Clinical trial NCT01161420: Stimulation Therapy for Apnea Reduction (Www.theSTARtrial.Com)
Official title: Effects of the Inspire Implantable Nerve Stimulation System on Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obstructive Sleep Apnea
Keywords: tongue
surgery
neurostimulation
hypoglossal nerve
upper airway stimulation
Lead sponsor: Inspire Medical Systems, Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-13
Enrollment: 929
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Apnea Hypopnea Index
timeFrame: 12 months
measure: Oxygen Desaturation Index
timeFrame: 12 months
measure: Safety
timeFrame: 12 months
Secondary outcomes:
measure: AHI for the Randomized Controlled Therapy (RCT) Withdrawal Study
timeFrame: 12 Months
measure: Modified Intent to Treat - AHI Responder Rate for All Implanted Subjects
timeFrame: 12 months
measure: Change in FOSQ From Baseline to 12 Months
timeFrame: Baseline and 12 months
measure: Change Epworth Sleepiness Scale (ESS) From Baseline to 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Sleep Time at SaO2 < 90%
timeFrame: 12 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: California Sleep Institute
state: California
city: Saint Petersburg
country: United States
facility: Clinical Research Group of St. Petersburg, Inc.
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Advanced ENT
state: Georgia
city: Detroit
country: United States
facility: Wayne State University / Detroit Medical Center
state: Michigan
city: Portage
country: United States
facility: Borgess Research Institute
state: Michigan
city: Maple Grove
country: United States
facility: North Memorial Medical Center
state: Minnesota
city: Saint Cloud
country: United States
facility: St. Cloud ENT
state: Minnesota
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals / Case Western Reserve
state: Ohio
city: Oakland
country: United States
facility: University of Pittsburgh Medical Center; Montefiore
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Sleep Medicine Associates of Texas
state: Texas
city: Seattle
country: United States
facility: Swedish Health Services
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Memeorial Hospital
state: Wisconsin
city: Antwerp
country: Belgium
facility: Deparment of Pulmonology Head and Neck Surgery, Universitair Ziekenhuis Antwerpen
city: Bordeaux
country: France
facility: Central Hospital University of Bordeaux
city: Paris
country: France
facility: Hospital Foch
city: Solingen
country: Germany
facility: Krankenhaus Bethanien Solingen
state: DE
city: Koln
country: Germany
facility: St. Franziskus Hospital
city: Mannheim
country: Germany
facility: Universitäts-HNO-Klinik Mannheim
city: Amsterdam
country: Netherlands
facility: St. Lucas Andreas Ziekenhuis
Study officials:
affiliation: Inspire Medical Systems, Inc.
name: Quan Ni, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Johnson MD, Dweiri YM, Cornelius J, Strohl KP, Steffen A, Suurna M, Soose RJ, Coleman M, Rondoni J, Durand DM, Ni Q. Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea. Sleep. 2021 Apr 27;44(44 Suppl 1):S11-S19. doi: 10.1093/sleep/zsaa269.
citation: Yu JL, Younes M. Relation between arousability and outcome of upper airway stimulation in the Stimulation for Apnea Reduction (STAR) Trial. J Clin Sleep Med. 2021 Apr 1;17(4):797-801. doi: 10.5664/jcsm.9050.
citation: Op de Beeck S, Wellman A, Dieltjens M, Strohl KP, Willemen M, Van de Heyning PH, Verbraecken JA, Vanderveken OM, Sands SA; STAR Trial Investigators. Endotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2021 Mar 15;203(6):746-755. doi: 10.1164/rccm.202006-2176OC.
citation: Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, Hanson RD, Padhya TA, Steward DL, Gillespie MB, Woodson BT, Van de Heyning PH, Goetting MG, Vanderveken OM, Feldman N, Knaack L, Strohl KP; STAR Trial Group. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014 Jan 9;370(2):139-49. doi: 10.1056/NEJMoa1308659.