Reboxetine for Sleep Apnoea After ENT Surgery

Sleep Apnea, Obstructive Clinical Trial

— RENTOSA  

Official title:

Reboxetine for Obstructive Sleep Apnoea After Upper Airway Surgery: a Randomised, Double-blind, Placebo-controlled Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05978505
• Other study ID #: 2023/HRE00060
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 15, 2023
• Est. completion date: December 2024

Study information

• Verified date: July 2023
• Source: Flinders University
• Contact: Emma J Thomas
• Phone: +61 8 8201 2912
• Email: ethomas[@]flinders.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years

• Undergoing elective upper airway surgery

• History of obstructive sleep apnoea (OSA)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Reboxetine 4 MG Oral Tablet
7 nightly doses (4mg) to commence after surgery.
• Placebo
7 nightly doses to commence after surgery.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Flinders University	Flinders Medical Centre

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Anesthesiology. 2014 May;120(5):1302. Anesthesiology. 2014 May;120(5):1302. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Reboxetine-related side effects	Documented via adverse-event forms.	14 days
Primary	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
Primary	Data capture efficiency	The percentage of successful data collection nights versus missed nights of at-home oximetry for this feasibility study.	14 days
Secondary	Oxygen desaturation index (ODI)	Number of times per hour that a participant has a drop in blood oxygen levels during sleep	14 days
Secondary	nadir SpO2	The lowest oxygen saturation value the patient drops to in a night.	14 days
Secondary	Time spent below 90% SpO2	The total amount of time per night for which oxygen saturation falls below 90%.	14 days
Secondary	mean SpO2	Average nightly oxygen level	14 days
Secondary	Sleep duration	Total amount of time spent asleep per night, sleep tracking performed using an under mattress sensor device.	14 days
Secondary	Sleep efficiency (%)	The estimated percentage of time in bed spent asleep performed using an under mattress sensor device.	14 days
Secondary	Daytime sleepiness	Measured via Karolinska Sleepiness Scale Questionnaire (9 point scale where 1 = extremely alert and 9 = extremely sleepy - fighting sleep)	14 days
Secondary	Perceived sleep quality measured via the Leeds Sleep Evaluation Questionnaire	This questionnaire asks participants to rate their perceived sleep across 4 domains on a visual analog scale as follows: 1) getting to sleep, 2) quality of sleep, 3) Awake following sleep, 4) Behavior following wakening. Higher scores indicate better perceived sleep.	14 days
Secondary	Insomnia Severity Score	A patient-reported measure of insomnia symptoms using the Insomnia Severity Index- A 28 point scale where 0 indicates no clinically significant insomnia and 28 indicates maximally severe clinical insomnia.	14 days
Secondary	Apnoea-hypopnea hndex (AHI)	Change in OSA severity (AHI estimated via the Withings under mattress sensor number of events/hour) between placebo and reboxetine	14 days
Secondary	Study enrolment rate	The number of referred patients successfully enrolled into this feasibility study	12 months