Research

Faculty in the Division of Pediatric Critical Care are actively involved in a variety of basic, translational and clinical research efforts that ultimately aim to improve our understanding of pediatric diseases and our ability to care for critically ill children. For more information, visit the links below:

Critical Care Clinical Trials

 

Our division is currently participating in the following clinical research networks & studies:

Collaborative Pediatric Critical Care Research Network (CPCCRN)

CPCCRN was established in 2004 with funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. UCSF joined the network in the third cycle and is one of seven clinical centers and one data-coordinating center in the CPCCRN network. The goal of the network is to provide infrastructure to pursue well-designed collaborative clinical trials in pediatric critical care medicine. Further information about our network can be found here: http://www.cpccrn.org

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.

Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network.

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). Further information about the network can be found here: http://www.palisi.org.

PALISI supported studies in which UCSF participates include:

Age of Blood in Children (ABC PICU) – is 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. Further information about this trial can be found here: http://abcpicu.wustl.edu/

On-going local investigator sponsored studies:

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

Pediatric Pulmonary Hypertension Clinical Research

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. The object of this study is 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.

Completed Published Multicenter Trials

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 can 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. Further information about this study can be found: https://www.halfpintstudy.org and results from the trial have been published:

Agus MS1, Wypij D1, Hirshberg EL1, Srinivasan V1, Faustino EV1, Luckett PM1, Alexander JL1, Asaro LA1, Curley MA1, Steil GM1, Nadkarni VM1; HALF-PINTStudy Investigators and the PALISI Network. Tight Glycemic Control in Critically Ill Children. N Engl J Med. 2017 Feb 23;376(8):729-741.

https://www.ncbi.nlm.nih.gov/pubmed/28118549

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

UCSF was one of 37 clinical centers across the country participating in this multicenter randomized trial of hypothermia after cardiac arrest. This study tested the efficacy of therapeutic hypothermia compared with normothermia in increasing survival rates and reducing the 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 Results from the out of hospital trial can be found here:

Moler FW, Silverstein FS, Holubkov R, Slomine BS, Christensen JR, Nadkarni VM, Meert KL, Clark AE, Browning B, Pemberton VL, Page K, Shankaran S, Hutchison JS, Newth CJ, Bennett KS, Berger JT, Topjian A, Pineda JA, Koch JD, Schleien CL, Dalton HJ, Ofori-Amanfo G, Goodman DM, Fink EL, McQuillen P, Zimmerman JJ, Thomas NJ, van der Jagt EW, Porter MB, Meyer MT, Harrison R, Pham N, Schwarz AJ, Nowak JE, Alten J, Wheeler DS, Bhalala US, Lidsky K, Lloyd E, Mathur M, Shah S, Wu T, Theodorou AA, Sanders RC Jr, Dean JM; THAPCA Trial Investigators. "Therapuetic Hypothermia after Out-of-hospital Cardiac Arrest in Children" New England Journal of Medicine 25 Apr 2015

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. Results from this study can be found here:

Martha A. Q. Curley, RN, PhD1,2; David Wypij, PhD3,4,5; R. Scott Watson, MD, MPH6,7; Mary Jo C. Grant, APRN, PhD8; Lisa A. Asaro, MS5; Ira M. Cheifetz, MD9; Brenda L. Dodson, PharmD10; Linda S. Franck, RN, PhD11; Rainer G. Gedeit, MD12; Derek C. Angus, MD, MPH7; Michael A. Matthay, MD13 ; for the RESTORE Study Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Protocolized Sedation vs. Usual Care in Pediatric Patients Mechanically Ventilated for Acute Respiratory Failure A Randomized Clinical Trial. JAMA 2015. 

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. Results from this study can be found here:

Martha A. Q. Curley, RN, PhD; Patricia L. Hibberd, MD, PhD; Lori D. Fineman, RN, MS; David Wypij, PhD; Mei-Chiung Shih, PhD; John E. Thompson, RRT; Mary Jo C. Grant, RN, PhD; Frederick E. Barr, MD, MS; Natalie Z. Cvijanovich, MD; Lauren Sorce, RN, MS; Peter M. Luckett, MD; Michael A. Matthay, MD; John H. Arnold, MD Effect of Prone Positioning on Clinical Outcomes in Children With Acute Lung InjuryA Randomized Controlled Trial JAMA 2005