Clinical Research Directory

Effectiveness of Simulation-based Training Delivered to Special Newborn Care Providers on Resuscitation Management and Kangaroo Mother Care: Simulation-based Training for Asyphxia in Babies Trial (STAR-Baby Trial)

Summary Background Neonatal mortality remains a major global public health challenge, with about 2.4 million newborn deaths occurring within the first month of life in 2020. Central and Southern Asia account for 36% of these deaths, with a neonatal mortality rate (NMR) of 23 per 1,000 live births. Birth asphyxia is a leading cause, responsible for nearly 900,000 deaths annually. In Nepal, neonatal mortality has remained stagnant over the past decade, with an NMR of 21 per 1,000 live births in both 2016 and 2022. This is far above the national Sustainable Development Goal target of 12 per 1,000 by 2030. Despite initiatives such as the Every Newborn Action Plan, more than 80% of neonatal deaths are still due to preventable causes such as prematurity, birth asphyxia, and infections. Although Nepal has expanded services through 61 Special Newborn Care Units (SNCUs), improvements in neonatal outcomes have been limited due to persistent gaps in quality of care and health worker skills. Studies highlight shortages of essential equipment, including neonatal resuscitation devices, and inadequate competency among providers, especially in managing non-breathing newborns. Provincial disparities further worsen outcomes and Lumbini provinces showing the highest NMRs. Poor facility readiness, lack of training, and limited availability of drugs and equipment contribute to suboptimal care. Hypothermia and inadequate Kangaroo Mother Care (KMC) practices also increase risks, particularly among low-birth-weight infants. Simulation-based training has emerged as an effective strategy to strengthen healthcare providers' skills in neonatal resuscitation. Evidence from countries like Tanzania shows improved clinical performance and reduced neonatal complications. The NeoNatalie™ simulator, a low-cost and portable training tool, has been effective in enhancing providers' competence and confidence. In Nepal's context of limited resources and skill gaps, such training offers a practical and scalable solution to improve neonatal outcomes and accelerate progress toward SDG targets. This study aims to evaluate the effectiveness of simulation-based training in improving the knowledge, skills, and performance of newborn care providers and reducing neonatal mortality in Nepal. Methods The study is designed as a two-arm, parallel cluster randomized controlled trial conducted in SNCUs across Lumbini province of Nepal. Hospitals will serve as clusters, with equal allocation into intervention and control groups. Participants will include medical officers, nurses, and paramedics working in SNCUs for at least six months. A total of 240 providers (120 per arm) will be enrolled, accounting for clustering and potential attrition. Randomization will be conducted by an independent statistician, with allocation concealment ensured. Intervention The intervention includes a three-day simulation-based training using the Helping Babies Breathe (HBB) program and NeoNatalie™ simulator. It covers essential newborn care, neonatal resuscitation within the "Golden Minute," breastfeeding, hypothermia prevention, KMC, and infection management. This will be followed by twelve months of mentoring and coaching by trained health workers. The control group will continue routine care. Data collection and analysis Data will be collected using standardized tools and electronic systems, ensuring quality monitoring. Data analysis will use appropriate statistical methods, including Analysis of Covariance (ANCOVA), to compare outcomes between groups. Ethical approval will be obtained from Nepal Health Research Council, and informed consent will be ensured. Data confidentiality and trial registration will also be maintained. Study Management This study will be conducted in coordination with the Provincial Health Training Center, Provincial Health Directorate and provincial hospitals of Lumbini province and led by a team of experts in newborn health, research and epidemiology. Overall, this study addresses critical gaps in newborn care in Nepal by testing a context-specific, skill-based intervention. The study has the potential to improve provider performance, enhance quality of care, and significantly reduce preventable neonatal deaths in resource limited settings in Nepal and elsewhere globally. Expected outcome and measures Key outcomes include provider knowledge, confidence, and clinical skills assessed through structured questionnaires and Objective Structured Clinical Examinations (OSCEs). These will measure both routine newborn care and management of non-breathing infants, along with KMC implementation.

Advanced Wireless Sensors for Neonatal Care in the Delivery Room

The goals of this observational study is to assess whether a new advanced wireless skin sensor vital sign monitoring system can effectively monitor the vital signs of healthy newborn infants (≥ 35 weeks gestational age). The main aims of this Study are to: 1. Assess feasibility 2. Evaluate safety 3. Determine accuracy of the wireless monitoring system, compared to the standard of care wired vital sign monitoring system, immediately after delivery and for the first 2h of age in the obstetrical center under unsupervised parents' care. The newborn infants participating in the Study will have both vital sign monitoring systems placed on their chest and limb. Their vital signs will be monitored for 2h consecutively.

Cooling in Mild Encephalopathy

The goal of this randomised control trial is to establish the safety and efficacy of whole-body hypothermia for babies with mild hypoxic ischaemic encephalopathy, inform national and international guidelines, and establish uniform practice across the NHS. The main questions it aims to answer are: 1. Does whole-body cooling (33.5±0.5°C) initiated within six hours of birth and continued for 72 hours, improve cognitive development at 24 (±2) months of age after mild neonatal encephalopathy compared with normothermia (37±0.5°C)? 2. Does a prospective trial-based economic evaluation support the provision of cooling therapy for mild encephalopathy in the NHS on cost-effectiveness grounds? Participants will have the following interventions: * Randomisation into one of the following groups * Whole body hypothermia group * Targeted normothermia group * Bayley Scales of Infant and Toddler Development 4th Edition (Bayley-IV) examination at 24 (±2) months of age. Researchers will compare the mean Cognitive Composite Scale score from the Bayley IV examination between the two groups.

Fetal Assessment of the Myocardium and Evaluation of the Neonate

FAME-n aims to improve perinatal care by introducing new approaches to fetal and neonatal heart assessment. Better identification of high-risk deliveries requiring intervention will reduce perinatal asphyxia-related illness and death. Neonatal hemodynamics may be improved by early detection of instability of the heart and circulation. Innovative use of technology enables characterization of normal and abnormal cardiovascular transition in a significantly larger number of fetuses and newborn infants than what was previously possible. The methods used may have broad generalizability and applicability in perinatal, neonatal and pediatric medicine. In September 2023, the project was expanded with an obstetric arm called Epidural analgesia: Fetal Oxygenation and Maternal Oxygenation (Epi-FOMO). In Epi-FOMO, the relationship between maternal breathing and arterial blood gases during labour, and umbilical cord blood gases and neonatal outcomes (as specified in FAME-n) will be investigated.

Is Feeding During Therapeutic Hypothermia Safe and Can Improve Outcomes in Infants With Hypoxic-ischaemic Encephalopathy

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic-ischaemic encephalopathy (HIE) born at 35 weeks or more of gestation. Many neonatal units do not use enteral feeding during TH, in fear of increased risk of complications. Withholding enteral feedings during TH lacks supporting evidence. The aim of the study is to determine if enteral feeding during TH in patients with HIE is safe and assess its effects. Investigators will perform multicenter randomized controlled study in level III neonatal intensive care units on infants qualified for TH. Infants will be randomized into 2 groups: (1) unfed during 72 hours of TH; (2) fed group, which will start receive enteral feeding with mother milk or human donor breast milk at 10 ml/kg/day during first day of TH, 20 ml/kg/day during second day, 30 ml/kg/day during third day. The primary outcome will be (1) combined necrotizing enterocolitis or death, (2) length of hospital stay. The secondary outcomes will be (1) time to full enteral feeding, (2) late-onset sepsis, (3) Test of Infant Motor Performance scoring, (4) MRI scoring, (5) MR spectroscopy parameters.

Erythropoietin for Neonatal Encephalopathy in LMIC (EMBRACE Trial)

One million babies die, and at least 2 million survive with lifelong disabilities following neonatal encephalopathy (NE) in low and middle-income countries (LMICs), every year. Cooling therapy in the context of modern tertiary intensive care improves outcome after NE in high-income countries. However, the uptake and applicability of cooling therapy in LMICs is poor, due to the lack of intensive care and transport facilities to initiate and administer the treatment within the six-hours window after birth as well as the absence of safety and efficacy data on hypothermia for moderate or severe NE. Erythropoietin (Epo) is a promising neuroprotectant with both acute effects (anti-inflammatory, anti-excitotoxic, antioxidant, and antiapoptotic) and regenerative effects (neurogenesis, angiogenesis, and oligodendrogenesis),which are essential for the repair of injury and normal neurodevelopment when used as a mono therapy in pre-clinical models (i.e without adjunct hypothermia). The preclinical data on combined use of Eythropoeitin and hypothermia is less convincing as the mechanisms overlap. Thus, the HEAL (High dose erythropoietin for asphyxia and encephalopathy) trial, a large phase III clinical trial involving 500 babies with with encephalopathy reported that that Erythropoietin along with hypothermia is not beneficial. In contrast, the pooled data from 5 small randomized clinical trials (RCTs) (n=348 babies), suggests that Epo (without cooling therapy) reduce the risk of death or disability at 3 months or more after NE (Risk Ratio 0.62 (95% CI 0.40 to 0.98). Hence, a definitive trial (phase III) for rigorous evaluation of the safety and efficacy of Epo monotherapy in LMIC is now warranted.