Stimulation Therapy for Apnea Reduction (Www.theSTARtrial.Com)

Obstructive Sleep Apnea Clinical Trial

— STAR  

Official title:

Effects of the Inspire Implantable Nerve Stimulation System on Obstructive Sleep Apnea

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01161420
• Other study ID #: Inspire 4
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 9, 2010
• Last updated: March 15, 2016
• Start date: July 2010
• Est. completion date: March 2017

Study information

• Verified date: March 2016
• Source: Inspire Medical Systems, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsUnited States: Food and Drug AdministrationGermany: German Institute of Medical Documentation and InformationNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial is to demonstrate long-term safety and efficacy of the Inspire system. The Inspire Upper Airway Stimulation (UAS) therapy is intended to treat moderate-to-severe obstructive sleep apnea by improving airway patency through stimulation of the hypoglossal nerve. Study objectives include demonstrating that the Inspire system improves key indices of sleep apnea in a pre-specified percentage of patients.

Description:

The STAR trial is a multicenter, prospective trial that includes a randomized controlled therapy withdrawal study. The primary and secondary endpoint data were collected during an in-laboratory sleep study 12 months after the device implant and were compared against the baseline sleep studies. Following the 12-month visit, 46 consecutive responding subjects were randomized 1:1 to either a therapy maintenance group (ON group) or a therapy withdrawal group (OFF group). A subsequent sleep study of the two randomized groups was conducted and results were compared between the two groups. In addition, quality of life questionnaires were administered at baseline and at the 12-month visit to further assess the effectiveness of Inspire therapy.

The STAR trial was conducted at 15 clinical sites in the United States and 7 in Europe. Of the 126 implanted subjects in the STAR trial, 87 or 69% were implanted in the United States. The remaining 39 subjects or 31% were implanted in Europe.

The STAR trial subjects were evaluated prior to implant to ensure the following: 1) that their pre-implant AHI (as scored during an in-laboratory sleep study prior to implant) was between 20 and 50 events per hour, 2) that any AHI contribution from central or mixed sleep apnea was less than 25%, 3) that subjects did not have primarily lateral OSA (defined as limited sleep apnea when lying on their side), and 4) that the subjects did not have a complete concentric collapse at the level of the soft palate while observed during a drug-induced sleep endoscopy (DISE).

After successful pre-implant screening, the subjects were implanted with the Inspire system. The subjects were allowed to recover for 1 month following surgery, at which time a second in-laboratory sleep study was conducted without activating the Inspire device. The results of this 1-month sleep study were averaged with the results of the pre-implant sleep study, and the average is defined as the subject's baseline.

The Inspire device is programmable in order to optimize a subject's response to therapy. The initial device settings are programmed in an office setting. Additional adjustments are made during an overnight sleep study whereby real time review of the polysomnogram (PSG) is available to aid in device setting adjustments during the 2 and 6-month visit.

At the 12-month in-laboratory sleep study, no device adjustments were allowed as this sleep study was the primary endpoint sleep study. Furthermore, no device adjustments were allowed at the 13-month sleep study which was the randomized controlled therapy withdrawal sleep studies.

Blinding was not possible during the study since the stimulation therapy evokes a physiological response in the subjects. However, the primary endpoints were based on the objective measures of AHI and oxygen desaturation index (ODI) which were collected during an overnight sleep study using PSG. The sleep studies were all scored by an independent core lab in order to minimize assessment bias. Furthermore, the sleep study results, as well as all other clinical results, were 100% source data verified by the Inspire clinical monitoring team.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 929
• Est. completion date: March 2017
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 22 Years and older

Eligibility

Inclusion Criteria:

• Likely suffer moderate-to-severe OSA based on history and physical

• Have failed or have not tolerated CPAP treatment

• Willing and capable of providing informed consent

• Willing and capable to have stimulation hardware permanently implanted, and to use the patient programmer to activate the stimulation

• Willing and capable to return for all follow-up visits and sleep studies, including the evaluation procedures and filling out the questionnaires

Exclusion Criteria:

• Body Mass Index limits

• Surgical resection or radiation therapy for cancer or congenital malformations in the larynx, tongue, or throat

• Significant co-morbidities making the patient unable or inappropriate to participate in the trial

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Device:
• Inspire Upper Airway Stimulation System
Inspire Upper Airway Stimulation System, is a permanent, implantable therapy device, which consists of three implantable components: IPG, stimulation lead, and a sensing lead. In additional the patient receives a remote to activate the therapy.

Locations

Country	Name	City	State
Belgium	Deparment of Pulmonology Head and Neck Surgery, Universitair Ziekenhuis Antwerpen	Antwerp
France	Central Hospital University of Bordeaux	Bordeaux
France	Hospital Foch	Paris
Germany	St. Franziskus Hospital	Koln
Germany	Universitäts-HNO-Klinik Mannheim	Mannheim
Germany	Krankenhaus Bethanien Solingen	Solingen	DE
Netherlands	St. Lucas Andreas Ziekenhuis	Amsterdam
United States	Advanced ENT	Atlanta	Georgia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University Hospitals / Case Western Reserve	Cleveland	Ohio
United States	Sleep Medicine Associates of Texas	Dallas	Texas
United States	Wayne State University / Detroit Medical Center	Detroit	Michigan
United States	North Memorial Medical Center	Maple Grove	Minnesota
United States	Froedtert Memeorial Hospital	Milwaukee	Wisconsin
United States	University of Pittsburgh Medical Center; Montefiore	Oakland	Pennsylvania
United States	California Sleep Institute	Palo Alto	California
United States	Borgess Research Institute	Portage	Michigan
United States	Swedish Health Services	Seattle	Washington
United States	Clinical Research Group of St. Petersburg, Inc.	St Petersburg	Florida
United States	St. Cloud ENT	St. Cloud	Minnesota
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Inspire Medical Systems, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apnea Hypopnea Index	Demonstrate at least a 50% responder rate at the 12-month follow-up visit. An Inspire therapy AHI responder was defined as a subject who experienced at least a 50% reduction in AHI from baseline and had an AHI of less than 20 at the 12-month follow-up.	12 months	No
Primary	Oxygen Desaturation Index	Demonstrate at least a 50% responder rate at the 12-month follow-up visit. An Inspire therapy ODI responder was defines as a subject who experienced at least a 25% reduction in ODI from baseline.	12 months	No
Primary	Safety	The primary safety objective of this pivotal trial was to evaluate safety via a description of all reported adverse events. Per the IDE-approved protocol, no formal statistical hypothesis was tested as part of the safety assessment.	12 months	Yes
Secondary	AHI for the Randomized Controlled Therapy (RCT) Withdrawal Study	The AHI difference between the 12-month PSG study and the 13-Month PSG study in the therapy maintenance group will be compared to the AHI difference in the therapy withdrawal group. The objective was to demonstrate that AHI increase in the therapy withdrawal group (therapy=OFF) is greater than any AHI change in the active therapy group (therapy=ON). AHI is the number of apneas or hypopneas recorded during a sleep study per hour of sleep; this is calculated by dividing the number of AHI events by the number of hours of sleep.	12 Months	No
Secondary	Modified Intent to Treat - AHI Responder Rate for All Implanted Subjects	The intent-to-treat (ITT) analysis for the primary endpoint included all patients who underwent an implant. A modified ITT analysis was conducted to include the subjects who did not completed the 12-month follow-up sleep study also. The ITT analysis was to calculate the AHI responder rate based on the subjects included in the analysis as described below. An Inspire therapy AHI responder was defined as a subject who experienced at least a 50% reduction in AHI from baseline and had an AHI of less than 20 at their last visit.; The following subjects were included: All implanted subjects who had AHI data collected at both baseline and 12-months follow-up.; All implanted subjects who had baseline data but no 12-month data, and had their last data values carried forward, provide they had a least 6-month AHI data.; Any implanted subject who did not have 12-month data available due to therapy failure (e.g., study withdrawal will be included in the analsys as a treatment failure.	12 months	No
Secondary	Change in FOSQ From Baseline to 12 Months	The Functional Outcomes Sleep Questionnaire (FOSQ) is a validated instrument that assesses the effect of a subject's daytime sleepiness on activities of ordinary living. It is a quality of life measure that is commonly used in the clinical evaluation and management of OSA. This self-administered instrument consists of 30 questions divided into 5 domains: activity level, vigilance, intimacy, general productivity and social outcome. Scores range from 5 to 20, with higher scores indicating greater functioning. Change in FOSQ was calculated by subtracting the baseline score from the 12-month score.	Baseline and 12 months	No
Secondary	Change Epworth Sleepiness Scale (ESS) From Baseline to 12 Months	The Epworth Sleepiness Scale (ESS) is a validated instrument that rates a subject's daytime sleepiness. Like the FOSQ, it is a quality of life measure that is commonly used in clinical evaluation and management of OSA. Scores range from 0 to 24, with lower scores indicating greater functioning. An ESS score of less than 10 is considered to be the cutpoint for normal subjective sleepiness.	Baseline and 12 months	No
Secondary	Percentage Sleep Time at SaO2 < 90%	The percentage of time spent with oxygen saturation below 90% has been an increasingly utilized surrogate for morbidity risk in sleep apnea populations.; The SaO2 secondary endpoint in this study was determined by the time below an SaO2 level of 90% during the 12-month PSG study compared to that at baseline (average of screening and 1-month PSG studies). The objective was to demonstrate a decrease in the percentage of sleep time with an SaO2 level below 90% at 12 months.	12 months	No

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