3 mL Inhaled Methoxyflurane for Intrauterine Device (IUD) Insertion

A Double-blind Placebo-controlled Randomized Controlled Trial (RCT) of 3 mL Inhaled Methoxyflurane for Intrauterine Device (IUD) Insertion

Intrauterine device (IUD) insertion is a common contraceptive procedure often associated with moderate to severe pain, particularly among nulliparous individuals. Current pain management strategies, such as over-the-counter analgesics, are frequently inadequate. Methoxyflurane, a short-acting, self-administered inhaled analgesic, has been shown to provide rapid and effective pain relief in acute and procedural settings. This study aims to evaluate whether 3 mL of inhaled Methoxyflurane (via Penthrox inhaler) improves patient satisfaction by reducing pain and anxiety during IUD insertion.

Study Overview

• Status: Recruiting
• Conditions: IUD
• Intervention / Treatment: Drug: Saline; Drug: Methoxyflurane

Detailed Description

Methoxyflurane is a short-acting, self-administered inhaled analgesic that has demonstrated rapid and effective pain relief in acute trauma, emergency, and procedural settings. It is non-narcotic, allows patients to control dosing, and does not require intravenous access or prolonged recovery, making it suitable for short outpatient procedures. Existing studies indicate that Methoxyflurane provides faster onset of pain relief compared to standard analgesics, is generally well-tolerated, and has only transient, non-serious adverse effects such as dizziness or headache.

This study aims to evaluate the efficacy of 3 mL of inhaled Methoxyflurane, delivered via Penthrox inhaler, in reducing pain and anxiety during IUD insertion. The primary objective is to assess patient satisfaction with pain management. Secondary outcomes include procedural pain scores, anxiety levels, and the incidence of adverse events. This trial seeks to provide evidence for an effective, safe, and patient-centered approach to pain management during IUD insertion, potentially improving patient experience and access to long-acting contraceptive options.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Didem Bozak; Phone Number: 6473814051; Email: didem.bozak@wchospital.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 1B2
      • Recruiting
      • Women's College Hospital
      • Contact: Didem Bozak; Phone Number: 416-323-6008; Email: didem.bozak@wchospital.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with a uterus.
2. Ages 18 to 55 years.
3. Undergoing any intrauterine device (IUD) insertion.
4. English-speaking participants.
5. Ability to use an inhaler device.
6. Willing to receive a cervical block for their IUD insertion

Exclusion Criteria:

1. Inability to provide informed consent.
2. Confirmed pregnancy.
3. Use of pain medication other than NSAIDs or acetaminophen (e.g., opioids, benzodiazepines, muscle relaxants) within 24 hours prior to the intervention.
4. Use of cannabis within 24 hours prior to the intervention.
5. Administration of misoprostol within 24 hours prior to the intervention.
6. Altered level of consciousness due to any cause, including head injury, drugs, or alcohol.
7. History of severe adverse reactions to Penthrox (methoxyflurane) or other halogenated anesthetic agents, or to any ingredient in the formulation (including non-medicinal ingredients or container components).
8. Anatomical variance, such as distorted uterine cavity, bicornuate uterus, uterus didelphys, or cervical stenosis.
9. Clinically significant renal and/or liver impairment.
10. Known or genetic susceptibility to malignant hyperthermia.
11. Clinically evident hemodynamic or cardiovascular instability, or respiratory depression.
12. Not NPO according to hospital guidelines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants will receive a Penthrox inhaler containing 3 mL of methoxyflurane. Before speculum insertion, they will take intermittent inhalations every 30-60 seconds (6-10 breaths), following monograph instructions. They may continue self-administering the inhaler as needed during the procedure. Participants will receive standard pain management prior to IUD insertion, which includes: 1) recommendation to use over-the-counter analgesics such as NSAIDs, and 2) the option to undergo a cervical block to minimize discomfort during the procedure.	Drug: Methoxyflurane; 3 mL of Methoxyflurane via a handheld inhaler; Other Names: Penthrox
Placebo Comparator: Placebo Group; Participants will receive an identical-looking inhaler containing 3 mL of normal saline. To maintain blinding, a drop of methoxyflurane will be placed on the outside of the device, which has no analgesic effect. Before speculum insertion, participants will take intermittent inhalations every 30-60 seconds (6-10 breaths), following monograph-style instructions, and may continue self-administering as needed during the procedure. Participants will receive standard pain management prior to IUD insertion, which includes: 1) recommendation to use over-the-counter analgesics such as NSAIDs, and 2) the option to undergo a cervical block to minimize discomfort during the procedure.	Drug: Saline; 3 mL of Normal Saline via an identical placebo handheld inhaler; Other Names: 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural pain intensity	Patient-reported pain will be measured using the Numeric Rating Scale (NRS), a validated tool in which participants rate their pain intensity on a scale from 0 (no pain) to 10 (worst imaginable pain).	20 minutes after post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction with pain management	Pain Catastrophizing Scale (PCS) Purpose: To measure the extent to which individuals magnify, ruminate about, or feel helpless in response to pain. Structure: 13 items rated on a 5-point Likert scale (0 = "not at all" to 4 = "all the time"). Items are grouped into three subscales: Rumination - Focused on the inability to stop thinking about pain. Magnification - Exaggeration of the threat value of pain. Helplessness - Perceived inability to manage pain. Scoring: Total PCS score ranges from 0 to 52. Higher scores indicate greater pain catastrophizing. Subscale scores can also be calculated for more nuanced insights.	Baseline before procedure
Symptom Reporting / Emergency Visits	Adverse Events recording	24 hours after post procedure
Patient-centered measure of satisfaction with procedural sedation	PROcedural Sedation Assessment Survey (PROSAS)	20 minutes after post procedure
Patient distress	Faces Anxiety Scale Faces are assigned numerical values (e.g., 0-5 or 0-10). Higher scores indicate greater anxiety.	Pre-procedure and post procedure 0,20 minutes and 24 hours.
Patient Anxiety	State-Trait Anxiety Inventory (STAI) Structure: 40 items in total: 20 items for State Anxiety (S-Anxiety) 20 items for Trait Anxiety (T-Anxiety) Respondents rate items on a 4-point Likert scale: For State Anxiety: 1 = "Not at all" to 4 = "Very much so" For Trait Anxiety: 1 = "Almost never" to 4 = "Almost always" Scoring: Each subscale (State and Trait) is scored separately. Higher scores indicate higher levels of anxiety. Scores can be used to track changes over time or to compare anxiety levels across groups.	Pre-procedure and post procedure 0,20 minutes and 24 hours.
Recall peak pain during procedure	Patient-reported pain will be measured using the Numeric Rating Scale (NRS), a validated tool in which participants rate their pain intensity on a scale from 0 (no pain) to 10 (worst imaginable pain).	0 minutes after post procedure
Provider-centered measure of satisfaction with procedural sedation	PROcedural Sedation Assessment Survey (PROSAS)	20 minutes after post procedure
Assess the effectiveness of blinding	Bang Blinding Index (BBI)- Patient, Assessor and Anesthesia provider	20 minutes after post procedure
Patient Satisfaction with Pain Management	Patient-reported satisfaction will be measured on a 5-point scale ranging from 0 (not satisfied) to 10 (very satisfied).	20 minutes after post procedure

Collaborators and Investigators

• Sponsor: Women's College Hospital
• Investigators: Principal Investigator: Karim Ladha, MD, Women's College Hospital; Principal Investigator: Lauren Scott, NP, Women's College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Methoxyflurane; Penthrox
• Additional Relevant MeSH Terms: Organic Chemicals; Ethers; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Methyl Ethers; Ethyl Ethers; Methoxyflurane; Sodium Chloride
• Other Study ID Numbers: 2025-0056-B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No