Pediatric Critical Care Clinical Research

ARRC 

Azithromycin Treatment for Respiratory Syncytial Virus-induced Respiratory Failure in Children

• Summary: The overarching hypothesis of the ARRC trial is that administration of Azithromycin (AZM) during acute, Respiratory Syncytial Virus (RSV)-induced respiratory failure will be beneficial, mediated through the matrix metalloproteinase (MMP)-9 pathway. The proposed study will be a randomized, double-blinded, placebo-controlled Phase III trial to examine the efficacy of AZM therapy relative to placebo in reducing RSV-related morbidity. Patients will be recruited during acute hospitalization and admission to the ICU at 10 pediatric hospitals. The target population selected is pediatric patients with severe RSV lung disease as defined by need for ICU management and intensive respiratory support.

P-ICECAP 

Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP)

• Summary:This is a multicenter trial to establish the efficacy of cooling and the optimal duration of induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest. The study team hypothesizes that longer durations of cooling may improve either the proportion of children that attain a good neurobehavioral recovery or may result in better recovery among the proportion already categorized as having a good outcome.

PRECISE 

Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS

• Summary: The TRIPS study is a prospective, multi-center, double-blind, adaptively randomized, placebo-controlled clinical trial of the drug anakinra for reversal of moderate to severe hyperinflammation in children with sepsis-induced multiple organ dysfunction syndrome (MODS). Eligible subjects will undergo centralized immunophenotyping on day 2 of MODS. Subjects without immunoparalysis (a whole blood ex vivo LPS-induced TNF-alpha production capacity < 200 pg/ml) and a serum ferritin level of 500 - 2,000 ng/ml or a serum C-reactive protein (CRP) ≥ 4 mg/dl will be eligible for randomization, along with subjects with a serum ferritin level of 2,000 - 10,000 ng/ml regardless of their TNF-alpha response. Eligible subjects will receive intravenous (IV) anakinra at a dose of 4, 8, 12, or 16 mg/kg/day or placebo for 7 days.

SHIPSS 

Stress Hydrocortisone in Pediatric Septic Shock

• Summary: SHIPSS is a multi-institutional, prospective, controlled, randomized, double-blinded interventional trial that will examine the potential benefits and risks of adjunctive hydrocortisone prescribed for children with fluid and vasoactive-inotropic refractory septic shock. It is hypothesized that adjunctive hydrocortisone will significantly reduce the incidence of new and progressive organ dysfunction (primary outcome) and proportion of children with poor outcomes, defined as death or severely impaired health-related quality of life (HRQL) (secondary outcome), as assessed at 28 days following study enrollment (randomization).

AMPLE 

Assessment of MODS and PersonaLized Exposures of Antibiotics

• Summary: The AMPLE study is a prospective, observational study investigating how standard antibiotic dosing affects children with multiple organ dysfunction syndrome (MODS). It aims to understand how MODS and immunoparalysis influence antibiotic pharmacokinetics and the ability to reach therapeutic drug levels. The study also explores the potential for precision dosing tools, incorporating renal biomarkers, to improve treatment outcomes in this population.

ASCEND 

ARDS in Children and ECMO initiation strategies impact on Neuro-Developments

• Summary: The ASCEND study is a multicenter investigation evaluating outcomes in 550 children with severe pediatric acute respiratory distress syndrome (PARDS) treated with standard extracorporeal membrane oxygenation (ECMO) support. It focuses on understanding real-world ECMO practices and their effects on ventilator-free days, functional status, and quality of life. The study aims to generate evidence to guide clinical decision-making and improve outcomes for children with severe PARDS.

BREATH 

Better Respiratory Evaluation & Analysis using Tandem Host/Microbe Metagenomics

• Summary: The BREATH study is a multicenter, prospective observational cohort study of critically ill children with acute respiratory failure requiring mechanical ventilation for more than 24 hours. It aims to validate and develop machine learning classifiers using host gene expression, microbial data, and proteomics from tracheal aspirates, nasopharyngeal swabs, and blood samples to differentiate lower respiratory tract infections (LRTI) from non-infectious causes. The ultimate goal is to create rapid diagnostic tools to improve antimicrobial stewardship and patient outcomes in pediatric critical care.

Overcoming COVID-19 

Understanding Coronavirus Disease 2019 (Overcoming COVID-19) in US Children

• Summary: The Overcoming COVID-19 study is an active, multicenter prospective cohort study of hospitalized children, adolescents, and young adults with severe acute respiratory illness (SARI), with a focus on SARS-CoV-2 infection and related complications. The study aims to investigate the epidemiology, immune responses, and long-term outcomes of COVID-19 and multisystem inflammatory syndrome in children (MIS-C), while also examining genetic factors, biomarkers, and vaccine-related effects. By establishing a biobank of clinical samples, the study seeks to advance understanding of COVID-19 pathophysiology and guide future prevention and treatment strategies for critically ill pediatric populations.

Pedi-EquiOx

Prospective Clinical Study to Evaluate the Accuracy of Pulse Oximeters in Children with Darker Skin Pigmentation

• Summary: The Pedi-EquiOx study is a prospective, multicenter observational study evaluating the accuracy of FDA-cleared pulse oximeters in children of varying skin pigmentation. It aims to determine if pulse oximeters systematically overestimate oxygen saturation in children with darker skin, potentially contributing to delayed clinical care and health disparities. By incorporating objective skin pigmentation measures, simultaneous SpO₂ and SaO₂ readings, and detailed clinical variables, the study seeks to generate evidence that informs future medical device standards and reduces bias in pediatric care.

PICFLU

Pediatric Intensive Care Influenza Study

• Summary: The PICFLU study is a multicenter, prospective observational study investigating the immunobiology of severe influenza-related critical illness in children and young adults hospitalized in pediatric intensive care units. It aims to identify clinical outcomes, immune responses, and genetic factors that influence susceptibility, severity, and recovery from influenza-associated lower respiratory tract infections. By integrating clinical data, biospecimen analyses, and long-term follow-up, the study seeks to define risk stratification tools and therapeutic targets to improve outcomes and guide personalized care in young patients with severe influenza.

TROPICS 

Transfusion and Organ Dysfunction in Pediatric Septic Shock

• Summary: The TROPICS study is a multicenter, prospective observational cohort study focused on critically ill children with septic shock, aiming to improve decision-making around red blood cell (RBC) transfusions. The study seeks to develop data-driven, personalized transfusion strategies by identifying clinical, hemodynamic, immunologic, and blood product factors associated with outcomes like organ dysfunction and mortality. By integrating advanced machine learning techniques with biomarker analysis, TROPICS aims to move beyond traditional hemoglobin-based transfusion thresholds and establish individualized, physiology-based transfusion guidelines to enhance care and reduce harm in pediatric septic shock.

QUELIMMUNE Surveillance Registry

Pediatric and Young Adults Selective Cyptopheretic Device (SCD-PED) for Critically Ill Children with Acute Kidney injury: A Humanitarian Device Exemption (HDE)

• Summary: The QUELIMMUNE Surveillance Registry is a prospective, multicenter observational study designed to monitor the safety of QUELIMMUNE (SCD-PED), a selective cytopheretic device approved under a Humanitarian Device Exemption (HDE) for pediatric patients (≥10kg, ≤22 years) with acute kidney injury (AKI) due to sepsis requiring renal replacement therapy (RRT). The registry focuses on collecting safety outcomes, specifically comparing the incidence of new bloodstream infections within 28 days of treatment initiation against a matched cohort of CKRT patients with sepsis who did not receive QUELIMMUNE. This real-world surveillance aims to inform safety monitoring and optimize the clinical use of QUELIMMUNE in critically ill pediatric populations.