An interventional study of Insertion of nitroglycerin ointment and Insertion of placebo ointment in Contraception and Pain, sponsored by Oregon Health and Science University. Completed at 2 sites in United States. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-04-26.
Sponsored by Oregon Health and Science University · Not applicable, Interventional, and Prevention
Increasing ease of access of long-acting birth control methods, like intrauterine devices (IUDs), is an important way to reduce the risk of unintended pregnancy. Unfortunately, fear of IUD insertion in women who have not had children is common among health care providers and women alike, and this limits IUD use. To increase acceptance of this highly effective birth control method, there is a need to explore new, low cost, and easily applied methods to improve the insertion experience. This is a pilot study to evaluate the effectiveness and acceptability of nitroglycerin ointment applied vaginally to improve the IUD insertion experience for both patient and provider. The investigators hypothesis is that nitroglycerin ointment will decrease the pain associated with IUD insertion.
Increasing acceptability and use of long acting reversible contraceptive methods like the intrauterine device (IUD) is an important strategy to reduce the risk of unintended pregnancy. Unfortunately, fear of IUD insertion in nulliparous women is common among health care providers and women alike, and this limits IUD use. While many health care providers assume that placement is more difficult in nulliparous women, there is no evidence that the risk of unsuccessful insertion is higher. Women worry about pain with insertion, and their fear is not unfounded as U.S. and international data have shown that nulliparous women report approximately twice as much pain with IUD insertion compared to parous women.
A key difference between nulliparous and multiparous women is the resistance of the cervix. While cervical dilation is uncommonly needed during IUD placement, force is often required to pass the insertion device through the internal os. Although misoprostol and ibuprofen have been studied as ways to improve the IUD insertion experience, neither has proved effective, and misoprostol actually has been shown to increase pain. Therefore, to increase acceptance of this highly effective contraceptive, there is a need to investigate novel, low cost, easily applied and accessible techniques to improve the insertion experience.
Nitric oxide (NO) donors, including nitroglycerin, nitroprusside, isosorbide mononitrate and isosorbide dinitrate, have effects on the animal and human cervix. Both nitroglycerin and isosorbide mononitrate tablets administered vaginally have been shown in RCTs to induce effective cervical ripening with minimal side effects for first trimester abortion compared to placebo. Nitroprusside and isosorbide dinitrate gel given intracervically prior to first trimester abortion also have showed minimal side effects in several RCTs, but with mixed results regarding effectiveness. Additional safety data about NO donors applied topically to skin and mucosal surfaces is well established through the routine use of topical nitroglycerin for treatment of anal fissures.
Although a recent randomized controlled trial (RCT) comparing nitroprusside gel to misoprostol for cervical ripening prior to first trimester surgical abortion found superior cervical dilation in the misoprostol group, there was no significant difference in cervical dilation up to 5 mm. While most studies of abortion are concerned with providing adequate dilation beyond 8 mm, the cervical remodeling that is necessary to help with IUD insertion is much less, as the levonorgestrel intrauterine system (LNG-IUS) inserter is only 4.75 mm in diameter. Since NO donors are smooth muscle relaxants, they are expected to induce cervical ripening without causing uterine cramping, which is the most significant side effect of misoprostol.
Nitroglycerin is inexpensive, stable at room temperature, and readily available in tablet and ointment form, as well as in a dextrose solution for intravenous administration. The ointment form is commonly applied topically for the treatment of anal fissures. We propose the following aims:
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Exclusion Criteria:
Drug: Insertion of nitroglycerin ointment
Drug: Insertion of placebo ointment
Nitroglycerin ointment inserted into the vagina 30-45 minutes prior to IUD insertion
Placebo ointment inserted into the vagina 30-45 minutes prior to IUD insertion
Patient-reported Pain at Passage of Insertion Device Through Cervix, as Measured on a 100 mm VAS
Patient-reported pain at passage of insertion device through cervix, as measured on a 100 mm VAS. VAS anchors: 0 indicates no pain, and 100 indicates worst pain imaginable.
Time frame: 30-45 minutes after insertion of nitroglycerin ointment
Provider Ease With Intrauterine Device Insertion Measured on a 100 mm VAS
Provider ease with intrauterine device insertion measured on a 100 mm VAS. VAS (visual analog scale) anchors: 0 indicates easiest insertion imaginable, 100 indicates most difficult insertion imaginable
Time frame: 30-45 minutes after insertion of nitroglycerin ointment
| Milestone | Active Nitroglycerin Ointment | Placebo Ointment |
|---|---|---|
| Started | 12 | 12 |
| Completed | 12 | 12 |
| Not completed | 0 | 0 |
Patient-reported pain at passage of insertion device through cervix, as measured on a 100 mm VAS. VAS anchors: 0 indicates no pain, and 100 indicates worst pain imaginable.
| mm | Active Nitroglycerin Ointment | Placebo Ointment |
|---|---|---|
| Patient-reported Pain at Passage of Insertion Device Through Cervix, as Measured on a 100 mm VAS | 55.8 ± 25.2 | 53.9 ± 28.1 |
Provider ease with intrauterine device insertion measured on a 100 mm VAS. VAS (visual analog scale) anchors: 0 indicates easiest insertion imaginable, 100 indicates most difficult insertion imaginable
| mm | Active Nitroglycerin Ointment | Placebo Ointment |
|---|---|---|
| Provider Ease With Intrauterine Device Insertion Measured on a 100 mm VAS | 29.4 ± 23.8 | 22.8 ± 29.9 |
Collected over 2 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active Nitroglycerin Ointment | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Placebo Ointment | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Age, Continuous(years) | Active Nitroglycerin Ointment | Placebo Ointment | Total |
|---|---|---|---|
| Mean | 28.3 ± 6.9 | 25.7 ± 4.4 | 27.04 ± 5.7 |
| Sex: Female, Male(Participants) | Active Nitroglycerin Ointment | Placebo Ointment | Total |
|---|---|---|---|
| Female | 12 | 12 | 24 |
| Male | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Active Nitroglycerin Ointment | Placebo Ointment | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 12 | 9 | 21 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 3 | 3 |
| Current smoker(Participants) | Active Nitroglycerin Ointment | Placebo Ointment | Total |
|---|---|---|---|
| Count of participants | 4 | 3 | 7 |
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