• Cussotto S, Delgado I, Anesi A, Dexpert S, Aubert A, Beau C, Forestier D, Ledaguenel P, Magne E, Mattivi F, Capuron L. Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation. Front Immunol. 2020 Apr 15;11:557. doi: 10.3389/fimmu.2020.00557. eCollection 2020.

  PMID: 32351500 BACKGROUND

• Talbert A, Thuo N, Karisa J, Chesaro C, Ohuma E, Ignas J, Berkley JA, Toromo C, Atkinson S, Maitland K. Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome. PLoS One. 2012;7(6):e38321. doi: 10.1371/journal.pone.0038321. Epub 2012 Jun 4.

  PMID: 22675542 BACKGROUND

• Sturgeon JP, Mufukari W, Tome J, Dumbura C, Majo FD, Ngosa D, Chandwe K, Kapoma C, Mutasa K, Nathoo KJ, Bourke CD, Ntozini R, Bwakura-Dangarembizi M, Amadi B, Kelly P, Prendergast AJ; HOPE-SAM study team. Risk factors for inpatient mortality among children with severe acute malnutrition in Zimbabwe and Zambia. Eur J Clin Nutr. 2023 Sep;77(9):895-904. doi: 10.1038/s41430-023-01320-9. Epub 2023 Aug 8.

  PMID: 37553508 BACKGROUND

• Vresk L, Flanagan M, Daniel AI, Potani I, Bourdon C, Spiegel-Feld C, Thind MK, Farooqui A, Ling C, Miraglia E, Hu G, Wen B, Zlotkin S, James P, McGrath M, Bandsma RHJ. Micronutrient status in children aged 6-59 months with severe wasting and/or nutritional edema: implications for nutritional rehabilitation formulations. Nutr Rev. 2025 Jan 1;83(1):112-145. doi: 10.1093/nutrit/nuad165.

  PMID: 38350491 BACKGROUND

• Baldeon ME, Zertuche F, Flores N, Fornasini M. Free Amino Acid Content in Human Milk is Associated with Infant Gender and Weight Gain during the First Four Months of Lactation. Nutrients. 2019 Sep 17;11(9):2239. doi: 10.3390/nu11092239.

  PMID: 31533347 BACKGROUND

• Langendorf C, Roederer T, de Pee S, Brown D, Doyon S, Mamaty AA, Toure LW, Manzo ML, Grais RF. Preventing acute malnutrition among young children in crises: a prospective intervention study in Niger. PLoS Med. 2014 Sep 2;11(9):e1001714. doi: 10.1371/journal.pmed.1001714. eCollection 2014 Sep.

  PMID: 25180584 BACKGROUND

MeSH Terms

Conditions

Severe Acute Malnutrition; Malnutrition

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2026
• First Posted: August 7, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 7, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)