An interventional study of Inhaled nitrous oxide in Preterm Delivery, Cervical Cerclage and Cervical Insufficiency, sponsored by Kaplan Medical Center. Not yet recruiting at 4 sites in Israel. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-08.
Sponsored by Kaplan Medical Center · Not applicable, Interventional, and Treatment
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:
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:
Cervical insufficiency is a recognized risk factor for spontaneous preterm birth, which remains a major cause of perinatal morbidity and mortality worldwide. Cervical cerclage is an established intervention used in carefully selected patients to reduce the risk of preterm birth.
While cerclage placement is typically performed under anesthesia in the operating room, cerclage removal is usually carried out in the outpatient setting during the late third trimester of pregnancy. Despite being a brief procedure, many patients experience pain, discomfort, and anxiety during cerclage removal. Evidence regarding optimal pain management strategies for this procedure remains limited, and most patients currently undergo cerclage removal without analgesia.
Nitrous oxide (N₂O) is an inhaled gas with well-established analgesic and anxiolytic properties. It has a rapid onset and offset of action and a favorable safety profile. Nitrous oxide is widely used in obstetrics, particularly for labor analgesia, and has also been used for pain management during minor medical procedures. However, its use specifically for cervical cerclage removal has not been well studied.
This study is a multicenter randomized controlled trial designed to evaluate whether inhaled nitrous oxide reduces pain and anxiety during elective cervical cerclage removal. Participants will be randomly assigned in a 1:1 ratio to receive either inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) during the procedure or standard care without analgesic treatment, as routinely practiced in the participating institutions. Randomization will be stratified by site and implemented using sequentially numbered sealed envelopes opened immediately prior to the procedure.
All procedures will be performed according to routine clinical practice in the participating centers. Maternal and procedural data will be collected from medical records, including procedure duration, maternal vital signs, and any reported side effects such as nausea, dizziness, or headache. Pain intensity will be assessed using a 0-100 mm visual analog scale (VAS), and anxiety levels will be evaluated using the State-Trait Anxiety Inventory (STAI). Additional outcomes will include maternal heart rate during the procedure and patient satisfaction with the procedure.
This trial aims to determine whether inhaled nitrous oxide can effectively reduce pain and anxiety during cervical cerclage removal. The findings of this study may provide evidence to support improved pain management strategies for this procedure and may contribute to enhancing patient experience during cerclage removal.
2,550 studies on the registry are indexed under Premature Birth; 500 are open to participants now.
This study's planned enrollment of 60 is below the median of 84 across 1,666 interventional studies indexed under Premature Birth.
Browse Premature Birth studies →Kaplan Medical Center is the lead sponsor of 37 studies on the registry; 3 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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
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.
Time frame: 3-5 minutes following completion of the procedure
Difference between expected pain and experienced pain
Expected and experienced pain will be assessed using a 0-100 mm Visual Analog Scale (VAS), where higher scores indicate greater pain intensity. The difference between expected and experienced pain scores will be calculated.
Time frame: Baseline (prior to procedure) and 3-5 minutes following completion of the procedure
Procedure duration
Total duration of the cerclage removal procedure, measured in minutes from the beginning of the procedure to completion.
Time frame: During procedure
Change in maternal heart rate during procedure
Difference (delta) between baseline maternal heart rate and the maximal heart rate recorded during the procedure
Time frame: Baseline measurement prior to the procedure and continuous monitoring during the procedure
Change in anxiety level (STAI)
Anxiety levels will be assessed using the State-Trait Anxiety Inventory (STAI). The STAI score ranges from 20 to 80, with higher scores indicating higher levels of anxiety. Participants will complete the questionnaire before the procedure and again after cerclage removal. The change in STAI score will be analyzed.
Time frame: Baseline (before procedure) and 3-5 minutes after completion of the procedure
Patient satisfaction
Patient satisfaction will be assessed using a 5-point Likert scale, where 1 indicates very low satisfaction and 5 indicates very high satisfaction. The questionnaire will be completed after cerclage removal.
Time frame: 3-5 minutes after completion of the procedure
Adverse events
Occurrence of adverse events including nausea, dizziness, headache, or dyspnea reported during or immediately after the procedure
Time frame: During procedure
Conversion to neuraxial or general anesthesia
Need to convert from the assigned study condition (nitrous oxide or no analgesia) to epidural, spinal, or general anesthesia due to inability to complete the procedure
Time frame: During the procedure
Physician-rated procedural difficulty
The performing physician will provide a subjective assessment of the technical difficulty of cervical cerclage removal. Procedural difficulty will be assessed using a 5-point Likert scale, where 1 indicates very easy and 5 indicates very difficult.
Time frame: 3-5 minutes following completion of the procedure
Plan to share: Undecided
Start is estimated for May 2026; primary completion for May 2028, 24 months later.
Of 741 non-industry interventional studies with no phase under Premature Birth, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 47. This study's planned 24 months is close to that.
Counting every sponsor, half of 759 studies reached it within 24 months; a quarter within 12 and three quarters within 47.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Nitrous Oxide
Kaplan Medical Center