An interventional study of F75 milk feeds and F60 milk feeds in Dietary Supplementation, Severe Acute Malnutrition and Children, sponsored by International Centre for Diarrhoeal Disease Research, Bangladesh. Enrolling by invitation at 1 site in Bangladesh. Open to participants aged 6 Months to 59 Months. Per ClinicalTrials.gov, last updated 2026-08-07.
Sponsored by International Centre for Diarrhoeal Disease Research, Bangladesh · Not applicable, Interventional, and Treatment
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.
Outcomes for children with SAM have improved over the past 20 years. Community-based treatment programs and RUTF are making an impact. However, outcomes lag for hospitalized children with SAM. In many settings, more than 10% of these children die. Inpatient outcomes for children with SAM may be improved by more precisely matching the nutritional composition of the formula that is provided during stabilization to the unique nutritional requirements of children hospitalized with SAM. Specifically, modifying the nutrient profile of stabilization formula may reduce mortality, by reducing risk for complications such as refeeding syndrome, while supporting earlier recovery.
Therapeutic formulas for treating SAM were developed gradually, over the course of several decades. A basic goal of stabilizing care is to limit subsequent risk for refeeding syndrome, which occurs most often when the extra energy and protein needed for catch-up growth are introduced. The current standard of care stabilization formula, F-75, was developed to replenish electrolytes and to correct metabolic abnormalities. F-75 was formalized by WHO in 1999. Since then, widening access to community-based treatment programs for SAM has altered patient volume and acuity on malnutrition wards. Fewer children are now hospitalized for SAM. However, the total global requirement for for F-75 continues to grow, with stockouts now increasingly frequent.This may be partly due to increased acuity and length of stay among children with SAM who need hospitalization. An improved stabilization formula has the potential to improve outcomes for these medically fragile children, while also reducing costs by shortening the average length of stay.
F-60 is a novel therapeutic formula intended, like F-75, for children with SAM who need inpatient stabilization. Data on the energy requirements and optimal nutrient composition of therapeutic feeds have remained limited since their original development in the 1980s-1990s. The nutritional profile of F-60 reflects recent clinical evidence and regulatory guidance ensuring consistency with the most current scientific and regulatory recommendations. F-60 contains less energy (60 kcal/100ml) than F-75 (77 kcal/100ml). F-60 also contains greater concentrations of particular vitamins, minerals, methyl donors, and amino acids. From a regulatory standpoint, F-60 is a 'formula for special medical purposes'. It has not yet been tested in children. In this respect, F-60 is an investigational product. Much has been learned about malnutrition since F-75 was conceptualized more than 40 years ago. In developed settings, strategies to prevent refeeding syndrome are now increasingly nuanced. The design of F-60 reflects these recent insights, including one-carbon dysfunction, intestinal barrier dysfunction, metabolic recovery and risk of refeeding syndrome.
The trial proposed here aims to assess the biochemical and clinical safety of F-60, relative to the current standard of care, F-75.
The nutrient profile of F-60 has been meticulously formulated for this trial. F-60 contains less energy than F-75, which provides 77 kcal/100 ml, exceeding the Codex maximum of 70 kcal/100 ml. (8) Total energy content of F-60 reflects the Codex minimum (60 kcal/100 ml). This change aims to match the measured median resting energy expenditure in most children with SAM (≈78 kcal/kg/day). The reduction of energy in F-60 is achieved mainly by reducing the carbohydrate content. F-60 is fortified with essential amino acids. F-60 contains more milk protein and five essential amino acids that are particularly limiting in the diets that are associated with SAM: lysine, methionine, cysteine, threonine, and tryptophan. F-60 contains greater concentrations of certain electrolytes relative to F-75. These changes are intended to reduce the risk of cardiac conduction disturbances by more quickly repleting diminished electrolyte stores, a frequent occurrence in SAM. Potassium deficiency is common in SAM. Potassium is increased in F-60. F-75 contains 145 mg of potassium per 100 ml. F-60 provides 200 mg per 100 ml. The total phosphorus content of F-60 is comparable, providing \~ 117 mg/kg/day. The increased phosphorous content of F-75 is designed to more effectively replenish phosphorus stores. Magnesium depletion increases risk for cardiac arrhythmias during refeeding. F-60 provides more magnesium (23.4 mg/kg/day) than F-75 (12.3 mg/kg/day), when children are treated with a standard feed volume (ie, 130 ml/kg/day). F-60 incorporates modest trace mineral adjustments. These changes aim to ensure comparable intake between children consuming F-75 and F-60. Some moderate increases in F-60 reflect the greater inclusion of milk powder in F-60, which contains multiple trace minerals. F-60 provides increased amounts of water-soluble vitamins; B vitamins and vitamin C. These changes aim to support quicker metabolic recovery during stabilization. Thiamine (B1) is increased in F-60. Acute thiamine deficiency causes severe morbidity. Riboflavin (B2) is increased in F-60. Riboflavin supports energy metabolism and plays a vital role in one-carbon movement by supporting folate regeneration. Vitamin B3 (nicotinamide) is increased in F-60. B3 content in F-60 is increased to levels shown to support immune function. Pantothenic Acid (B5) is increased in F-60. Pantothenic acid is required for the synthesis of coenzyme A and acyl carrier protein. Both are essential for lipid metabolism. Pyridoxine (B6) is increased in F-60, providing \~0.32 mg/kg/day. Biotin (B7) is increased in F-60. Biotin is a coenzyme for carboxylases involved in fatty acid metabolism and keratin synthesis. Folate (B9) is increased in F-60. Folate is essential for one-carbon metabolism. It supports the transfer of methyl groups in the folate cycle. Cobalamin (B12) is increased in F-60: It supports two key enzymes: methylmalonyl-CoA mutase and methionine synthase, both essential for energy metabolism and one-carbon flux. Vitamin C is increased in F-60. Children who develop SAM often consume diets largely devoid of fresh fruits and vegetables, containing limited amounts of vitamin C. F-75 contains fat-soluble vitamins at levels adequate for age-specific nutritional requirements. F-60 preserves this standard for vitamins A, D, and E, with adjustments limited to ensuring intake that is comparable with F-75. In contrast, vitamin K content is increased in F-60. Carnitine, inositol, and taurine supplemented in F60 according to to current Codex Alimentarius guidelines. Choline is increased in F-60. The additional choline in F-60 aims to support cell membrane renewal, one-carbon function, and efficient energy metabolism during stabilization of SAM.
82 studies on the registry are indexed under Severe Acute Malnutrition; 13 are open to participants now.
This study's planned enrollment of 320 is below the median of 400 across 69 interventional studies indexed under Severe Acute Malnutrition.
Browse Severe Acute Malnutrition studies →International Centre for Diarrhoeal Disease Research, Bangladesh is the lead sponsor of 206 studies on the registry; 31 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Standard 'F75' (77 kcal/100 ml) provides 95 kcal/kg/day
F-60 contains 60 kcal/100ml, and provides 78 kcal/kg/day
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.
Time frame: 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".
Death during hospitalization
The study will compare all-cause inpatient mortality between the intervention (F-60) and control (F-75) arms.
Time frame: 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
Laboratory indices (e.g., serum sodium, potassium, glucose, phosphate, magnesium, albumin) are measured at baseline, again at 48 hours, and every 48 hours thereafter while children remain hospitalized and are receiving either the control (F-75) or intervention (F-60) product. Defining fixed measurement time points and a standardized set of laboratory parameters permits comparison of the intervention and control products at consistent points in time across a heterogeneous population of children and hospitalization courses.
Time frame: 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)
Children with SAM who are unable to transition from their initial stabilization formula to ready-to-use therapeutic food often experience worsened outcomes. For this reason, time to complete the transition from stabilization formula to ready-to-use therapeutic food is identified as a clinically relevant secondary outcome. The total number of days needed to complete stabilization and transition to ready-to-use therapeutic food will be compared between the intervention and control arms. The average time frame to complete stabilization is expected to be four to five days; the maximum duration is expected to be seven days. A child who fails to complete transition to ready-to-use therapeutic food within seven days will be assigned an outcome of "delayed transition."
Time frame: 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 number of loose stools a child experiences each day during hospitalization will be recorded. Diarrhea is defined as three or more loose stools within a 24-hour period.
Time frame: 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
Any child whose condition deteriorates to the extent that they require an escalation of care, requiring their transfer from a general pediatrics ward to an ICU setting, will be recorded as having met "escalation of care to ICU." The expected time frame includes the entire duration of hospitalization, the average of which is expected to be five to seven days, with nearly all children completing hospitalization within 21 days. Escalation of a child's care to an ICU setting will constitute a secondary outcome even when the child is no longer receiving one of the stabilization products.
Time frame: The expected time frame of observation will be "from randomization to discharge, which is, on average, 7 days".
Hypoglycaemia during stabilization
Blood glucose less than 3 mmol/l by finger prick
Time frame: From randomization until initiation of transition to ready to use therapeutic food, with an expected average observation time frame of 3 to 5 days.
Increase in PEWS score and low blood pressure
Pediatric early warning score (PEWS) and blood pressure will be assessed twice daily
Time frame: From randomization to discharge, which is on average 7 days.
Hospital-acquired infection
Investigators will follow the patient twice daily during hospitalization, and Investigators will follow the standardized Hospital-acquired infection (HAI) definition to identify any new-onset infections after randomization and 3 days after discharge from the hospital.HAIs are infections that occur while receiving health care, are developed in a hospital or other health care facility, and that first appear 48 hours or more after hospital admission.
Time frame: From "randomization to discharge, and any readmission within 3 days after discharge".
Need for electrolyte replacement
replacement of potassium, calcium, and magnesium
Time frame: From randomization to 48 hours after enrollment
Plan to share: No — Only SAE's will be shared with DSMB as individual participant data
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