Use of Nitrous Oxide for Pain and Anxiety Management During Cervical Cerclage Removal

NCT07491874 | Not Yet Recruiting

• 1 other identifier: 0034-26-KMC1-C
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to determine whether inhaled nitrous oxide can reduce pain and anxiety during cervical cerclage removal compared with standard care. Cervical cerclage removal is commonly performed in the outpatient setting during the third trimester of pregnancy and may be associated with discomfort and anxiety despite being a brief procedure. The study will include pregnant women aged 18 years or older undergoing elective cervical cerclage removal at 36 weeks of gestation or later. The main questions the study aims to answer are:

• Does inhaled nitrous oxide reduce pain during cervical cerclage removal?
• Does inhaled nitrous oxide reduce anxiety during the procedure?
• Does the use of nitrous oxide improve overall patient satisfaction during cerclage removal? Researchers will compare women receiving inhaled nitrous oxide to those receiving standard care without analgesia, as routinely practiced in the participating institutions, in order to determine whether nitrous oxide improves pain control and patient experience during the procedure. Participants will:
• Be randomly assigned to receive either inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) or standard care without analgesic treatment during cervical cerclage removal.
• Undergo the procedure according to routine clinical practice in the participating centers.
• Complete questionnaires assessing pain and anxiety, including a visual analog scale (VAS) for pain and the State-Trait Anxiety Inventory (STAI).
• Have routine clinical data recorded from their medical records, including maternal vital signs and any procedure-related side effects.

Conditions

Preterm Delivery; Cervical Cerclage; Cervical Insufficiency

Outcome Measures

Primary Outcomes (1)

• Pain intensity during cervical cerclage removal

  Pain intensity will be assessed using a 0-100 mm visual analog scale (VAS). Participants will rate the level of pain experienced during the procedure 3-5 minutes after completion of the cerclage removal.

  3-5 minutes following completion of the procedure

Secondary Outcomes (8)

• Difference between expected pain and experienced pain

  Baseline (prior to procedure) and 3-5 minutes following completion of the procedure

• Procedure duration

  During procedure

• Change in maternal heart rate during procedure

  Baseline measurement prior to the procedure and continuous monitoring during the procedure

• Change in anxiety level (STAI)

  Baseline (before procedure) and 3-5 minutes after completion of the procedure

• Patient satisfaction

  3-5 minutes after completion of the procedure

Study Arms (2)

Inhaled Nitrous Oxide During Cervical Cerclage Removal

EXPERIMENTAL

Participants in this arm will receive inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) administered via a demand-valve mask during cervical cerclage removal. The system includes a one-way valve and is self-administered by the patient, who holds the mask and inhales as needed. The equipment is identical to the device routinely used for labor analgesia in the participating institutions and will be operated and monitored by trained midwives experienced in nitrous oxide administration. Continuous pulse oximetry monitoring will be initiated prior to gas administration. Nitrous oxide inhalation will begin following instruction from the performing physician, and the procedure will start approximately three minutes after inhalation begins once adequate analgesia and anxiolysis are achieved. After completion of the procedure, nitrous oxide will be discontinued and the patient will breathe room air. The patient will remain in bed for approximately 15 minutes with fetal monitoring to conf

Drug: Inhaled nitrous oxide

Standard Care Without Analgesia

NO INTERVENTION

Participants in this arm will undergo cervical cerclage removal without analgesia, in accordance with the standard practice across the participating institutions. The procedure will be performed in the outpatient setting following routine clinical protocols. Maternal vital signs and fetal status will be monitored according to standard clinical practice. No nitrous oxide or other analgesic intervention will be administered as part of the study protocol.

Interventions

Inhaled nitrous oxide DRUG

Inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) administered via a demand-valve mask during cervical cerclage removal. The system includes a one-way valve and is self-administered by the patient, who holds the mask and inhales as needed. The device is identical to the equipment routinely used for labor analgesia in the participating institutions and is operated and monitored by trained midwives experienced in nitrous oxide administration. Nitrous oxide inhalation begins following instruction from the performing physician. The procedure starts approximately three minutes after inhalation begins, once adequate analgesia and anxiolysis are achieved. Continuous pulse oximetry monitoring is performed during administration. After completion of the procedure, nitrous oxide is discontinued and the patient breathes room air.

Also known as: N2O

Inhaled Nitrous Oxide During Cervical Cerclage Removal

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Women at ≥34 weeks of gestation
• Singleton or twin pregnancy
• Ability to understand, sign informed consent, and complete questionnaires

You may not qualify if:

• Triplet or higher-order pregnancy
• Contraindications to nitrous oxide use
• Fetal monitoring category 2 or higher
• Maternal body temperature \>38°C
• Significant vaginal bleeding
• Severe preeclampsia
• Cerclage removal under general anesthesia
• Language or cognitive barrier
• Baseline pain \>3 on VAS scale, prior to the procedure

Sponsors & Collaborators

• Kaplan Medical Center: lead
• Clalit Health Services: collaborator
• Wolfson Medical Center: collaborator
• Rabin Medical Center: collaborator
• Meir Medical Center: collaborator

Study Sites (4)

Kaplan Medical Center

Rehovot, Central District, 7639302, Israel

Location

Edith Wolfson Medical Center

Holon, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Related Publications (19)

• Teichman Y. and Mellik H. (1976). "State-Trait Anxiety Inventory," Tel-Aviv University, Ramot Press

  BACKGROUND

• American College of Emergency Physicians. Managing Acute Pain in the ED - Nitrous Oxide. ACEP // Nitrous Oxide (viewed July 2021)

  BACKGROUND

• Spielberger, C., Gorsuch, R., & Lushene, R. (1970). Manual for the State-Trait Anxiety Inventory

  BACKGROUND

• Rosen MA. Nitrous oxide for relief of labor pain: a systematic review. Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S110-26. doi: 10.1067/mob.2002.121259.

  PMID: 12011877 BACKGROUND

• Del Valle Rubido C, Solano Calvo JA, Rodriguez Miguel A, Delgado Espeja JJ, Gonzalez Hinojosa J, Zapico Goni A. Inhalation analgesia with nitrous oxide versus other analgesic techniques in hysteroscopic polypectomy: a pilot study. J Minim Invasive Gynecol. 2015 May-Jun;22(4):595-600. doi: 10.1016/j.jmig.2015.01.005. Epub 2015 Jan 14.

  PMID: 25596171 BACKGROUND

• Stewart RD. Nitrous oxide sedation/analgesia in emergency medicine. Ann Emerg Med. 1985 Feb;14(2):139-48. doi: 10.1016/s0196-0644(85)81077-5.

  PMID: 4038592 BACKGROUND

• Veger ML, van Iterson J, Bakx R, Ridderikhof ML. The Role of Nitrous Oxide in Minor Pediatric Procedures in the Emergency Department: A Systematic Review. J Pediatr Surg. 2024 Jun;59(6):1154-1162. doi: 10.1016/j.jpedsurg.2023.12.026. Epub 2024 Jan 14.

  PMID: 38368199 BACKGROUND

• Pain Management for In-Office Uterine and Cervical Procedures: ACOG Clinical Consensus No. 9. Obstet Gynecol. 2025 May 15;146(1):161-177. doi: 10.1097/AOG.0000000000005911.

  PMID: 40373312 BACKGROUND

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• Fowler KG, Byraiah G, Burt C, Lee DB, Miller RJ. Nitrous Oxide Use for Intrauterine System Placement in Adolescents. J Pediatr Adolesc Gynecol. 2022 Apr;35(2):159-164. doi: 10.1016/j.jpag.2021.10.019. Epub 2021 Nov 6.

  PMID: 34748915 BACKGROUND

• Solano Calvo JA, Del Valle Rubido C, Rodriguez-Miguel A, de Abajo FJ, Delgado Espeja JJ, Gonzalez Hinojosa J, Fernandez Munoz L, Zapico Goni A. Nitrous oxide versus lidocaine versus no analgesic for in-office hysteroscopy: a randomised clinical trial. BJOG. 2021 Jul;128(8):1364-1372. doi: 10.1111/1471-0528.16657. Epub 2021 Mar 9.

  PMID: 33528862 BACKGROUND

• Schneider EN, Riley R, Espey E, Mishra SI, Singh RH. Nitrous oxide for pain management during in-office hysteroscopic sterilization: a randomized controlled trial. Contraception. 2017 Mar;95(3):239-244. doi: 10.1016/j.contraception.2016.09.006. Epub 2016 Sep 9.

  PMID: 27621048 BACKGROUND

• Giouleka S, Boureka E, Tsakiridis I, Siargkas A, Mamopoulos A, Kalogiannidis I, Athanasiadis A, Dagklis T. Cervical Cerclage: A Comprehensive Review of Major Guidelines. Obstet Gynecol Surv. 2023 Sep;78(9):544-553. doi: 10.1097/OGX.0000000000001182.

  PMID: 37976303 BACKGROUND

• ACOG Practice Bulletin No.142: Cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014 Feb;123(2 Pt 1):372-379. doi: 10.1097/01.AOG.0000443276.68274.cc.

  PMID: 24451674 BACKGROUND

• Ioscovich A, Popov A, Gimelfarb Y, Gozal Y, Orbach-Zinger S, Shapiro J, Ginosar Y. Anesthetic management of prophylactic cervical cerclage: a retrospective multicenter cohort study. Arch Gynecol Obstet. 2015 Mar;291(3):509-12. doi: 10.1007/s00404-014-3391-5. Epub 2014 Aug 8.

  PMID: 25103960 BACKGROUND

• Moawad GN, Tyan P, Bracke T, Abi Khalil ED, Vargas V, Gimovsky A, Marfori C. Systematic Review of Transabdominal Cerclage Placed via Laparoscopy for the Prevention of Preterm Birth. J Minim Invasive Gynecol. 2018 Feb;25(2):277-286. doi: 10.1016/j.jmig.2017.07.021. Epub 2017 Aug 7.

  PMID: 28797657 BACKGROUND

• Yorifuji T, Makino S, Yamamoto Y, Tanaka T, Itakura A, Takeda S. Effectiveness of delayed absorbable monofilament suture in emergency cerclage. Taiwan J Obstet Gynecol. 2014 Sep;53(3):382-4. doi: 10.1016/j.tjog.2014.04.023.

  PMID: 25286795 BACKGROUND

• Eleje GU, Eke AC, Ikechebelu JI, Ezebialu IU, Okam PC, Ilika CP. Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies. Cochrane Database Syst Rev. 2020 Sep 24;9(9):CD012871. doi: 10.1002/14651858.CD012871.pub2.

  PMID: 32970845 BACKGROUND

• Romero R, Yeo L, Miranda J, Hassan SS, Conde-Agudelo A, Chaiworapongsa T. A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix. J Perinat Med. 2013 Jan;41(1):27-44. doi: 10.1515/jpm-2012-0272.

  PMID: 23314512 BACKGROUND

MeSH Terms

Conditions

Premature Birth; Uterine Cervical Incompetence

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Abortion, Habitual; Abortion, Spontaneous; Genital Diseases

Central Study Contacts

Gil Friedman

CONTACT

+972584744356; gilfriedman51@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, OB-GYN Resident

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 25, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-03

Locations

IL (4)