Clinical trial NCT01415180: Life After Pediatric Sepsis Evaluation
Official title: Life After Pediatric Sepsis Evaluation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Septic Shock
Keywords: sepsis
health related quality of life
functional status
chronic comorbid conditions
organ dysfunction
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: The National Collaborative Pediatric Critical Care Research Network
name: Children's Hospital Los Angeles
name: Children's Hospital of Michigan
name: Children's Hospital of Philadelphia
name: University of Pittsburgh
name: University of California, Los Angeles
name: C.S. Mott Children's Hospital
name: Children's National Research Institute
name: Phoenix Children's Hospital
name: Texas A&M University
First posted: 2011-08-11
Enrollment: 389
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children aged 0-18 admitted to a PICU for septic shock

Brief summary: Sepsis represents the leading cause of childhood mortality worldwide. However, as distinct from adult medicine, there exists a large knowledge gap regarding long term health related quality of life (HRQL) and functional status (FS) following pediatric sepsis. This lack of sepsis outcomes data is critical because failure to identify children at risk for sepsis associated HRQL/FS deterioration may delay delivery of crucial rehabilitation medicine efforts to facilitate recovery. Moreover, failure to identify mechanisms of sepsis associated HRQL/FS deterioration may impede development of novel, effective interventions for these children. For the first time the LAPSE investigation will quantify deterioration of HRQL/FS among children surviving sepsis. We will measure the incidence, magnitude and duration of HRQL/FS alterations associated with pediatric septic shock, and examine clinical, sociodemographic, and parent/family factors potentially associated with such adverse outcomes. Because sepsis affects a heterogeneous group of children, long term morbidity associated with sepsis likely depends on premorbid health status and parent, family and home characteristics, as well as children's clinical course during sepsis critical illness. Mechanisms underlying adverse sepsis outcomes among children are poorly understood at this time. Clinically multiple organ dysfunction syndrome (MODS) has been clearly linked to sepsis mortality. To begin to understand pathophysiology underlying pediatric sepsis morbidity, this investigation will seek to identify evidence for association of HRQL/FS alterations following sepsis with intensity and duration of sepsis mediated organ dysfunction as well as with pre-existing comorbidities and parent, family, and home characteristics. The long-term goal of this research program is to timely identify children at high risk of sepsis mediated HRQL/FS deterioration and ultimately to design effective interventions to minimize such risk. The primary objectives of this investigation are to comprehensively characterize HRQL/FS trajectory and to critically examine the potential role of sepsis mediated organ dysfunction as well as pre-existing comorbidities and parent, family, and home characteristics as risk factors for the adverse outcomes. The central hypothesis is that intensity of sepsis organ dysfunction will predict magnitude of HRQL/FS deterioration. We also hypothesize that the trajectory towards baseline HRQL/FS following the sepsis event will also depend on pre-existing co-morbidities and parent, family, and home, and characteristics. Knowledge of these potential mechanisms will ultimately facilitate development of targeted interventions to maximize HRQL/FS among children surviving sepsis.

Detailed description: In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity and critical illness factors associated with these outcomes for children encountering community-acquired septic shock.

Design: Prospective, cohort-outcome study, conducted 2013-2017. Setting: Twelve academic pediatric intensive care units (PICUs) in the United States.

Patients: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. Interventions: Demographic, infection, and illness severity data were collected at PICU admission. Organ dysfunction and resource utilization data were collected during PICU stay. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale.

Eligibility criteria: Inclusion Criteria:

* Age 44 weeks EGA to 18 years
* Admitted to the PICU for the sepsis event
* Evidence of SIRS including fever/ hypothermia and leukocytosis/leukopenia
* Documented or suspected infection
* Cardiovascular organ dysfunction with need for vasoactive-inotropic support

Exclusion Criteria:

* Lack of commitment to aggressive sepsis therapy OR
* Ward of the state OR
* Sepsis event associated with a PICU-acquired nosocomial infection OR
* Parents do not speak English or Spanish OR
* Previously enrolled in the LAPSE study
* Enrollment not possible within 12 hours of PICU admission

Primary outcomes:
measure: Specific Aim 1: Measure alterations in HRQL/FS longitudinally among children with septic shock.
timeFrame: Baseline, PICU discharge, 1, 3, 6, 12 months following PICU admission for sepsis
Secondary outcomes:
measure: Specific Aim 2: Determine the association between the magnitude of septic shock related HRQL/FS deterioration with validated measures of sepsis-mediated organ dysfunction.
timeFrame: Baseline, PICU discharge, 1, 3, 6, 12 months following PICU admission for sepsis
measure: Specific Aim 3: Describe the association between longitudinal changes in HRQL/FS following septic shock with measures of parent, family, and home characteristics and pre-existing comorbidities.
timeFrame: Baseline, PICU discharge, 1, 3, 6, 12 months following PICU admission for sepsis
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital
state: California
city: Washington
country: United States
facility: National Children's Hospital
state: District of Columbia
city: Ann Arbor
country: United States
facility: Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pittsburgh Children's Hospital
state: Pennsylvania
city: College Station
country: United States
facility: Texas A&M University
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Jerry J. Zimmerman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zimmerman JJ, Banks R, Berg RA, Zuppa A, Newth CJ, Wessel D, Pollack MM, Meert KL, Hall MW, Quasney M, Sapru A, Carcillo JA, McQuillen PS, Mourani PM, Wong H, Chima RS, Holubkov R, Coleman W, Sorenson S, Varni JW, McGalliard J, Haaland W, Whitlock K, Dean JM, Reeder RW; Life After Pediatric Sepsis Evaluation (LAPSE) Investigators. Critical Illness Factors Associated With Long-Term Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock. Crit Care Med. 2020 Mar;48(3):319-328. doi: 10.1097/CCM.0000000000004122.
citation: Zimmerman JJ, Banks R, Berg RA, Zuppa A, Newth CJ, Wessel D, Pollack MM, Meert KL, Hall MW, Quasney M, Sapru A, Carcillo JA, McQuillen PS, Mourani PM, Wong H, Chima RS, Holubkov R, Coleman W, Sorenson S, Varni JW, McGalliard J, Haaland W, Whitlock K, Dean JM, Reeder RW; Life After Pediatric Sepsis Evaluation (LAPSE) Investigators. Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock. Crit Care Med. 2020 Mar;48(3):329-337. doi: 10.1097/CCM.0000000000004123.
citation: Meert KL, Reeder R, Maddux AB, Banks R, Berg RA, Zuppa A, Newth CJ, Wessel D, Pollack MM, Hall MW, Quasney M, Sapru A, Carcillo JA, McQuillen PS, Mourani PM, Chima RS, Holubkov R, Sorenson S, Varni JW, McGalliard J, Haaland W, Whitlock KB, Dean JM, Zimmerman JJ; and the Life After Pediatric Sepsis Evaluation (LAPSE) Investigators. Trajectories and Risk Factors for Altered Physical and Psychosocial Health-Related Quality of Life After Pediatric Community-Acquired Septic Shock. Pediatr Crit Care Med. 2020 Oct;21(10):869-878. doi: 10.1097/PCC.0000000000002374.
citation: Murphy LK, Palermo TM, Meert KL, Reeder R, Dean JM, Banks R, Berg RA, Carcillo JA, Chima R, McGalliard J, Haaland W, Holubkov R, Mourani PM, Pollack MM, Sapru A, Sorenson S, Varni JW, Zimmerman J. Longitudinal Trajectories of Caregiver Distress and Family Functioning After Community-Acquired Pediatric Septic Shock. Pediatr Crit Care Med. 2020 Sep;21(9):787-796. doi: 10.1097/PCC.0000000000002404.
citation: Starr MC, Banks R, Reeder RW, Fitzgerald JC, Pollack MM, Meert KL, McQuillen PS, Mourani PM, Chima RS, Sorenson S, Varni JW, Hingorani S, Zimmerman JJ; Life After Pediatric Sepsis Evaluation (LAPSE) Investigators. Severe Acute Kidney Injury Is Associated With Increased Risk of Death and New Morbidity After Pediatric Septic Shock. Pediatr Crit Care Med. 2020 Sep;21(9):e686-e695. doi: 10.1097/PCC.0000000000002418.