Reboxetine for Sleep Apnoea After ENT Surgery

NCT05978505 | Recruiting Phase 2

• 1 other identifier: 2023/HRE00060
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study will establish the feasibility of a larger trial to investigate whether reboxetine, a medication used to treat depression, can reduce the severity of obstructive sleep apnea (OSA) including increased blood oxygenation in post-surgical OSA patients where positive airway pressure (CPAP) therapy is either frequently poorly tolerated or not an option immediately post surgery. In this randomized, placebo-controlled, double-blind study, participants will use at-home sleep monitoring equipment before and after surgery plus measures of oxygenation. They will be prescribed either reboxetine or a placebo for seven days after surgery and complete questionnaires at the beginning and end of the study.

Conditions

Sleep Apnea, Obstructive

Keywords

sleep apnea, obstructive; upper airway surgery; ENT surgery; reboxetine; noradrenaline reuptake inhibitor; randomised; feasibility; placebo; double-blind

Outcome Measures

Primary Outcomes (2)

• Treatment protocol adherence

  The percentage of total doses of the study drug (reboxetine or placebo) that were taken versus prescribed (assessed via pill counts) for this feasibility study.

  7 days

• Data capture efficiency

  The percentage of successful data collection nights versus missed nights of at-home oximetry for this feasibility study.

  14 days

Secondary Outcomes (11)

• Oxygen desaturation index (ODI)

  14 days

• nadir SpO2

  14 days

• Time spent below 90% SpO2

  14 days

• mean SpO2

  14 days

• Sleep duration

  14 days

Other Outcomes (1)

• Reboxetine-related side effects

  14 days

Study Arms (2)

Reboxetine

EXPERIMENTAL

7-day course of 4mg reboxetine, taken nightly before bed time. Reboxetine will be taken for 7-nights post-surgery.

Drug: Reboxetine 4 MG Oral Tablet

Placebo

PLACEBO COMPARATOR

Placebo sugar pill in the form of one capsule, taken before bedtime. Dosage is taken for 7 nights post-surgery.

Drug: Placebo

Interventions

Reboxetine 4 MG Oral Tablet DRUG

7 nightly doses (4mg) to commence after surgery.

Also known as: Edronax

Reboxetine

Placebo DRUG

7 nightly doses to commence after surgery.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Undergoing elective upper airway surgery
• History of obstructive sleep apnoea (OSA)

You may not qualify if:

• Clinically significant cardiac disease (e.g., arrhythmia, coronary artery disease, or cardiac failure)
• History of clinically significant urinary retention, bladder outlet obstruction, or benign prostatic hyperplasia
• Poorly controlled hypertension
• Epilepsy
• History of schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-V or International Classification of Disease 10th edition criteria
• History of attempted suicide or suicidal ideation within 1 year prior to screening, or current suicidal ideation
• Narrow angle glaucoma

Sponsors & Collaborators

• Flinders University: lead
• Flinders Medical Centre: collaborator

Study Sites (1)

Flinders, Private and Public Hospitals and Flinders University

Bedford Park, South Australia, 5042, Australia

RECRUITING

Related Publications (12)

• Opperer M, Cozowicz C, Bugada D, Mokhlesi B, Kaw R, Auckley D, Chung F, Memtsoudis SG. Does Obstructive Sleep Apnea Influence Perioperative Outcome? A Qualitative Systematic Review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing. Anesth Analg. 2016 May;122(5):1321-34. doi: 10.1213/ANE.0000000000001178.

  PMID: 27101493 BACKGROUND

• Chan MTV, Wang CY, Seet E, Tam S, Lai HY, Chew EFF, Wu WKK, Cheng BCP, Lam CKM, Short TG, Hui DSC, Chung F; Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) Study Investigators. Association of Unrecognized Obstructive Sleep Apnea With Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery. JAMA. 2019 May 14;321(18):1788-1798. doi: 10.1001/jama.2019.4783.

  PMID: 31087023 BACKGROUND

• Khanna AK, Bergese SD, Jungquist CR, Morimatsu H, Uezono S, Lee S, Ti LK, Urman RD, McIntyre R Jr, Tornero C, Dahan A, Saager L, Weingarten TN, Wittmann M, Auckley D, Brazzi L, Le Guen M, Soto R, Schramm F, Ayad S, Kaw R, Di Stefano P, Sessler DI, Uribe A, Moll V, Dempsey SJ, Buhre W, Overdyk FJ; PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) Group Collaborators. Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial. Anesth Analg. 2020 Oct;131(4):1012-1024. doi: 10.1213/ANE.0000000000004788.

  PMID: 32925318 BACKGROUND

• Altree TJ, Eckert DJ. Obstructive sleep apnea endotypes and their postoperative relevance. Int Anesthesiol Clin. 2022 Apr 1;60(2):1-7. doi: 10.1097/AIA.0000000000000357. No abstract available.

  PMID: 35125480 BACKGROUND

• Chung F, Liao P, Yegneswaran B, Shapiro CM, Kang W. Postoperative changes in sleep-disordered breathing and sleep architecture in patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):287-98. doi: 10.1097/ALN.0000000000000040.

  PMID: 24158049 BACKGROUND

• Chung F, Memtsoudis SG, Ramachandran SK, Nagappa M, Opperer M, Cozowicz C, Patrawala S, Lam D, Kumar A, Joshi GP, Fleetham J, Ayas N, Collop N, Doufas AG, Eikermann M, Englesakis M, Gali B, Gay P, Hernandez AV, Kaw R, Kezirian EJ, Malhotra A, Mokhlesi B, Parthasarathy S, Stierer T, Wappler F, Hillman DR, Auckley D. Society of Anesthesia and Sleep Medicine Guidelines on Preoperative Screening and Assessment of Adult Patients With Obstructive Sleep Apnea. Anesth Analg. 2016 Aug;123(2):452-73. doi: 10.1213/ANE.0000000000001416.

  PMID: 27442772 BACKGROUND

• Liao P, Luo Q, Elsaid H, Kang W, Shapiro CM, Chung F. Perioperative auto-titrated continuous positive airway pressure treatment in surgical patients with obstructive sleep apnea: a randomized controlled trial. Anesthesiology. 2013 Oct;119(4):837-47. doi: 10.1097/ALN.0b013e318297d89a.

  PMID: 24195872 BACKGROUND

• Altree TJ, Chung F, Chan MTV, Eckert DJ. Vulnerability to Postoperative Complications in Obstructive Sleep Apnea: Importance of Phenotypes. Anesth Analg. 2021 May 1;132(5):1328-1337. doi: 10.1213/ANE.0000000000005390.

  PMID: 33857975 BACKGROUND

• Reilly EK, Boon MS, Vimawala S, Chitguppi C, Patel J, Murphy K, Doghramji K, Nyquist GG, Rosen MR, Rabinowitz MR, Huntley CT. Tolerance of Continuous Positive Airway Pressure After Sinonasal Surgery. Laryngoscope. 2021 Mar;131(3):E1013-E1018. doi: 10.1002/lary.28968. Epub 2020 Sep 16.

  PMID: 32936959 BACKGROUND

• Perger E, Taranto Montemurro L, Rosa D, Vicini S, Marconi M, Zanotti L, Meriggi P, Azarbarzin A, Sands SA, Wellman A, Lombardi C, Parati G. Reboxetine Plus Oxybutynin for OSA Treatment: A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial. Chest. 2022 Jan;161(1):237-247. doi: 10.1016/j.chest.2021.08.080. Epub 2021 Sep 20.

  PMID: 34543665 BACKGROUND

• Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, Eckert DJ, White DP, Wellman A. The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial. Am J Respir Crit Care Med. 2019 May 15;199(10):1267-1276. doi: 10.1164/rccm.201808-1493OC.

  PMID: 30395486 BACKGROUND

• Lim R, Messineo L, Grunstein RR, Carberry JC, Eckert DJ. The noradrenergic agent reboxetine plus the antimuscarinic hyoscine butylbromide reduces sleep apnoea severity: a double-blind, placebo-controlled, randomised crossover trial. J Physiol. 2021 Sep;599(17):4183-4195. doi: 10.1113/JP281912. Epub 2021 Jul 14.

  PMID: 34174090 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Reboxetine; Tablets; Sugars

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Carbohydrates

Study Officials

• Danny J. Eckert, PhD

  Flinders University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emma Thomas

CONTACT

+61882012912; ethomas@flinders.edu.au

Carolin Tran

CONTACT

+61874219873; carolin.tran@flinders.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical capsule for placebo and study drug prepared by study pharmacist
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Adelaide Institute for Sleep Health

Model Details: Double-blind, randomized, placebo-controlled, cross-over study

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: August 7, 2023
• Study Start: August 10, 2023
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: At conclusion of the study and any related publications
• Access Criteria: IPD may be shared for research purposes on application to the chief investigator and subject to applicable ethical review.

Locations

AU (1)