Bwakura-Dangarembizi Mutsa, Amadi Beatrice, Singa Benson O, Muyemayema Sofia, Ngosa Deophine, Mwalekwa Laura, Ngao Narshion, Kazhila Lydia, Mutasa Batsirai, Mpofu Eddington, Mudawarima Louisa, Gonzales Gerard Bryan, Mudzingwa Shepherd, Mutenda Mukumbi, Keter Lucia K, Mutasa Kuda, Njunge James M, Jones Helen, Phiri Tracy Naomi, Mudibo Evans, Chulu Nivea, Majo Florence D, Chasekwa Bernard, Tembo Aaron, Nyabinda Churchil, Oduol Chris, Sauramba Virginia, Tavengwa Naume V, Langhaug Lisa, Cordani Isabella, Smuk Melanie, Jaki Thomas, Ntozini Robert, Walson Judd, Tickell Kirkby D, Berkley James, Kelly Paul, Prendergast Andrew J
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
University of Zimbabwe, Harare, Zimbabwe.
BMJ Open. 2025 May 24;15(5):e093758. doi: 10.1136/bmjopen-2024-093758.
Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, readmission and failed nutritional recovery. Current management approaches fail to sufficiently promote convalescence after inpatient nutritional rehabilitation. Novel interventions during the post-discharge period could enhance convalescence to help children survive and thrive.
The Co-SAM trial is an adaptive, multicountry, phase III, individually randomised clinical trial, based on the principles that (i) interacting biological and social factors drive multimorbidity in children with SAM, and (ii) both medical and psychosocial interventions may therefore ameliorate underlying causal pathways to reduce morbidity and mortality and improve recovery. Children aged 6-59 months with complicated SAM, who have stabilised and started the transition to ready-to-use therapeutic food (RUTF), will be enrolled and randomised to one of five trial arms (standard-of-care alone; antimicrobials; reformulated RUTF; psychosocial support; or a combination of all strategies). Standard-of-care, which is provided in all trial arms, includes RUTF until nutritional recovery (defined as weight-for-height Z-score >-2, mid-upper arm circumference >12.5 cm and oedema-free since the last study visit), and other management recommended in WHO guidelines. The 12-week antimicrobial package provides daily co-formulated rifampicin and isoniazid (with pyridoxine) and 3 days of azithromycin monthly. The reformulated RUTF, which incorporates medium-chain triglycerides and hydrolysed protein to increase nutrient bioavailability and reduce metabolic stress, is provided at the same dose and duration as standard RUTF. The 12-week psychosocial package includes caregiver problem-solving therapy, educational modules, peer support groups and child play. The combined arm includes all interventions. Children start their intervention package prior to hospital discharge, with follow-up data collection in study clinics at 2, 4, 6, 8, 12 and 24 weeks. The primary composite outcome is death, hospitalisation or failed nutritional recovery within 24 weeks post-randomisation. An interim analysis will allow unpromising arms to be dropped, while the final analysis will be conducted when 1266 children have completed the study. Embedded process evaluation and laboratory substudies will explore the mechanisms of action of the interventions.
The trial has been approved by ethics committees in Zimbabwe, Zambia, Kenya and UK. Dissemination will be via community advisory boards in each country; Ministries of Health; and dialogue with policymakers including UNICEF.
Clinicaltrials.gov: NCT05994742; Pan African Clinical Trials Registry: PACTR202311478928378.
患有复杂重度急性营养不良（SAM）的儿童出院后，面临着高死亡率、再次入院和营养恢复失败的风险。目前的管理方法未能充分促进住院营养康复后的康复。出院后期间的新型干预措施可以增强康复效果，帮助儿童生存和茁壮成长。
Co-SAM试验是一项适应性、多国、III期、个体随机临床试验，基于以下原则：（i）相互作用的生物和社会因素导致SAM儿童出现多种疾病，（ii）因此，医学和心理社会干预措施都可能改善潜在的因果途径，以降低发病率和死亡率，并改善康复情况。年龄在6至59个月、患有复杂SAM且病情已稳定并开始过渡到即用型治疗食品（RUTF）的儿童将被纳入研究，并随机分配到五个试验组之一（仅标准治疗；抗菌药物；重新配方的RUTF；心理社会支持；或所有策略的组合）。所有试验组均提供标准治疗，包括提供RUTF直至营养恢复（定义为身高别体重Z评分>-2、上臂中部周长>12.5厘米且自上次研究访视后无水肿），以及世界卫生组织指南中推荐的其他管理措施。为期12周的抗菌药物套餐包括每日联合使用的利福平、异烟肼（加维生素B6）以及每月3天的阿奇霉素。重新配方的RUTF含有中链甘油三酯和水解蛋白，以提高营养生物利用度并减轻代谢压力，其剂量和使用时间与标准RUTF相同。为期12周的心理社会套餐包括照顾者问题解决疗法、教育模块、同伴支持小组和儿童游戏。联合组包括所有干预措施。儿童在出院前开始其干预套餐，并在研究诊所于第2、4、6、8、12和24周收集随访数据。主要复合结局是随机分组后24周内的死亡、住院或营养恢复失败。中期分析将允许放弃无前景的组，而最终分析将在1266名儿童完成研究时进行。嵌入式过程评估和实验室子研究将探索干预措施的作用机制。
该试验已获得津巴布韦、赞比亚、肯尼亚和英国伦理委员会的批准。传播将通过每个国家的社区咨询委员会、卫生部以及与包括联合国儿童基金会在内的政策制定者进行对话来进行。
Clinicaltrials.gov：NCT05994742；泛非临床试验注册中心：PACTR202311478928378。
