Clinical trial NCT00560859: Childhood Adenotonsillectomy Study for Children With OSAS
Official title: A Randomized Controlled Study of Adenotonsillectomy for Children With Obstructive Sleep Apnea Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea
Snoring
Keywords: Sleep disordered breathing
Sleep apnea
Tonsillectomy
Adenoidectomy
Snoring
Neurobehavioral Manifestations
Obstructive Sleep Apnea Syndrome
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Harvard University
name: University of Michigan
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-11-20
Enrollment: 453
Sex: ALL
Minimum age (years): 5
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria
13. Receives Continuous Positive Airway Pressure (CPAP) treatment
14. A parent or guardian who cannot accompany the child on the night of polysomnogram (PSG)
15. A family planning to move out of the area within the year
16. Female participants only: Parental report that child has reached menarche

Primary outcomes:
measure: Improvements in Attention/Executive Domain Index of the Developmental Neuropsychological Assessment (NEPSY) From Baseline to 7 Months.
timeFrame: The primary endpoint measure will occur at 7 months following the baseline visit.
Secondary outcomes:
measure: Change in Apnea Hypopnea Index (AHI) Score From Baseline to 7 Months
timeFrame: 7 months following the baseline visit.
measure: Change in Score of Pediatric Sleep Questionnaire Sleep-related Breathing Disorder Scale
timeFrame: 7 months following baseline.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: St. Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: New York
country: United States
facility: Montefiore Children's Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Harvard University
name: Susan Redline, MD, MPH
role: STUDY_CHAIR
affiliation: University of Pennsylvania
name: Susan Ellenberg, Ph.D.
role: STUDY_DIRECTOR
affiliation: University of Michigan
name: Ron Chervin, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Univeristy of Michigan
name: Bruno Giordani, PH.D.
role: STUDY_DIRECTOR
affiliation: University of Michigan
name: Susan Garetz, MD
role: STUDY_DIRECTOR
affiliation: Cincinnati Children's Hopsital Medical Center (CCHMC)
name: Raouf Amin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Carole Marcus, MBB Ch.
role: PRINCIPAL_INVESTIGATOR
affiliation: Case University School of Medicine; Rainbow Babies & Children's Hospital
name: Carol Rosen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardinal Glennon Children's Medical Center, St. Louis MO
name: Ron Mitchell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Children's Hospital Albert Einstein Med Ctr, NY NY
name: Raanan Arens, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Chilren's Hospital Albert Einstein Med Ctr, NY NY
name: Hiren Muzumdar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital, Boston MA
name: Eliot Katz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yu PK, Radcliffe J, Gerry Taylor H, Amin RS, Baldassari CM, Boswick T, Chervin RD, Elden LM, Furth SL, Garetz SL, George A, Ishman SL, Kirkham EM, Liu C, Mitchell RB, Kamal Naqvi S, Rosen CL, Ross KR, Shah JR, Tapia IE, Young LR, Zopf DA, Wang R, Redline S. Neurobehavioral morbidity of pediatric mild sleep-disordered breathing and obstructive sleep apnea. Sleep. 2022 May 12;45(5):zsac035. doi: 10.1093/sleep/zsac035. Epub 2022 Feb 12.
citation: Snow A, Vazifedan T, Baldassari CM. Evaluation of Nocturnal Enuresis After Adenotonsillectomy in Children With Obstructive Sleep Apnea: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2021 Oct 1;147(10):887-892. doi: 10.1001/jamaoto.2021.2303.
citation: Martin-Montero A, Gutierrez-Tobal GC, Kheirandish-Gozal L, Vaquerizo-Villar F, Alvarez D, Del Campo F, Gozal D, Hornero R. Heart rate variability as a potential biomarker of pediatric obstructive sleep apnea resolution. Sleep. 2022 Feb 14;45(2):zsab214. doi: 10.1093/sleep/zsab214.
citation: Isaiah A, Spanier AJ, Grattan LM, Wang Y, Pereira KD. Predictors of Behavioral Changes After Adenotonsillectomy in Pediatric Obstructive Sleep Apnea: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2020 Oct 1;146(10):900-908. doi: 10.1001/jamaoto.2020.2432.
citation: Hartmann S, Bruni O, Ferri R, Redline S, Baumert M. Cyclic alternating pattern in children with obstructive sleep apnea and its relationship with adenotonsillectomy, behavior, cognition, and quality of life. Sleep. 2021 Jan 21;44(1):zsaa145. doi: 10.1093/sleep/zsaa145.
citation: Hilmisson H, Berman S, Magnusdottir S. Sleep apnea diagnosis in children using software-generated apnea-hypopnea index (AHI) derived from data recorded with a single photoplethysmogram sensor (PPG) : Results from the Childhood Adenotonsillectomy Study (CHAT) based on cardiopulmonary coupling analysis. Sleep Breath. 2020 Dec;24(4):1739-1749. doi: 10.1007/s11325-020-02049-6. Epub 2020 Mar 28.
citation: Isaiah A, Pereira KD, Das G. Polysomnography and Treatment-Related Outcomes of Childhood Sleep Apnea. Pediatrics. 2019 Oct;144(4):e20191097. doi: 10.1542/peds.2019-1097.
citation: Hilmisson H, Lange N, Magnusdottir S. Objective sleep quality and metabolic risk in healthy weight children results from the randomized Childhood Adenotonsillectomy Trial (CHAT). Sleep Breath. 2019 Dec;23(4):1197-1208. doi: 10.1007/s11325-019-01802-w. Epub 2019 Feb 23.
citation: Hodges E, Marcus CL, Kim JY, Xanthopoulos M, Shults J, Giordani B, Beebe DW, Rosen CL, Chervin RD, Mitchell RB, Katz ES, Gozal D, Redline S, Elden L, Arens R, Moore R, Taylor HG, Radcliffe J, Thomas NH. Depressive symptomatology in school-aged children with obstructive sleep apnea syndrome: incidence, demographic factors, and changes following a randomized controlled trial of adenotonsillectomy. Sleep. 2018 Dec 1;41(12):zsy180. doi: 10.1093/sleep/zsy180.
citation: Liu X, Immanuel S, Kennedy D, Martin J, Pamula Y, Baumert M. Effect of adenotonsillectomy for childhood obstructive sleep apnea on nocturnal heart rate patterns. Sleep. 2018 Nov 1;41(11):zsy171. doi: 10.1093/sleep/zsy171.
citation: Thomas NH, Xanthopoulos MS, Kim JY, Shults J, Escobar E, Giordani B, Hodges E, Chervin RD, Paruthi S, Rosen CL, Taylor GH, Arens R, Katz ES, Beebe DW, Redline S, Radcliffe J, Marcus CL. Effects of Adenotonsillectomy on Parent-Reported Behavior in Children With Obstructive Sleep Apnea. Sleep. 2017 Apr 1;40(4):zsx018. doi: 10.1093/sleep/zsx018.
citation: Liu X, Immanuel S, Pamula Y, Kennedy D, Martin J, Baumert M. Adenotonsillectomy for childhood obstructive sleep apnoea reduces thoraco-abdominal asynchrony but spontaneous apnoea-hypopnoea index normalisation does not. Eur Respir J. 2017 Jan 25;49(1):1601177. doi: 10.1183/13993003.01177-2016. Print 2017 Jan.
citation: Wang R, Dong Y, Weng J, Kontos EZ, Chervin RD, Rosen CL, Marcus CL, Redline S. Associations among Neighborhood, Race, and Sleep Apnea Severity in Children. A Six-City Analysis. Ann Am Thorac Soc. 2017 Jan;14(1):76-84. doi: 10.1513/AnnalsATS.201609-662OC.
citation: Paruthi S, Buchanan P, Weng J, Chervin RD, Mitchell RB, Dore-Stites D, Sadhwani A, Katz ES, Bent J, Rosen CL, Redline S, Marcus CL. Effect of Adenotonsillectomy on Parent-Reported Sleepiness in Children with Obstructive Sleep Apnea. Sleep. 2016 Nov 1;39(11):2005-2012. doi: 10.5665/sleep.6232.
citation: Taylor HG, Bowen SR, Beebe DW, Hodges E, Amin R, Arens R, Chervin RD, Garetz SL, Katz ES, Moore RH, Morales KH, Muzumdar H, Paruthi S, Rosen CL, Sadhwani A, Thomas NH, Ware J, Marcus CL, Ellenberg SS, Redline S, Giordani B. Cognitive Effects of Adenotonsillectomy for Obstructive Sleep Apnea. Pediatrics. 2016 Aug;138(2):e20154458. doi: 10.1542/peds.2015-4458.
citation: Paruthi S, Rosen CL, Wang R, Weng J, Marcus CL, Chervin RD, Stanley JJ, Katz ES, Amin R, Redline S. End-Tidal Carbon Dioxide Measurement during Pediatric Polysomnography: Signal Quality, Association with Apnea Severity, and Prediction of Neurobehavioral Outcomes. Sleep. 2015 Nov 1;38(11):1719-26. doi: 10.5665/sleep.5150.
citation: Chervin RD, Ellenberg SS, Hou X, Marcus CL, Garetz SL, Katz ES, Hodges EK, Mitchell RB, Jones DT, Arens R, Amin R, Redline S, Rosen CL; Childhood Adenotonsillectomy Trial. Prognosis for Spontaneous Resolution of OSA in Children. Chest. 2015 Nov;148(5):1204-1213. doi: 10.1378/chest.14-2873.
citation: Quante M, Wang R, Weng J, Rosen CL, Amin R, Garetz SL, Katz E, Paruthi S, Arens R, Muzumdar H, Marcus CL, Ellenberg S, Redline S; Childhood Adenotonsillectomy Trial (CHAT). The Effect of Adenotonsillectomy for Childhood Sleep Apnea on Cardiometabolic Measures. Sleep. 2015 Sep 1;38(9):1395-403. doi: 10.5665/sleep.4976.
citation: Garetz SL, Mitchell RB, Parker PD, Moore RH, Rosen CL, Giordani B, Muzumdar H, Paruthi S, Elden L, Willging P, Beebe DW, Marcus CL, Chervin RD, Redline S. Quality of life and obstructive sleep apnea symptoms after pediatric adenotonsillectomy. Pediatrics. 2015 Feb;135(2):e477-86. doi: 10.1542/peds.2014-0620. Epub 2015 Jan 19.
citation: Mitchell RB, Garetz S, Moore RH, Rosen CL, Marcus CL, Katz ES, Arens R, Chervin RD, Paruthi S, Amin R, Elden L, Ellenberg SS, Redline S. The use of clinical parameters to predict obstructive sleep apnea syndrome severity in children: the Childhood Adenotonsillectomy (CHAT) study randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2015 Feb;141(2):130-6. doi: 10.1001/jamaoto.2014.3049.
citation: Katz ES, Moore RH, Rosen CL, Mitchell RB, Amin R, Arens R, Muzumdar H, Chervin RD, Marcus CL, Paruthi S, Willging P, Redline S. Growth after adenotonsillectomy for obstructive sleep apnea: an RCT. Pediatrics. 2014 Aug;134(2):282-9. doi: 10.1542/peds.2014-0591.
citation: Weinstock TG, Rosen CL, Marcus CL, Garetz S, Mitchell RB, Amin R, Paruthi S, Katz E, Arens R, Weng J, Ross K, Chervin RD, Ellenberg S, Wang R, Redline S. Predictors of obstructive sleep apnea severity in adenotonsillectomy candidates. Sleep. 2014 Feb 1;37(2):261-9. doi: 10.5665/sleep.3394.
citation: Marcus CL, Moore RH, Rosen CL, Giordani B, Garetz SL, Taylor HG, Mitchell RB, Amin R, Katz ES, Arens R, Paruthi S, Muzumdar H, Gozal D, Thomas NH, Ware J, Beebe D, Snyder K, Elden L, Sprecher RC, Willging P, Jones D, Bent JP, Hoban T, Chervin RD, Ellenberg SS, Redline S; Childhood Adenotonsillectomy Trial (CHAT). A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med. 2013 Jun 20;368(25):2366-76. doi: 10.1056/NEJMoa1215881. Epub 2013 May 21.