Bi-lateral HGN Therapy in Real-World Patients -Post Approval Research Investigation (BREATHE)

The objective of the BREATHE study is to demonstrate the continued safety and effectiveness of the Genio® System in treating subjects diagnosed with moderate to severe obstructive sleep apnea (OSA) who are intolerant to or failed/refused PAP treatments.

Study Overview

• Status: Not yet recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: This is a single arm study, all consented and eligible subjects will be implanted with the Genio® System 2.1

Detailed Description

BREATHE is a multicenter, prospective, single-arm, post-approval study. Following a baseline visit and implantation of the Genio® System 2.1, subjects will be asked to return for a therapy activation visit at approximately 8 weeks post-implant surgery.

The subject will have follow-up visits at 6 months, 9 months, 12 months and every 6-months thereafter up to 5 years post-implant surgery. Additional visits (for device titration or other reasons) are per standard of care and at the Investigator's discretion. Endpoints will be assessed at 12, 24, 36, 48 and 60 months.

• Study Type: Observational
• Enrollment (Estimated): 229

Contacts and Locations

• Study Contact: Name: Lorin Pétré; Phone Number: +1 (908) 263-0228; Email: clinical.studies@nyxoah.com
• Study Contact Backup: Name: Alicia Castonguay; Email: clinical.studies@nyxoah.com

Study Locations

• United States
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Nyxoah, Inc
      • Contact: Alicia Castonguay; Email: clinical.studies@nyxoah.com
      • Contact: Lorin Petre; Phone Number: 908-263-0228; Email: clinical.studies@nyxoah.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects diagnosed with moderate to severe obstructive sleep apnea (OSA) who are intolerant to or failed/refused PAP treatments.

Description

Inclusion Criteria:

1. Have an apnea-hypopnea index (AHI) greater than or equal to 15 and less than or equal to 65, measured on a full-night PSG performed no earlier than 2 years prior to enrollment (AHI4 and ODI4 available).
2. Be adults 22 years of age and older.
3. Have been confirmed to have failed, not tolerated, or be ineligible to be treated with current standard of care treatments for moderate to severe OSA.
4. Have pursued insurance pre-authorization for Genio® Therapy, recognizing that pre-authorization does not ensure payment, or demonstrate willingness to assume any out-of-pocket costs. The sponsor will not be responsible for treatment-related charges.
5. Agree to participate in the study and voluntarily sign and date an informed consent form.
6. Be willing and capable of complying with all study requirements, including specific lifestyle considerations, performing all follow-up visits, evaluation procedures and questionnaires for the whole duration of the trial.
7. Have a result of a Drug- Induced Sleep Endoscopy (DISE), no earlier than 2 years prior to enrollment.

Exclusion Criteria:

1. Combined central and mixed apnea-hypopnea index (AHI) greater than or equal to 25% of the total AHI.
2. Any functional or structural problem, medical illness or condition that would prevent or interfere with implantation, activation or continued use of the Genio® Therapy.
3. Have an implantable device which may be susceptible to unintended interaction with the Genio® System 2.1.
4. Women who are pregnant, planning to become pregnant or breastfeeding.
5. Any condition or procedure that has compromised neurological control of the upper airway.

6. Be part of the populations for which the safety and effectiveness of the Genio® System 2.1 has not been fully assessed:

   1. Patients below 22 or above 75 years of age.
   2. Patients with a Body Mass Index (BMI) above 32 kg/m2.
   3. Patients with an Apnea Hypopnea Index (AHI) below 15 or over 65 events/hr.
   4. Patients with Complete Concentric Collapse (CCC) at the soft palate level.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Genio System 2.1; This is a single-arm study. All consented and eligible subjects will be implanted with the Genio 2.1 System.	Device: This is a single arm study, all consented and eligible subjects will be implanted with the Genio® System 2.1; Genio® System 2.1; Other Names: Genio Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Apnea Hypopnea Index (AHI4%)	Percentage of responders at 12 months based on AHI4	12 months
Change in Oxyhemoglobin Desaturation Index (ODI4%)	Percentage of responders at 12 months based on ODI4	12 months
Device related SAEs	Incidence of device-related Serious Adverse Events at 12 months post-surgery	12 months
Device-related and procedure-related SAEs	Incidence of device-related and procedure-related SAEs at 12 months post-surgery	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in AHI4	Mean change in AHI4 from screening to 12, 24, 36, 48, and 60 months post-surgery.	Baseline to 5 years
Mean change in ODI4	Mean change in ODI4 from screening to 12, 24, 36, 48, and 60 months post-surgery.	Baseline to 5 years
% responders AHI4	Percentage of responders at 24, 36, 48, and 60 months based on AHI4 according to "Sher criteria".	2 years through 5 years
% responders ODI4	Percentage of responders at 24, 36, 48 and 60 months based on ODI4	2 years through 5 years
Subject Satisfaction	Subject reported satisfaction with therapy (measured via bespoke questionnaire) measured at 12, 24, 36, 48, and 60 months post-surgery	1 year through 5 years
Improvement in ESS	Improvement in OSA-related symptoms (measured via Epworth Sleepiness Scale (ESS) questionnaire) measured at 12, 24, 36, 48, and 60 months post-surgery	1 year through 5 years
Change in health status	Subject reported impression of change in health status (measured via Patient Global Impression of Change (PGIC) questionnaire) at 12, 24, 36, 48, and 60 months post-surgery.	1 year through 5 years
Clinician impression of change in Subject's health status	Clinician impression of change in Subject's health status (measured via Clinician Global Impression of Change (CGIC) questionnaire) at 12, 24, 36, 48, and 60 months post-surgery.	1 year through 5 years
Device-related Serious Adverse Events	Incidence of device-related Serious Adverse Events, as reported by Investigator and adjudicated by the CEC, at 24, 36, 48, and 60 months post-surgery.	2 years through 5 years

Collaborators and Investigators

• Sponsor: Nyxoah Inc.

Publications and helpful links

General Publications

• Woodson BT, Kent DT, Huntley C, Hancock MK, Van Daele DJ, Boon MS, Huntley TC, Mickelson S, Gillespie MB, Suurna MV, Kacker A, Roy A, MacKay S, Withrow KP, Dedhia RC, Huyett P, Heiser C, Nicola SD, Makori F, Vanderveken OM, Padyha TA, Magalang UJ, Chio E, Kezirian EJ, Lewis R. Bilateral hypoglossal nerve stimulation for obstructive sleep apnea: a nonrandomized clinical trial. J Clin Sleep Med. 2025 Nov 1;21(11):1883-1891. doi: 10.5664/jcsm.11822.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2032

Study Registration Dates

• First Submitted: December 29, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: OSA; obstructive sleep apnea; Hypoglossal Nerve Stimulation; Genio
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: CL-BREATHE-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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