Pediatric Adenotonsillectomy Trial for Snoring

Not Applicable

Completed

Conditions: Sleep-Disordered Breathing

Interventions: Behavioral: Watchful Waiting with Supportive Care (WWSC)
Procedure: Early Adenotonsillectomy (eAT)

Registration Number: NCT02562040

Lead Sponsor: Brigham and Women's Hospital

Brief Summary: The purpose of this study is to evaluate the effects of early adenotonsillectomy (eAT) on the behavior, sleep-disordered breathing symptoms and quality of life for children who snore, but do not have obstructive sleep apnea, as well as identify factors that moderate responses to the surgery. Half of participants will receive eAT, while the other half will be observed with watchful waiting and supportive care.

Detailed Description: Adenotonsillectomies are performed more than 500,000 times per year in the United States, and is the most common surgery performed under general anesthesia in children. The majority of surgeries are performed for obstructed breathing rather than for infection or other indications.

The role of adenotonsillectomy (AT) in improving the 7-month neurocognitive, behavioral and health outcomes of children with frank obstructive sleep apnea (OSA) was recently addressed in the Childhood Adenotonsillectomy Trial (CHAT). The results of this rigorous, multicenter, randomized controlled trial provided critically important data indicating that adenotonsillectomy compared to watchful waiting resulted in improved behavior, quality of life, sleep-disordered breathing (SDB) symptoms and polysomnographic parameters.

However, the Childhood Adenotonsillectomy Trial addressed the role of surgery in the minority of operative candidates who have frank obstructive sleep apnea, only one form of sleep disordered breathing on a spectrum that includes a more common phenotype, primary snoring (also termed mild sleep disordered breathing (MSDB)). Mild sleep disordered breathing is characterized by snoring without frank obstruction or gas exchange abnormalities, and has a population prevalence of about 10% in children. Since most surgeries for obstructed breathing are performed for mild sleep disordered breathing rather than obstructive sleep apnea, the next logical question is whether surgery is also effective in improving symptoms and health outcomes in this large group of children.

The Pediatric Adenotonsillectomy Trial for Snoring (PATS) intends to take advantage of a successful collaboration of leaders in sleep medicine, otolaryngology and clinical trials to efficiently leverage experiences from the CHAT trial to evaluate the role of adenotonsillectomy in children with mild sleep disordered breathing while also aiming to resolve uncertainties regarding management approaches for pediatric mild sleep disordered breathing by addressing several critical issues:

1. Assess outcomes important to children and their families, particularly patient-reported outcomes such as behavior, quality of life, and sleep disturbances.

2. Examine differences in treatment responses among children who are at increased risk for mild sleep disordered breathing, such as pre-school children, minorities, and children with asthma or obesity.

3. Evaluate health care utilization of children with mild sleep disordered breathing.

4. Assess moderating influences such as second hand smoke, insufficient sleep, socioeconomic status and family functioning

5. Examine longer term (12 month) outcomes that were not feasible in the Childhood Adenotonsillectomy Trial (CHAT).

These aims have substantial public health significance given the high morbidity of sleep disordered breathing in children.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 459

Inclusion Criteria

Diagnosis of mild sleep-disordered breathing (MSDB) defined as meeting all of the following criteria:
- Caregiver report of habitual snoring that occurs most of the night on at least three nights per week, and has been present for at least three months (on average occurring > 3 nights per week or more half of sleep time) and
- Centrally-scored polysomnogram (PSG) confirming an obstructive apnea index (OAI) <1/hour and apnea-hypopnea index (AHI) ≤3/hour and no oxygen saturation (SpO2) desaturation < 90% in conjunction with obstructive events, confirmed on PSG.
Tonsillar hypertrophy ≥2 based on a standardized scale of 0-4.
Deemed to be a candidate for AT by otolaryngologist (ENT) evaluation (i.e., no technical issues that would be a contraindication for surgery such as submucous cleft palate.)
Primary indication for AT is nocturnal obstructive symptoms (i.e., not recurrent infections or other indications).

Exclusion Criteria

Previous tonsillectomy, including partial tonsillectomy
Recurrent tonsillitis that merits prompt adenotonsillectomy (AT) per the American Academy of Otolaryngology-Head and Neck Surgery Clinical Practice Guidelines (i.e., ≥7 episodes/yr in the past year; ≥5 episodes/year over the past 2 years or ≥3 episodes/yr over the past 3 years.)
Severe obesity (body mass index (BMI) z-score ≥3).
Failure to thrive, defined as either height or weight being below the 5th percentile for age and gender.
Severe chronic health conditions that might hamper participation or confound key variables under study, including but not limited to:
- Severe cardiopulmonary disorders such as cystic fibrosis, and congenital heart disease.
- Bleeding disorders
- Sickle Cell Disease
- Epilepsy requiring medication
- Significant cardiac arrhythmia noted on PSG including: non-sustained ventricular tachycardia, atrial fibrillation, second degree atrioventricular block, sustained bradycardia, or sustained tachycardia.
- Other severe chronic health problems such as diabetes, narcolepsy, and poorly controlled asthma.
- Known genetic, craniofacial, neurological or psychiatric conditions likely to affect the airway, cognition or behavior;
- Current use of psychotropic medication (other than medications for attention deficit hyperactivity disorder, hypnotics, antihypertensives, hypoglycemic agents including insulin, anticonvulsants, anticoagulants, or growth hormone.
- Diagnosis of autism spectrum disorder.
- Intellectual deficit or assigned to a self-contained classroom for all academic subjects.
- History of severe developmental disability or Adaptive Behavior Assessment System (ABAS-3) score ≤60.
Children/caregivers planning to move out of the area within the year.
Children in foster care.
Children/caregivers who do not speak English or Spanish well enough to complete the neurobehavioral measures.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Watchful Waiting with Supportive Care	Watchful Waiting with Supportive Care (WWSC)	All Watchful Waiting with Supportive Care (WWSC) participants will receive information about healthy sleep habits for children and appropriate clinical referrals for management of co-morbidities.
Early Adenotonsillectomy	Early Adenotonsillectomy (eAT)	All Early Adenotonsillectomy (eAT) participants will receive information about healthy sleep habits for children, undergo adenotonsillectomy within 4 weeks of randomization and receive appropriate clinical referrals for management of co-morbidities

Primary Outcome Measures

Name	Time	Method
Change From Baseline to 12 Months in Caregiver-reported Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC) T Score	12 months	The BRIEF GEC section comprises summary measures of behavioral regulation, emotion regulation, and cognitive regulation (BRIEF-2, for children aged 5 to 18 years) or inhibitory self-control, flexibility, and emergent metacognition (BRIEF-P, for preschool-aged children). These scores are linear transformations of the raw scores (mean = 50, sd = 10) where a higher T score indicates a child has a lower capacity to organize and self-regulate.
Change From Baseline to 12 Months in Go-No-Go (GNG) Signal Detection Parameter D-prime (d').	12 months	Performance on combined Go-No-Go (GNG)/Continuous Performance Test (CPT) task was assessed by tracking accuracy responses to targets (fish) and false positive responses to non-targets (sharks). d' is computed for both portions of the task as an assessment of accuracy in making correct detections adjusting for the participant's tendency to respond to non-targets. The adjusted measure is computed by subtracting Z-scores for false positive responses from Z-scores for correct detections. Individual Z-scores were based on a child's performance within same age groups (3-4, 5-6 , and \>=7 years old). Scores ranged across age groups from -0.53 to 3.99 for GNG and -0.61 to 4.35 for CPT. Higher scores reflect better discrimination of targets from non-targets. A value of 4.65 represents 100% accuracy, 0 represents chance performance, and minus scores represent more frequent detection of non-targets than targets, suggesting a child misunderstood instructions or preferred responding to non-targets.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to 12 Months in NIH-Toolbox 9-Hole Pegboard Dexterity Test Time	12 months	Fine motor coordination assessed by the time (in seconds) it takes a child to complete the NIH-Toolbox 9-Hole Pegboard Dexterity Test. Shorter times indicate greater dexterity. The reported value is the average of the dominant and non-dominant hand scores.
Change From Baseline to 12 Months in Child Behavior Checklist (CBCL) Summary Scale T Scores	12 months	Behavior assessed by the change from baseline to 12 months in the caregiver-reported Child Behavior Checklist (CBCL) overall summary score T scores. The T scores are standardized transformations of the raw score (mean = 50, sd = 10), where a higher scores indicate greater problems.
Change From Baseline to 12 Months in Pediatric Sleep Questionnaire: Sleep-Related Breathing Disorder Scale (PSQ-SRBD) Total Score.	12 months	The PSQ-SRBD scale is a 22-item questionnaire which includes three subscales: snoring, daytime sleepiness, and hyperactive behaviors/inattention. The PSQ-SRBD is commonly used to assess sleep-disordered breathing (SDB) risk in pediatric patients, but is also increasingly used to assess symptom burden. Higher scores correspond to greater SDB symptoms and the total range is 0-1
Change From Baseline to 12 Months in Sleepiness Measured by Change in the Epworth Sleepiness Scale (ESS) Modified for Children Summary Score.	12 months	The Epworth Sleepiness Scale (ESS) Modified for Children is an 8-item validated questionnaire which evaluates excessive daytime sleepiness. The wording and questions are revised from the original ESS to be more suitable for children. The total score has a range from 0-24 where higher values indicate greater sleepiness.
Change From Baseline to 12 Months in Pediatric Quality of Life Inventory (PedsQL) Caregiver Reported Total Score and Subscales.	12 months	General quality of life assessed by caregiver reported PedsQL total score and subscores (Psychosocial Health Summary Score \& Physical Health Summary Score). The PedsQL Total Score comprises performance on 4 subscales: emotional functioning, social functioning, school functioning (summarized by the Psychosocial Functioning Score) and physical functioning (summarized by the Physical Functioning score). Scores on all scales range from 0 to 100, with higher scores indicating an increased quality of life.
Change From Baseline to 12 Months in Quality of Life Survey Evaluation of Sleep-Disordered Breathing (OSA-18) Total Score.	12 months	The OSA-18 is a disease-specific QOL survey that captures symptoms across five domains: sleep disturbance, physical suffering, emotional distress, daytime problems, and parent/caretaker concerns. With a Likert 7-point scale, caregivers rate the perceived frequency of 18 OSA-related problems ranging from 1 (none of the time) to 7 (all the time). Scores on each item are summed to produce a total score ranging from 18 to 126. Higher scores correspond to poorer sleep disordered breathing-related QOL, with a score greater than or equal to 60 signifying a clinically meaningful negative impact of sleep disordered breathing on QOL
Change From Baseline to 12 Months in Body Mass Index (BMI) Percentile	12 months	Body Mass Index (BMI) percentile, calculated from the average of triplicate in-clinic height/weight measurements. Percentiles calculated from Centers for Disease Control and Prevention (CDC) BMI-for-age charts.
Change From Baseline to 12 Months in Mean Systolic and Diastolic Blood Pressures (mmHg) Percentile Scores.	12 months	Mean of blood pressures measured in triplicate (to 1.0 mmHg) via automated oscillometric blood pressure cuff. Percentiles calculated respective to height, age and sex (PMID: 18230679).
Change From Baseline to 12 Months in Average Heart Rate	12 months	Average heart rate (beats per minute) calculated from overnight polysomnography

Trial Locations

Locations (7): Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
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Dallas, Texas, United States
University Hospitals-Case Medical Center
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Cleveland, Ohio, United States
Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
University of Michigan Health System
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Ann Arbor, Michigan, United States
Cincinnati Children's Hospital Medical Center
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Cincinnati, Ohio, United States
Children's Hospital of the King's Daughters
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Norfolk, Virginia, United States