NIUD: Nitrous Oxide for Pain Management of Intrauterine Device (IUD) Insertion

• Sponsor: University of New Mexico (Other)
• Overall Status: Completed
• CT.gov ID: NCT02391714
• Collaborator: Society of Family Planning (Other)
• Enrollment: 80
• Location: 1
• Arms: 2
• Duration (Months): 10
• Patients Per Site Per Month: 8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Nitrous Oxide is effective in achieving pain control and satisfaction among nulliparous women getting the intrauterine device (IUD).

Condition or Disease	Intervention/Treatment	Phase
Contraception	Procedure: IUD insertion; Drug: Povidone-Iodine; Drug: Chlorhexidine; Other: Oxygen; Other: Nitrous oxide	N/A

Detailed Description

Long acting reversible contraception (LARC) including the IUD provides several advantages that may be attractive to women. These include non-daily use, rapid reversibility and low failure rates. The American College of Obstetricians and Gynecologists (ACOG) endorses the use of IUDs among adolescents and nulliparous women, dispelling the myth that IUD use is contraindicated in this population.

Rates of IUD uptake among nulliparous women have not been reported. There are some barriers that may help explain the low uptake of IUDs by teens and nulliparous women, including fear of pain during IUD insertion. This concern is also voiced by providers who perceive pain with IUD insertion to be higher among nulliparous women (Allen, Goldberg et al. 2009).

There is limited evidence comparing subjective pain scores with IUD insertion between nulliparous versus parous women. However, there have been a number of studies evaluating the efficacy of misoprostol, non steroidal anti-inflammatory drugs and local anesthesia in reducing pain during IUD insertion. These included comparisons of pain scores between both nulliparous and multiparous women and reported pain scores by group. These studies have failed to demonstrate evidence that any of the aforementioned interventions significantly reduce pain scores compared to placebo (Allen et al. 2009). We conclude that pain with IUD insertion among nulliparous and adolescent women is within the high range of pain scale measurement standards. Therefore, further investigations of optimizing pain management during this procedure are warranted in order to lead to increased acceptability and adoption of IUDs among this population of women.

Nitrous oxide (NO) is an inhaled gas administered with oxygen in a fixed ratio for analgesia and sedation. It has been used for many years for procedural analgesia and anesthesia in outpatient settings and it reduces anxiety, the perception of pain and alters consciousness. It is attractive for the clinic setting as it demonstrates rapid induction and rapid resolution, allows for patient control of use, exhibits few side effects and boasts a benign safety profile in the setting of scavenging systems and open air clinics. Furthermore, NO systems are relatively inexpensive and noninvasive.

For all these reasons, NO seems to be an ideal approach for pain management with IUD insertion for nulliparous women. No studies have investigated the use of NO in this context. The aim of our study is to objectively identify pain reduction scores and satisfaction with NO use compared to typical insertion practices during IUD insertion for nulliparous women.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Nitrous Oxide for Pain Management of Intrauterine Device Insertion
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Oxygen (Placebo) 100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique.	Procedure: IUD insertion; The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer.; Other Names: Mirena® insertion ParaGard® insertion ; Drug: Povidone-Iodine; Povidone-Iodine 10% w/w antiseptic swab for the cervix prior to IUD insertion.; Other Names: PDI® ; Drug: Chlorhexidine; For patients with allergy to iodine - 2% w/v chlorhexidine gluconate and 70% v/v isopropyl alcohol antiseptic swab for the cervix prior to IUD insertion.; Other Names: ChloraPrep® ; Other: Oxygen; 100% oxygen via nasal mask.
Experimental: Nitrous Oxide (NO) Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique.	Procedure: IUD insertion; The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer.; Other Names: Mirena® insertion ParaGard® insertion ; Drug: Povidone-Iodine; Povidone-Iodine 10% w/w antiseptic swab for the cervix prior to IUD insertion.; Other Names: PDI® ; Drug: Chlorhexidine; For patients with allergy to iodine - 2% w/v chlorhexidine gluconate and 70% v/v isopropyl alcohol antiseptic swab for the cervix prior to IUD insertion.; Other Names: ChloraPrep® ; Other: Nitrous oxide; Given in a fixed dose ratio of 50% nitrous oxide/50% oxygen via nasal mask.

Outcome Measures

Primary Outcome Measures

1. Mean Maximum Procedural Pain Scores [2 minutes after the procedure.]

   Pain is assessed using a 0-100mm VAS with anchors 0 equals no pain and 100 equals worst pain imaginable. The minimal clinically important difference in pain for this study was set at 15mm.

Secondary Outcome Measures

1. Patient Satisfaction With Over-all Pain Control With IUD Insertion - VAS [Prior to clinic discharge, which is an average of 15 minutes after the procedure]

   Satisfaction will be measured using a 100mm Visual Analog Scale (VAS), with anchors 0mm for very satisfied and 100mm for very dissatisfied.

2. Baseline Mean Pain Scores [Before the IUD insertion procedure]

   Baseline pain scores prior to IUD insertion is assessed using a 0-100mm VAS with anchors 0 equals no pain and 100 equals worst pain imaginable. The minimal clinically important difference in pain for this study was set at 15mm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age >18 OR between the ages of 12-17 with a parent/legal guardian who can consent

• English speaking

• Desires a Mirena® or ParaGard® IUD

• Nulliparous woman

• Can use laughing gas

• Has not taken narcotic pain medications prior to procedure

Exclusion Criteria:

• Currently pregnant

• If you have been pregnant before, pregnancy lasting longer than 19 weeks, 6 days

• Less than 4 weeks have elapsed from the end of a spontaneous abortion or medical abortion.

• Desires Skyla® IUD

• Pelvic Inflammatory Disease in the last 3 months

• Current mucopurulent discharge

• Uterine anomaly that distorts the uterine cavity

• Known uterine fibroid with disruption of the uterine cavity

• Copper allergy/Wilson's disease (for ParaGard®)

• Current cervical or uterine cancer

• Inability to breathe through the nose

• Significant active upper airway infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Reproductive Health	Albuquerque	New Mexico	United States	87106

Sponsors and Collaborators

• University of New Mexico
• Society of Family Planning

Investigators

• Principal Investigator: Rameet Singh, MD MPH, UNM Division of Family Planning

Study Documents (Full-Text)

None provided.

More Information

Publications

• Allen RH, Bartz D, Grimes DA, Hubacher D, O'Brien P. Interventions for pain with intrauterine device insertion. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007373. doi: 10.1002/14651858.CD007373.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;7:CD007373.
• Allen RH, Goldberg AB, Grimes DA. Expanding access to intrauterine contraception. Am J Obstet Gynecol. 2009 Nov;201(5):456.e1-5. doi: 10.1016/j.ajog.2009.04.027. Epub 2009 Jun 13.

• Responsible Party: University of New Mexico
• ClinicalTrials.gov Identifier: NCT02391714
• Other Study ID Numbers: UNMHSC 13-289
• First Posted: Mar 18, 2015
• Last Update Posted: Feb 3, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by University of New Mexico: pain assessment; patient satisfaction; Visual Analog Scale; contraceptive devices; nulliparity
• Additional relevant MeSH terms: Chlorhexidine; Povidone-Iodine; Nitrous Oxide; Povidone

Study Results

Participant Flow

Arm/Group Title	Oxygen (Placebo)	Nitrous Oxide (NO)
Arm/Group Description	100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Oxygen: 100% oxygen via nasal mask.	Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Nitrous oxide: Given in a fixed dose ratio of 50% nitrous oxide/50% oxygen via nasal mask.
Period Title: Overall Study
STARTED	40	40
COMPLETED	40	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Oxygen (Placebo)	Nitrous Oxide (NO)	Total
Arm/Group Description	100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Oxygen: 100% oxygen via nasal mask.	Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Nitrous oxide: Given in a fixed dose ratio of 50% nitrous oxide/50% oxygen via nasal mask.	Total of all reporting groups
Overall Participants	40	40	80
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	26.3	24.93	25.62
Sex: Female, Male (Count of Participants)
Female	40 100%	40 100%	80 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%	40 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Mean Maximum Procedural Pain Scores
Description	Pain is assessed using a 0-100mm VAS with anchors 0 equals no pain and 100 equals worst pain imaginable. The minimal clinically important difference in pain for this study was set at 15mm.
Time Frame	2 minutes after the procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxygen (Placebo)	Nitrous Oxide (NO)
Arm/Group Description	100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Oxygen: 100% oxygen via nasal mask.	Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Nitrous oxide: Given in a fixed dose ratio of 50% nitrous oxide/50% oxygen via nasal mask.
Measure Participants	40	40
Mean (Standard Deviation) [units on a scale]	55.3 (20.9)	54.3 (24.8)

2. Secondary Outcome

Title	Patient Satisfaction With Over-all Pain Control With IUD Insertion - VAS
Description	Satisfaction will be measured using a 100mm Visual Analog Scale (VAS), with anchors 0mm for very satisfied and 100mm for very dissatisfied.
Time Frame	Prior to clinic discharge, which is an average of 15 minutes after the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxygen (Placebo)	Nitrous Oxide (NO)
Arm/Group Description	100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Povidone-Iodine: Povidone-Iodine 10% w/w antiseptic swab for the cervix prior to IUD insertion. Chlorhexidine: For patients with allergy to iodine - 2% w/v chlorhexidine gluconate and 70% v/v isopropyl alcohol antiseptic	Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Povidone-Iodine: Povidone-Iodine 10% w/w antiseptic swab for the cervix prior to IUD insertion. Chlorhexidine: For patients
Measure Participants	40	40
Mean (Standard Deviation) [units on a scale]	60.3 (26.6)	66.0 (32.2)

3. Secondary Outcome

Title	Baseline Mean Pain Scores
Description	Baseline pain scores prior to IUD insertion is assessed using a 0-100mm VAS with anchors 0 equals no pain and 100 equals worst pain imaginable. The minimal clinically important difference in pain for this study was set at 15mm.
Time Frame	Before the IUD insertion procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxygen (Placebo)	Nitrous Oxide (NO)
Arm/Group Description	100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Povidone-Iodine: Povidone-Iodine 10% w/w antiseptic swab for the cervix prior to IUD insertion. Chlorhexidine: For patients with allergy to iodine - 2% w/v chlorhexidine gluconate and 70% v/v isopropyl alcohol antiseptic	Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Povidone-Iodine: Povidone-Iodine 10% w/w antiseptic swab for the cervix prior to IUD insertion. Chlorhexidine: For patients
Measure Participants	40	40
Mean (Standard Deviation) [units on a scale]	1.9 (4.6)	2.4 (4.1)

Adverse Events

Arm/Group Title	Oxygen (Placebo)		Nitrous Oxide (NO)
Arm/Group Description	100% oxygen will be administered via disposable scented nasal masks 2 minutes before, throughout and 3-5 minutes after procedure. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Oxygen: 100% oxygen via nasal mask.		Nitrous Oxide in a fixed dose ratio of 50% nitrous/50% oxygen will be administered via disposable scented nasal masks 2 minutes before and throughout the procedure; 100% oxygen will be given after the procedure for 3-5 minutes. If you are randomized to this group, you will undergo the IUD insertion (including Povidone-Iodine or Chlorhexidine swab) using standard technique. IUD insertion: The IUD (Mirena® or ParaGard®) insertion procedure will occur in the usual manner for both arms. A bimanual exam will be performed, the speculum placed and the cervix visualized. The cervix will then by cleaned with iodine solution. If you are allergic to iodine, we will use chlorhexidine instead. A tenaculum will be placed on the cervix and a uterine sound will be used to measure cavity length. The Mirena® or ParaGard® IUD will be inserted with the specific introducer. Nitrous oxide: Given in a fixed dose ratio of 50% nitrous oxide/50% oxygen via nasal mask.
All Cause Mortality
	Oxygen (Placebo)		Nitrous Oxide (NO)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oxygen (Placebo)		Nitrous Oxide (NO)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Oxygen (Placebo)		Nitrous Oxide (NO)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.