Research

UCSF is one of seven clinical centers participating in collaborative clinical trials in pediatric critical care medicine through the CPCCRN network. CPCCRN sponsored studies in which UCSF participates include:

CPCCRN Core Data Project (CCDP) – a project to develop an automated electronic medical data pipeline and database to be used for hypothesis generation, study design and preliminary power analyses. The study gathers information on all PICU discharges from the network clinical centers.

ICU Resus – a step wedge randomized clinical trial to investigate the impact of an ICU bundle for in hospital cardiac arrests and resuscitation. The study focuses on CPR education and quality improvements with physiologic endpoints for CPR quality. The study tests the hypothesis that implementation of a CPR bundle can improve survival with good neurologic function. 

Life after Pediatric Sepsis (LAPSE) – is a prospective observational study to describe short and long term outcomes among a modern cohort of children surviving septic shock. This study is completed and data are being prepared for publication.

Inhaled Nitric Oxide Use in PICU (iNO) – is a prospective observational study of contemporary use of iNO in the PICU. The study will provide essential data to determine if a randomized prospective trial of iNO use in pediatric acute lung injury is feasible and warranted.

Microbiome, Virome, and Host Responses Preceding Ventilator-Associated Pneumonia (VAP) – is a prospective longitudinal study of mechanically ventilated children with systemic bacterial and viral analyses of the respiratory tract. The study uses cutting evaluation of the microbiome and proteome to determine if changes predict ventilator associated pneumonia.

PALISI is a network with representation from over 70 PICUs in North America and Europe with the goal of collaborating to identify supportive, preventive, and therapeutic strategies for acute lung injury, sepsis, multi-organ failure, and other acute, life threatening pulmonary or systemic inflammatory syndromes that affect infants and children. UCSF has been a key member since 2004 and actively participates at the primary conferences and within several sub-committees, including BloodNet, Pedal (focusing on use of large database resources), and HSCT (bone marrow transplant focused research), and Global Health.
PALISI supported studies in which UCSF participates include:

Age of Blood in Children (ABC PICU) – a multicenter double blinded randomized clinical trial comparing the risk of multi-organ dysfunction syndrome between critically ill children transfused with red blood cells of decreased storage age versus those transfused standard issue RBCs.

UCSF has created a multi-specialty research program to understand brain development, risk factors for brain injury, and targets for intervention to optimize outcomes in children with congenital heart disease: https://pedheartbrain.ucsf.edu

Cardiac MRI Study – This two-center observational study is using advanced magnetic resonance imaging (MRI) to understand how brain development is affected by congenital heart disease (CHD). MRI’s are obtained after obtaining informed consent from the mother when a fetus has been prenatally diagnosed with CHD, or following a diagnosis of CHD after birth. Studies are performed between 30-36 weeks of fetal gestation and before and after surgery. Enrolled subjects are then followed for neurodevelopmental assessment at 1, 2.5, 4 and 8 years. This study has enrolled more than 100 newborns since 2002, with many important findings reported in over 12 publications. For more information about this study or related studies of birth asphyxia, prematurity and fetal development see http://www.radiology.ucsf.edu/research/labs/baby-brain  

UCSF is a participating center in PC⁴, a clinical registry that collects data on patients with primary cardiac disease admitted to the cardiac ICU of participating hospitals to support research and quality improvement initiatives.

The Pediatric Pulmonary Hypertension group at UCSF contributes data to both the Pediatric Pulmonary Hypertension Network Registry and the Pulmonary Hypertension Association Registry and in addition has an active research program, which includes several clinical studies: 

Obesity in Fontan patients: This observational study looks at the interaction between obesity and endovascular function in patients with Fontan physiology and the impact on outcome.

MicroRNA in pulmonary hypertension: This study aims to determine if specific MicroRNA patterns correlate with the severity of pulmonary hypertension and its reactivity to acute vasodilator testing.

Cardiac catheterization versus echocardiogram in pulmonary hypertension: This study compares echocardiographic parameters of pulmonary hypertension with cardiac catheterization data in different underlying disease processes.

Subcutaneous Remodulin for pediatric pulmonary hypertension: A descriptive multi-centered study on the use of subcutaneous remodulin for the treatment of pediatric pulmonary hypertension.

BNP as predictor of response to iNO: This study aims to enroll pediatric patients for whom iNO therapy is initiated for any reason and correlate BNP levels pre- and post-initiation of iNO to response, using a variety of clinical outcome measures. 

Metabolic markers in infants with persistent pulmonary hypertension of the newborn: This is an exploratory study using newborn screening data of term and near-term infants to identify differences in metabolomic patterns in infants who suffer from PPHN compared to controls.

VPS database study: This observational study characterizes hospital course and outcomes of children with primary and secondary pulmonary hypertension admitted to the ICU, using the VPS database. As a secondary aim, this study uses the VPS database to develop a predictive score for patients with pulmonary hypertension admitted to the ICU.

Pathogen Identification in Pediatric Hematopoietic Stem Cell Transplant Patients with Suspected Lower Respiratory Tract Infection

This is a UCSF-initiated, multicenter study of children who have undergone stem cell transplantation, also known as bone marrow transplantation, and have subsequently developed respiratory dysfunction. This study seeks to improve diagnosis of infectious and alloreactive lung injury by performing metagenomic next generation sequencing on bronchoalveolar lavage in order to identify missed pathogens and define high-risk subgroups according to patterns of gene expression. This study is funded by the Pediatric Blood and Marrow Transplant Foundation and the NIH Eunice Kennedy Shriver National Institute of Child Health and Development. 

Heart and Lung Failure Insulin Titration Trial (HALF-PINT) – UCSF was one of 35 centers participating a randomized controlled trial to determine if tight glucose control would improve outcomes in critical ill children requiring mechanical ventilation or vasoactive support. This trial was stopped early owing to a low likelihood of benefit and evidence of the possibility of harm.

Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients (THAPCA) Trial

UCSF was one of 37 centers participating in this multicenter randomized trial of hypothermia after cardiac arrest. This study tested the effect of therapeutic hypothermia compared with normothermia on survival rates and risk of brain injury in infants and children who experience a cardiac arrest both in and out of the hospital. For more information about this study see: http://www.thapca.org/index.html or view results from the out of hospital trial.

Protocolized Sedation vs. Usual Care in Pediatric Respiratory Failure (RESTORE) – UCSF was one of 17 sites in this cluster randomized trial testing the effects of a protocol that included targeted sedation, arousal assessments, extubation readiness testing and sedation management versus usual care on duration of mechanical ventilation. Read the results from this study.

Effect of Prone Positioning on Outcomes in Children with Acute Lung Injury (PRONE) – UCSF was the leading enrolling site out of seven PICUs in this randomized, prospective trial of prone positioning during pediatric ARDS. View results from this study.