Methoxyflurane for Analgesia During Hysteroscopy

NCT06899724 | Not Yet Recruiting DMC

• 1 other identifier: JThiel2
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to assess the non-inferiority of using inhaled methoxyflurane (MOF) versus intravenous conscious sedation with fentanyl and midazolam on women's perception of pain, during hysteroscopy and/or polypectomy in an outpatient setting. The researchers will determine whether the participants receiving the inhaled MOF (experimental group) achieve similar clinical effects in reduction of pain and ability to complete the procedure. Women's perception of pain will be recorded on a scale from 0 to 10 using the numeric rating scale (NRS).

Conditions

Analgesia

Outcome Measures

Primary Outcomes (1)

• Patient analgesia

  Patients will rate their pain on a Numeric Rating Scale during the procedure

  15, 30 and 60 seconds

Secondary Outcomes (5)

• Time to complete procedure

  15 minutes

• Pain one hour post procedure

  60 minutes post procedure

• Rescue analgesia

  60 minutes

• Acceptability of the procedure

  60 minutes

• Time to discharge

  60 minutes

Study Arms (4)

IV Sedation

ACTIVE COMPARATOR

Patients will receive 1 microgram/kg fentanyl and 1 - 3 mg midazolam intravenously as per the normal intravenous sedation protocol

Drug: Intravenous Sedatives with or Without Analgesia

Methoxyflurane

ACTIVE COMPARATOR

Patients will receive three inhalations from the green whistle loaded with methoxyflurane

Drug: Anesthetics, Inhalation

IV saline

PLACEBO COMPARATOR

Patients in the Methoxyflurane group will receive intravenous saline administered from the same syringes as those in the fentanyl and midazolam group

Drug: Anesthetics, Inhalation

Inhaled saline

PLACEBO COMPARATOR

Patients in the Intravenous sedation group will receive three inhalations of saline from a placebo loaded green whistle

Drug: Intravenous Sedatives with or Without Analgesia

Interventions

Anesthetics, Inhalation DRUG

Inhaled analgesia

Also known as: Methoxyflurane

IV saline; Methoxyflurane

Intravenous Sedatives with or Without Analgesia DRUG

IV Fentanyl and midazolam

IV Sedation; Inhaled saline

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Abnormal uterine Bleeding requiring hysteroscopy Postmenopausal bleeding requiring hysteroscopy

You may not qualify if:

• Uterine or patient characteristics that preclude hysteroscopy Submucosal fibroids requiring myomectomy Past allergic reaction to fentanyl or midazolam BMI \> 42 Contraindications precluding use of intravenous sedation (sleep apnea) Lack of patient consent History of malignant hyperthermia History of significant renal or hepatic disease

Sponsors & Collaborators

• Dr. John A. Thiel Medical Professional Corporation: lead

Study Sites (1)

University of Saskatchewan

Saskatoon, Saskatchewan, S7N 0W0, Canada

Location

Related Publications (23)

• 1. Penthrox product monograph. Paladin Labs Inc, 100 Alexis-Nihon Blvd, Suite 600, St-Laurent, Quebec, Canada.

  BACKGROUND

• Jephcott C, Grummet J, Nguyen N, Spruyt O. A review of the safety and efficacy of inhaled methoxyflurane as an analgesic for outpatient procedures. Br J Anaesth. 2018 May;120(5):1040-1048. doi: 10.1016/j.bja.2018.01.011. Epub 2018 Feb 12.

  PMID: 29661381 BACKGROUND

• Debuka E, Birkenhead P, Shah S, Narayan B, Giotakis N, Thorpe P, Graham SM, Fischer BE, Peterson N. Penthrox(R) (Methoxyflurane) as an Analgesic for Removal of Circular External Fixators and Minor Procedures during the COVID-19 Pandemic. Strategies Trauma Limb Reconstr. 2023 May-Aug;18(2):82-86. doi: 10.5005/jp-journals-10080-1587.

  PMID: 37942432 BACKGROUND

• Trimmel H, Egger A, Doppler R, Pimiskern M, Voelckel WG. Usability and effectiveness of inhaled methoxyflurane for prehospital analgesia - a prospective, observational study. BMC Emerg Med. 2022 Jan 15;22(1):8. doi: 10.1186/s12873-021-00565-6.

  PMID: 35033003 BACKGROUND

• Mercadante S, Voza A, Serra S, Ruggiano G, Carpinteri G, Gangitano G, Intelligente F, Bonafede E, Sblendido A, Farina A, Soldi A, Fabbri A; MEDITA Study Group. Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA). Adv Ther. 2019 Nov;36(11):3030-3046. doi: 10.1007/s12325-019-01055-9. Epub 2019 Oct 12.

  PMID: 31612359 BACKGROUND

• Locke JA, Neu S, Lawrence J, Herschorn S. Pilot study to assess the feasibility of self-administered, low-dose methoxyflurane for cystoscopic procedures. Can Urol Assoc J. 2024 Aug;18(8):251-254. doi: 10.5489/cuaj.8676.

  PMID: 38587974 BACKGROUND

• Nguyen NQ, Toscano L, Lawrence M, Moore J, Holloway RH, Bartholomeusz D, Lidums I, Tam W, Roberts-Thomson IC, Mahesh VN, Debreceni TL, Schoeman MN. Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized multicenter trial. Gastrointest Endosc. 2013 Dec;78(6):892-901. doi: 10.1016/j.gie.2013.05.023. Epub 2013 Jun 28.

  PMID: 23810328 BACKGROUND

• Nguyen NQ, Burgess J, Debreceni TL, Toscano L. Psychomotor and cognitive effects of 15-minute inhalation of methoxyflurane in healthy volunteers: implication for post-colonoscopy care. Endosc Int Open. 2016 Nov;4(11):E1171-E1177. doi: 10.1055/s-0042-115409. Epub 2016 Nov 8.

  PMID: 27853742 BACKGROUND

• Sairally BZF, Smith PP, De Silva PM, O'Connor S, Yates C, Clark TJ. Inhaled methoxyflurane (Penthrox(R)) as a novel pain relief for outpatient hysteroscopy and other gynaecological procedures. Eur J Obstet Gynecol Reprod Biol. 2024 Nov;302:206-210. doi: 10.1016/j.ejogrb.2024.09.002. Epub 2024 Sep 6.

  PMID: 39303369 BACKGROUND

• Ahmad G, Saluja S, O'Flynn H, Sorrentino A, Leach D, Watson A. Pain relief for outpatient hysteroscopy. Cochrane Database Syst Rev. 2017 Oct 5;(10)(10):CD007710. doi: 10.1002/14651858.CD007710.pub3.

  PMID: 35611933 BACKGROUND

• De Silva PM, Mahmud A, Smith PP, Clark TJ. Analgesia for Office Hysteroscopy: A Systematic Review and Meta-analysis. J Minim Invasive Gynecol. 2020 Jul-Aug;27(5):1034-1047. doi: 10.1016/j.jmig.2020.01.008. Epub 2020 Jan 23.

  PMID: 31982584 BACKGROUND

• Dias AV, Zeidan Z, Copp M, Eslabra F, Hassan R, Middleton R. Penthrox Is an Effective Analgesic but Is It Patient Approved? Cureus. 2024 Feb 4;16(2):e53537. doi: 10.7759/cureus.53537. eCollection 2024 Feb.

  PMID: 38445124 BACKGROUND

• Smith MD, Rowan E, Spaight R, Siriwardena AN. Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma: non-randomised clinical study. BMC Emerg Med. 2022 Jul 7;22(1):122. doi: 10.1186/s12873-022-00664-y.

  PMID: 35799131 BACKGROUND

• 14. Wong KY, JS Ki Lau, AY Chung Siu, PG Kan. A randomized non-inferiority pilot study on the use of methoxyflurane (Penthrox) for pain control in the emergency department. Hong Kong Journal of Emergency Medicine 29:203-211.

  BACKGROUND

• Elterman DS, Zorn KC, Bhojani N, Chughtai B. Efficacy and safety of methoxyflurane (Penthrox) for pain control during water vapor thermal therapy (Rezum) for benign prostatic enlargement. Can J Urol. 2022 Dec;29(6):11355-11360.

  PMID: 36495576 BACKGROUND

• Twidale EK, Neutens S, Hynt L, Dudley N, Streeton C. Methoxyflurane analgesia for outpatient hysteroscopy: A double-blind, randomised, controlled trial. Aust N Z J Obstet Gynaecol. 2025 Feb;65(1):69-76. doi: 10.1111/ajo.13861. Epub 2024 Jul 15.

  PMID: 39007504 BACKGROUND

• Stewart AJ, Brooker C, Vose G, Redmond K, Williams A, Pankhania N, Dommett H, Kirk-Bayley J, Franklin AP, Morrison B. Pain and symptom relief using inhaled methoxyflurane for gynecologic brachytherapy applicator removal. J Contemp Brachytherapy. 2023 Feb;15(1):37-42. doi: 10.5114/jcb.2023.125581. Epub 2023 Feb 28.

  PMID: 36970443 BACKGROUND

• Hayne D, Grummet J, Espinoza D, McCombie SP, Chalasani V, Ford KS, Frydenberg M, Gilling P, Gordon B, Hawks C, Konstantatos A, Martin AJ, Nixon A, O'Brien C, Patel MI, Sengupta S, Shahbaz S, Subramaniam S, Williams S, Woo HH, Stockler MR, Davis ID, Buchan N; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). 'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501). BJU Int. 2022 May;129(5):591-600. doi: 10.1111/bju.15552. Epub 2021 Jul 30.

  PMID: 34273231 BACKGROUND

• Copping R, Balamon P, Lau M, Catt J, Schlaphoff G. MethOxyfluraNe in InTerventiOnal Radiology (MONITOR): A randomised controlled trial. J Med Imaging Radiat Oncol. 2024 Sep;68(6):705-713. doi: 10.1111/1754-9485.13726. Epub 2024 Jun 25.

  PMID: 38923825 BACKGROUND

• Spruyt O, Westerman D, Milner A, Bressel M, Wein S. A randomised, double-blind, placebo-controlled study to assess the safety and efficacy of methoxyflurane for procedural pain of a bone marrow biopsy. BMJ Support Palliat Care. 2014 Dec;4(4):342-8. doi: 10.1136/bmjspcare-2013-000447. Epub 2013 Jun 7.

  PMID: 24644183 BACKGROUND

• Methoxyflurane Inhalation as an Analgesic for Minor Gynecological, Ambulatory, or Emergency Procedures: Rapid Review [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2024 Sep. Report No.: RC1545. Available from http://www.ncbi.nlm.nih.gov/books/NBK608473/

  PMID: 39466939 BACKGROUND

• Coffey F, Dissmann P, Mirza K, Lomax M. Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!). Adv Ther. 2016 Nov;33(11):2012-2031. doi: 10.1007/s12325-016-0405-7. Epub 2016 Aug 27.

  PMID: 27567918 BACKGROUND

• 23. Sealed Envelope Ltd. 2012. Power calculator for continuous outcome non-inferiority trial. [Online] Available from: https://www.sealedenvelope.com/power/continuous-noninferior/ [Accessed Wed Feb 05 2025].

  BACKGROUND

MeSH Terms

Conditions

Agnosia

Interventions

Anesthetics, Inhalation; Methoxyflurane; Analgesia

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Ethyl Ethers; Ethers; Organic Chemicals; Methyl Ethers; Anesthesia and Analgesia

Study Officials

• Peter S Thiel, MD MPH FRCSC

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John A Thiel, MD FRCSC

CONTACT

306-591-1773; drjthiel@aol.com

Darrien D Rattray, MD FRCSC

CONTACT

306-586-1800; darrien.rattray@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: After the interventions are assigned, an unblinded nurse will prepare the study medications according to each participant's identification number and treatment allocation group. Nursing staff in these clinics would normally prepare procedural medications. The nurse will prepare identical syringes filled with either fentanyl, midazolam, or normal saline, label the syringes with the participant identification number, and deliver them to the procedure room at the time of the scheduled hysteroscopy, confirming the patient's identity with the procedure team. They will also provide the Green Whistle and a vial of the methoxyflurane or saline. The physician, assisting nurses, and the participant will all be blinded to the identity of the medication in the syringe and the green whistle.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double blind placebo controlled non-inferiority study

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: March 28, 2025
• Study Start: June 1, 2025
• Primary Completion: December 31, 2025
• Study Completion: January 30, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)