Clinical trial NCT00814099: Sedation Management in Pediatric Patients With Acute Respiratory Failure (The RESTORE Study)
Official title: Sedation Management in Pediatric Patients With Acute Respiratory Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Insufficiency
Respiratory Distress Syndrome, Newborn
Lung Diseases
Keywords: Acute Respiratory Failure
Acute Lung Injury
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-12-23
Enrollment: 2449
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: People with acute respiratory failure usually require the use of an artificial breathing machine, known as a mechanical ventilator. Sedative medications, which help keep people calm and reduce anxiety, are often prescribed for children who are on mechanical ventilators. However, the longer that sedative medications are used, the longer a child may need to remain on mechanical ventilation. This study will evaluate the effectiveness of a team approach to sedation management that aims to reduce the number of days that children with acute respiratory failure require mechanical ventilation.

Detailed description: People who are hospitalized for acute respiratory failure are typically supported on mechanical ventilation, which delivers oxygen and a continuous level of pressure to the damaged lungs. Over 90% of infants and children supported on mechanical ventilation receive some form of sedation medication, which helps keep them safe, calm, and comfortable. Unfortunately, the use of sedation medications may prolong the duration of mechanical ventilation, which can lead to an increased risk for pneumonia and other complications.

Recent studies among adults in intensive care units (ICUs) have shown that when doctors and nurses work together as a team to manage the use of sedation medication, patients are taken off mechanical ventilation sooner and with fewer side effects. This team strategy includes the following:

* Training and discussion between doctors and nurses regarding which sedative medications should be used
* Having doctors and nurses jointly identify the patient's progress and a daily sedation medication goal for the patient
* Having nurses use a decision-making tool to help guide changes in a patient's sedative medication dose
* Keeping track of patient care, which allows doctors and nurses to evaluate the effectiveness of how they manage each patient's sedative medication use

This study will examine the use of the sedation management strategy for infants and children in pediatric ICUs who have acute respiratory failure and require mechanical ventilation. The purpose of the study is to evaluate whether this team approach to sedation medication management is more effective than the usual approach at reducing the amount of time children remain on mechanical ventilators. Study researchers will also examine the cost-effectiveness of this approach and associated quality of life factors.

All participants will be enrolled within 24 hours of starting mechanical ventilation and will be monitored until they receive their last dose of sedative medication, hospital discharge, or Day 28 (whichever comes first). During a 3-month baseline period, all participating pediatric ICUs will provide their usual sedation management, and study researchers will review participants' medical records on a daily basis. Each pediatric ICU will then be randomly assigned to either the control group or the team approach group. Pediatric ICUs in the control group will continue to provide usual care for sedation management. Pediatric ICUs in the team approach group will implement the team approach sedation management guidelines. For both groups, pain and sedation levels will be monitored daily, and study researchers will review participants' medical records on a daily basis, too. Six months after hospital discharge, half of the participants and their parents will complete a follow-up survey and take part in a telephone interview to assess quality of life, psychological factors, and health-related resource use.

Eligibility criteria: Inclusion Criteria:

* At least 2 weeks of age (and at least 42 weeks post-menstrual age) and less than 18 years of age
* Intubated and mechanically ventilated for acute lung disease

Exclusion Criteria:

* Cyanotic heart disease with unrepaired or palliated right to left intracardiac shunt
* History of single ventricle at any stage of repair
* Congenital diaphragmatic hernia or paralysis
* Primary pulmonary hypertension
* Critical airway or anatomical obstruction of the lower airway
* Ventilator dependent upon pediatric ICU admission
* Neuromuscular respiratory failure
* Spinal cord injury above the lumbar region
* Pain managed by patient-controlled analgesia or epidural catheter
* Patient transferred from an outside ICU where sedatives had already been administered for more than 24 hours
* Family or medical team has decided not to provide full support
* Enrolled in any other critical care interventional clinical trial concurrently or in the 30 days before study entry
* Known allergy to any of the study medications
* Pregnancy

Primary outcomes:
measure: Duration of mechanical ventilation
timeFrame: Measured from the time of endotracheal intubation to the end of scheduled sedation therapy, hospital discharge, or Day 28 (whichever comes first)
Secondary outcomes:
measure: Time to recovery of acute respiratory failure
timeFrame: Measured from the time of endotracheal intubation to when participants first meet the criteria to be tested for extubation readiness
measure: Duration of weaning from mechanical ventilation
timeFrame: Measured from the time participants meet the criteria to be tested for extubation readiness until the time of the first successful extubation (defined as extubation for more than 24 hours)
measure: Occurrence of adverse events
timeFrame: Measured for the duration of the study
measure: Detection of life-threatening neurological events
timeFrame: Measured for the duration of the study
measure: Total sedative exposure
timeFrame: Measured for the duration of the study
measure: Occurrence of iatrogenic withdrawal symptoms
timeFrame: Measured for the duration of the study
measure: Pediatric ICU and hospital length of stay
timeFrame: Measured for the duration of the study
measure: Hospital costs
timeFrame: Measured for the duration of the study
measure: Study implementation costs and cost-effectiveness
timeFrame: Measured for the duration of the study
measure: In-hospital mortality
timeFrame: Measured for the duration of the study
measure: Post-discharge quality of life and emotional health
timeFrame: Measured 6 months after pediatric ICU discharge
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Tucson
country: United States
facility: University Medical Center, The University of Arizona
state: Arizona
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Salter Packard Children's Hospital at Stanford
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Children's Hospital at University of California San Francisco Medical Center
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Children's Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours/Alfred I. duPont Hospital for Children
state: Delaware
city: Miami
country: United States
facility: Holtz Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Florida Hospital for Children
state: Florida
city: Chicago
country: United States
facility: Children's Memorial Hospital, Chicago
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Hope Children's Hospital
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Hospital for Children
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Children's Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: C. S. Mott Children's Hospital of the University of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital, Kansas City
state: Missouri
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: Durham
country: United States
facility: Duke Children's Hospital and Health Center
state: North Carolina
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carell, Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: Medical City Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
Study officials:
affiliation: University of Pennsylvania
name: Martha A.Q. Curley, RN, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Director, Statistics and Data Coordinating Center; Children's Hospital Boston
name: David Wypij, PhD
role: STUDY_DIRECTOR
References:
citation: Monteiro ACC, Flori H, Dahmer MK, Sim MS, Quasney MW, Curley MAQ, Matthay MA, Sapru A; BALI Study Investigators of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Thrombomodulin is associated with increased mortality and organ failure in mechanically ventilated children with acute respiratory failure: biomarker analysis from a multicenter randomized controlled trial. Crit Care. 2021 Aug 3;25(1):271. doi: 10.1186/s13054-021-03626-1.
citation: Kopp W, Gedeit RG, Asaro LA, McLaughlin GE, Wypij D, Curley MAQ; Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Study Investigators. The Impact of Preintubation Noninvasive Ventilation on Outcomes in Pediatric Acute Respiratory Distress Syndrome. Crit Care Med. 2021 May 1;49(5):816-827. doi: 10.1097/CCM.0000000000004819.
citation: Natale JE, Asaro LA, Joseph JG, Ulysse C, Ascenzi J, Bowens C, Wypij D, Curley MAQ; RESTORE Study Investigators. Association of Race and Ethnicity with Sedation Management in Pediatric Intensive Care. Ann Am Thorac Soc. 2021 Jan;18(1):93-102. doi: 10.1513/AnnalsATS.201912-872OC.
citation: Curley MAQ, Gedeit RG, Dodson BL, Amling JK, Soetenga DJ, Corriveau CO, Asario LA, Wypij D; RESTORE Investigative Team. Methods in the design and implementation of the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial. Trials. 2018 Dec 17;19(1):687. doi: 10.1186/s13063-018-3075-8.
citation: Watson RS, Asaro LA, Hertzog JH, Sorce LR, Kachmar AG, Dervan LA, Angus DC, Wypij D, Curley MAQ; RESTORE Study Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Long-Term Outcomes after Protocolized Sedation versus Usual Care in Ventilated Pediatric Patients. Am J Respir Crit Care Med. 2018 Jun 1;197(11):1457-1467. doi: 10.1164/rccm.201708-1768OC.
citation: Lebet R, Hayakawa J, Chamblee TB, Tala JA, Singh N, Wypij D, Curley MAQ. Maintaining Interrater Agreement of Core Assessment Instruments in a Multisite Randomized Controlled Clinical Trial: The Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Trial. Nurs Res. 2017 Jul/Aug;66(4):323-329. doi: 10.1097/NNR.0000000000000224.
citation: Natale JE, Lebet R, Joseph JG, Ulysse C, Ascenzi J, Wypij D, Curley MAQ; Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Study Investigators. Racial and Ethnic Disparities in Parental Refusal of Consent in a Large, Multisite Pediatric Critical Care Clinical Trial. J Pediatr. 2017 May;184:204-208.e1. doi: 10.1016/j.jpeds.2017.02.006. Epub 2017 Mar 2.
citation: Curley MA, Wypij D, Watson RS, Grant MJ, Asaro LA, Cheifetz IM, Dodson BL, Franck LS, Gedeit RG, Angus DC, Matthay MA; RESTORE Study Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators Network. Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: a randomized clinical trial. JAMA. 2015 Jan 27;313(4):379-89. doi: 10.1001/jama.2014.18399.