RCT of the Effect of Uvulopalatopharyngoplasty Compared to Expectancy in Patients With Obstructive Sleep Apnea (SKUP3)

Hypothesis:Pharyngeal surgery (UPPP) reduces significantly the nightly respiratory breathing pauses (apnoeas-hypopnoeas) and improves the daytime symptoms compared to expectancy for 6 months in patients with OSAS.

Background: Obstructive sleep apnea syndrome (OSAS) is associated with an increased risk of poor sleep quality, excessive daytime sleepiness and prolonged reaction time, which can elevate the risk for traffic accidents. Increased morbidity and three to four times increased mortality in these patients are well documented, mainly in the cardiovascular field. Pharyngeal surgery, i.e. uvulopalatopharyngoplasty (UPPP) opens up the airway and was the predominant treatment for OSAS worldwide before continuous positive airway pressure (CPAP) devices became widely available in the 1990s. Since then, the main treatment for OSAS has been CPAP, but an increasing number of patients are also treated with mandibular retaining device (MRD). UPPP as treatment for OSAS has been performed for 30 years. The evidence-grade for the efficacy has so far been very low, and the side-effects and complication rate has raised the question whether there is a place for surgical treatment of OSAS. However, the compliance for CPAP and dental devices are quite low (50-60%), leaving a lot of patients untreated if surgery is not offered. RCT UPPP is still missing and called for.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea Syndrome
• Intervention / Treatment: Procedure: Uvulopalatopharyngoplasty

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 141 86
    • Orl dep, Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

ApnéHypopnéIndex, AHI >14,9 Daytime sleepiness w Epworth sleepiness scale, ESS> 7 Sleepy during daytime 3-5 times per week or more BodyMassIndex, BMI < 36,0 Friedman staging system of tonsil size and tongue: i and II Patients w Friedman stage I and BMI < 30,0 could be directly included if patient positive and no contra-indications for surgery. All others should be failure of CPAP and MRD before inclusion.

Exclusion Criteria:

Other OSAS treatment during study, i.e., patient is clinically severely deteriorated.

Negative to surgery Night-shift worker Friedman stage III or IV Morbid obesity BMI >35,9 Severe psychological or neurological disease ASA class >3 Severe lung- or heart disease (not applicable for hypertension, nor stroke or MI more than after 2 years).

Insufficient knowledge in Swedish language (important for filling in questionnaires) Dangerous in traffic while driving Severe nasal congestion (can be included after successful treatment) Previous tonsillectomy

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Uvulopalatopharyngoplasty; One arm is Uvulopalatopharyngoplasty(intervention group of 32 patients), one arm is expectancy (control group of 33 patients). After six months the controls have delayed surgery and then both groups are followed for two years	Procedure: Uvulopalatopharyngoplasty; Uvulopalatopharyngoplasty: Resection of the soft palate 3 mm and tonsillectomy, amputation of the uvula to approx 1 cm, single sutures of the posterior pillar to the anterior pillar and of the soft palate.
Active Comparator: Control; After six months the controls have delayed surgery then are followed for 2 year	Procedure: Uvulopalatopharyngoplasty; Uvulopalatopharyngoplasty: Resection of the soft palate 3 mm and tonsillectomy, amputation of the uvula to approx 1 cm, single sutures of the posterior pillar to the anterior pillar and of the soft palate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in apnea-hypopnea index	Apnea-hypopnea index (AHI) is the number of apneas or hypopneas per sleep hour. Polysomnography (PSG) is the Golden standard to use when measuring the AHI. PSG is the method we are using	6 months and 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Epworth sleepiness scale	Epworth sleepiness scale is a validated questionnaire. It consists of eight questions concerning the patients´ ability to fall asleep in different situations. The total sum is 24.	6 months and 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Oxygen desaturation index	Oxygen desaturation index (ODI) is the number of oxygen desaturations of 3 % or more per sleep hour.	6 months and 2 years
changes in blood samples	Hb, LPK, CRP, cortisol, TSH, T4, ASAT, ALAT, ALP, γ-GT, CDT, Leptin/ghrelin, fB-Glucose, f-insulin, HDL, LDL, Cholesterol, Triglycerides, TNF-α, IL-1, IL-6	6 months 2 years
changes in score of SF 36 quality of life questionnaire	QoL SF 36 validated questionnaire	6 months and 2 years
changes in blood pressure	systolic and diastolic morning pressure from arm	6 months and 2 years
changes in vigilance	modified Osler test	6 months and 2 years
number of patients with serious complications from surgery		6 months
number of patients with side-effects from surgery	answers from a local questionnaire regaring pharyngeal side-effects	6 months and 2 years
Changes in score of FOSQ questionnaire	Validated questionnaire designed for patients with obstructive sleep apnea syndrome	6 months and 2 years
identifying success factors for outcome of surgical intervention	Correlate for example tonsil size and tongue position (stageing system) with changes in AHI	6 months 2 years
changes in arousal index	Polysomnographic results	6 months and 2 years
changes in lowest oxygen saturation during sleep	Polysomnographic results	6 months 2 years
changes in ODI during REM sleep	Polysomnographic results	6 months 2 years
changes in ODI in supine position	Polysomnographic results	6 months 2 years
changes in time in supine position	Polysomnographic results	6 months and 2 years
changes in Body Mass Index		6 months and 2 years
changes in RERA index	Polysomnographic results, RERA are the respiratory effort related arousals during sleep	6 months and 2 years
changes in mean length apneas and hypopneas	Polysomnographic results	6 months and 2 years
changes in AHI supine position	Polysomnographic results	6 months 2 years
changes in AHI in REM	Polysomnographic results	6 months and 2 years
changes in total sleep time	Polysomnograåhic results	6 months and 2 years
changes in RDI	Polysomnographic results; RDI is the sum of AHI and RERA index	6 months and 2 years

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Danielle K Friberg, MD, PhD, Associate professor, Karolinska University Hospital, Karolinska Institutet

Publications and helpful links

General Publications

• Joar S, Danielle F, Johan B, Arne L, Roberta N, Nanna B. Sleep Quality After Modified Uvulopalatopharyngoplasty: Results From the SKUP3 Randomized Controlled Trial. Sleep. 2018 Jan 1;41(1). doi: 10.1093/sleep/zsx180. Erratum In: Sleep. 2018 Nov 1;41(11):
• Fehrm J, Friberg D, Bring J, Browaldh N. Blood pressure after modified uvulopalatopharyngoplasty: results from the SKUP3 randomized controlled trial. Sleep Med. 2017 Jun;34:156-161. doi: 10.1016/j.sleep.2017.02.030. Epub 2017 Apr 4.
• Browaldh N, Bring J, Friberg D. SKUP(3) RCT; continuous study: Changes in sleepiness and quality of life after modified UPPP. Laryngoscope. 2016 Jun;126(6):1484-91. doi: 10.1002/lary.25642. Epub 2015 Sep 25.
• Browaldh N, Nerfeldt P, Lysdahl M, Bring J, Friberg D. SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea. Thorax. 2013 Sep;68(9):846-53. doi: 10.1136/thoraxjnl-2012-202610. Epub 2013 May 5.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: August 6, 2012
• First Submitted That Met QC Criteria: August 7, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Estimate): December 15, 2014
• Last Update Submitted That Met QC Criteria: December 12, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: 2007/449-31/3, Ö 21-2007 (Other Identifier: Ethic Committee, Karolinska Institutet, Stockholm, Sweden)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No