Obstructive Sleep Apnea, Snoring
Conditions
Keywords
Sleep disordered breathing, Sleep apnea, Tonsillectomy, Adenoidectomy, Snoring, Neurobehavioral Manifestations, Obstructive Sleep Apnea Syndrome
Brief summary
The purpose of this research is to determine the effect of adenotonsillectomy surgery (removal of tonsils and adenoids) on obstructive sleep apnea syndrome (OSAS) in children. OSAS can cause health problems including poor growth, high blood pressure, diabetes and behavioral and learning difficulties. Although adenotonsillectomy is the usual treatment for children with OSAS, it is not known with any certainty if the child's OSAS symptoms improve afterwards. This study will help determine if improvement occurs or if it does not. It will also look at whether certain groups, such as children who are overweight or of different ethnicities, are helped by the surgery.
Detailed description
Because adenotonsillectomy is the usual treatment for OSAS, all children in the study will get surgery. However, in order to assess the extent to which adenotonsillectomy surgery improves breathing disturbances and sleep quality in children with OSAS, two groups will be studied. One group will get surgery early (one month after enrollment) and the other group will be re-evaluated for surgery within 7 months of enrollment. Children in both groups will be closely monitored through the 7-8 month study period and sleep and health educational materials will be provided to assist in establishing healthy habits.
Interventions
Standard surgical intervention for treatment of Obstructive Sleep Apnea Syndrome which includes removal of adenoids and tonsils
OTHERWatchful Waiting
Children will reevaluated for adenotonsillectomy (AT) after a 7 month primary monitoring period.
Sponsors
Harvard University
University of Michigan
National Heart, Lung, and Blood Institute (NHLBI)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 5.0 to 9.99 years at time of screening. 2. Diagnosed with Obstructive Sleep Apnea defined as: Obstructive Apnea Index (OAI) ≥ 1 or Apnea Hypopnea Index (AHI) ≥ 2, confirmed on nocturnal, laboratory-based PSG and Parental report of habitual snoring (on average occurring \>3 nights per week). 3. Tonsillar hypertrophy ≥ 1 based on a standardized scale of 0-4: 0 = surgically absent, 1 = taking up \< 25% of the airway, 2 = 25 - 50 % of the airway,3 = 50 - 75 % of the airway, 4 = \> 75% of the airway 4. Deemed to be a surgical candidate for AT by Ear, Nose and Throat specialist (ENT) evaluation.
Exclusion criteria
1. Recurrent tonsillitis defined as: \>3 episodes in each of 3 years, 5 episodes in each of 2 years, or 7 episodes in one year 2. Craniofacial anomalies, including cleft lip and palate or sub-mucosal cleft palate or any anatomic or systemic condition which would interfere with general anesthesia or removal of tonsils and adenoid tissue in the standard fashion 3. Obstructive breathing while awake that merits prompt AT in the opinion of the child's physician 4. Severe OSAS or significant hypoxemia requiring immediate AT as defined by: OAI\>20 or AHI\>30, desaturation defined as oxygen saturation (SaO2) \<90% for more than 2% sleep time 5. Apnea hypopnea indices in the normal range (OAI \< 1 and AHI \<2) 6. Evidence of clinically significant cardiac arrhythmia on PSG: Non-sustained ventricular tachycardia Atrial fibrillation, Second degree atrioventricular (AV) block: Sustained bradycardia \< 40 bpm (\> 2 minutes, Sustained tachycardia \> 140 bpm (\> 2 minutes) 7. Extremely overweight defined as: body mass index \> 2.99 age group and sex-z-score 8. Severe health problems that could be exacerbated by delayed treatment for OSAS Including: Doctor-diagnosed heart disease or cor pulmonale, history of Stage II Hypertension (HTN) defined as \> 99% percentile plus 5 mmHg for either systolic or diastolic, based on the age, gender, and height and/or requiring medication, therapy for failure to thrive or short stature, psychiatric or behavioral disorders requiring or likely to require initiation of new medication, therapy, or other specific treatment. School aged children, parental report of excessive daytime sleepiness defined as unable to maintain wakefulness, at least three times per week, in routine activities in school or home, despite adequate opportunity to sleep. 9. Severe chronic health conditions that might hamper participation including: severe cardiopulmonary disorders, sickle cell anemia, poorly controlled asthma, epilepsy requiring medication, diabetes (type I or type II) requiring medication, conditions likely to preclude accurate polysomnography (e.g. severe uncontrolled pain),mental retardation or enrollment in a formal school Individual Educational Plan (IEP) and assigned to a self-contained classroom for all academic subjects, history of inability to complete cognitive testing and/or score on the Differential Ability Scale (DAS) II of ≤ 55, chronic infection or HIV 10. Known genetic, craniofacial, neurological or psychiatric conditions likely to affect the airway, cognition, or behavior 11. Current use of one or more of the following medications: psychotropics, hypnotics,hypoglycemic agents or insulin,antihypertensives,growth hormone, anticonvulsants,anti-coagulants,daily oral corticosteroids, daily medications for pain 12. Previous upper airway surgery on the nose, pharynx or larynx, including tonsillectomy. Ear surgery and/or pressure equalizing (PE) tubes are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvements in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) From Baseline to 7 Months. | The primary endpoint measure will occur at 7 months following the baseline visit. | The primary outcome was the change in the attention and executive function score on the NEPSY. The change from baseline in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) was compared to 7 months were compared. Scores on the attention and executive-function domain of the Developmental Neuropsychological Assessment (NEPSY) range from 50 to 150, with higher scores indicating better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Apnea Hypopnea Index (AHI) Score From Baseline to 7 Months | 7 months following the baseline visit. | The outcome measure was the change in AHI from baseline to 7 months to determine if there was an improvement in score is associated with improved OSAS (i.e reduction in AHI). The AHI is calculated by dividing the number of apnea events by the number of hours of sleep. The obstructive sleep apnea syndrome was defined as an AHI score of 2 or more events per hour or an obstructive apnea index (OAI) score of 1 or more events per hour. |
| Change in Score of Pediatric Sleep Questionnaire Sleep-related Breathing Disorder Scale | 7 months following baseline. | Scores on the Pediatric Sleep Questionnaire sleep-related breathing disorder scale (PSQ-SRBD) range from 0 to 1, with higher scores indicating greater severity. |
Countries
United States
Participant flow
Recruitment details
Children were recruited at 7 academic sleep centers. Early in the trial the investigator at one center relocated and that center was withdrawn.
Participants by arm
| Arm | Count |
|---|---|
| Early AT Surgery Adenotonsillectomy (AT) - removal of tonsils and adenoids - performed within 4 weeks of the baseline visit.
Adenotonsillectomy (AT) - removal of adenoids and tonsils: Standard surgical intervention for treatment of Obstructive Sleep Apnea Syndrome. | 226 |
| Watchful Waiting Children will be closely monitored and re-evaluated for AT by an otolaryngologist after the primary 7 month monitoring period.
Watchful Waiting: Children will reevaluated for adenotonsillectomy (AT) after a 7 month primary monitoring period. | 227 |
| Total | 453 |
Baseline characteristics
| Characteristic | Early AT Surgery | Watchful Waiting | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 226 Participants | 227 Participants | 453 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.6 Years STANDARD_DEVIATION 1.4 | 6.5 Years STANDARD_DEVIATION 1.4 | 6.6 Years STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 21 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 210 Participants | 206 Participants | 416 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 126 Participants | 123 Participants | 249 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 12 Participants | 27 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) White | 74 Participants | 81 Participants | 155 Participants |
| Region of Enrollment United States | 226 participants | 227 participants | 453 participants |
| Sex: Female, Male Female | 125 Participants | 109 Participants | 234 Participants |
| Sex: Female, Male Male | 101 Participants | 118 Participants | 219 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 166 / 226 | 227 / 227 |
| serious Total, serious adverse events | 7 / 226 | 9 / 227 |
Outcome results
Primary
Improvements in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) From Baseline to 7 Months.
The primary outcome was the change in the attention and executive function score on the NEPSY. The change from baseline in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) was compared to 7 months were compared. Scores on the attention and executive-function domain of the Developmental Neuropsychological Assessment (NEPSY) range from 50 to 150, with higher scores indicating better functioning.
Time frame: The primary endpoint measure will occur at 7 months following the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early AT Surgery | Improvements in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) From Baseline to 7 Months. | 7.1 units on a scale | Standard Deviation 13.9 |
| Watchful Waiting | Improvements in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) From Baseline to 7 Months. | 5.1 units on a scale | Standard Deviation 13.4 |
p-value: 0.16ANCOVA
Secondary
Change in Apnea Hypopnea Index (AHI) Score From Baseline to 7 Months
The outcome measure was the change in AHI from baseline to 7 months to determine if there was an improvement in score is associated with improved OSAS (i.e reduction in AHI). The AHI is calculated by dividing the number of apnea events by the number of hours of sleep. The obstructive sleep apnea syndrome was defined as an AHI score of 2 or more events per hour or an obstructive apnea index (OAI) score of 1 or more events per hour.
Time frame: 7 months following the baseline visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early AT Surgery | Change in Apnea Hypopnea Index (AHI) Score From Baseline to 7 Months | -3.5 Events per hour |
| Watchful Waiting | Change in Apnea Hypopnea Index (AHI) Score From Baseline to 7 Months | -1.6 Events per hour |
Secondary
Change in Score of Pediatric Sleep Questionnaire Sleep-related Breathing Disorder Scale
Scores on the Pediatric Sleep Questionnaire sleep-related breathing disorder scale (PSQ-SRBD) range from 0 to 1, with higher scores indicating greater severity.
Time frame: 7 months following baseline.
Population: There was missing data for some children in the Watchful Waiting group since the Pediatric Sleep Questionnaire was not completed. Hence these numbers are not consistent with the rows in the participant flow module
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early AT Surgery | Change in Score of Pediatric Sleep Questionnaire Sleep-related Breathing Disorder Scale | -0.3 units on a scale | Standard Deviation 0.2 |
| Watchful Waiting | Change in Score of Pediatric Sleep Questionnaire Sleep-related Breathing Disorder Scale | 0 units on a scale | Standard Deviation 0.2 |