ContraceptionNCT01490073
The Effect of Nitroglycerin on the Intrauterine Device (IUD) Insertion Experience in Nulliparous Women
A study testing Insertion of nitroglycerin ointment in people with Contraception and Pain, run by Oregon Health and Science University at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception, Pain
- What is being tested?
- Insertion of nitroglycerin ointment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Mar 2012to 1 Nov 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- age 18-45 years,
- generally healthy,
- requesting a LNG-IUS for contraception as the primary indication
Who cannot join
- Previous pregnancy beyond 20 weeks;
- previous IUD placement or attempted IUD placement;
- previous cervical cold knife cone (CKC) or loop electrosurgical excision procedure (LEEP);
- contraindication to LNG-IUS (including pregnancy, fibroids that distort the uterine cavity, exam consistent with PID, allergy to any component of the LNG-IUS, etc);
- concurrent use of any form of nitrate therapy or medications that interact with nitroglycerin (such as phosphodiesterase V inhibitors);
- known allergy to nitroglycerine or common topical ointment ingredients;
Show all 15Show fewer
- known renal or hepatic impairment;
- history of hypertensive or hypotensive disorder;
- history of migraine, cluster headaches, or vascular headaches;
- history of myocardial infarction;
- uncontrolled congestive heart failure;
- unstable angina;
- tobacco or alcohol amblyopia;
- congenital optic atrophy;
- blood pressure less than 90/55 or greater than 150/100 in office prior to speculum exam
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Planned Parenthood Columbia Willamette
Portland, Oregon, 97212
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: The Effect of Nitroglycerin on the IUD Insertion Experience in Nulliparous Women: a Pilot Study
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.
Read the detailed description
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:
- To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD insertion improves pain among nulliparous women compared to a placebo ointment. Self-reported pain scores on a 100 mm VAS will be assessed at multiple time points during and after the IUD insertion procedure. In addition, overall satisfaction and adverse effects will be evaluated.
- To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD insertion improves ease of IUD insertion for the provider compared to a placebo ointment. In addition, need for additional dilation, additional pain medicine such as paracervical block, inability to place the IUD, and complications will be tracked.
- To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD insertion is safe and well tolerated. Side effects related to treatment with nitroglycerin ointment or placebo will be compared. Blood pressure will be measured at multiple time points.
- Conditions
- Contraception, Pain
- Being tested
- Insertion of nitroglycerin ointment, Insertion of placebo ointment
- Keywords
- Intrauterine device, Pain, Contraception, Nitroglycerin, Nitric oxide donor, Intrauterine device insertion
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insertion of nitroglycerin ointmentDrug
Nitroglycerin ointment inserted into the vagina 30-45 minutes prior to IUD insertion
Insertion of placebo ointmentDrug
Placebo ointment inserted into the vagina 30-45 minutes prior to IUD insertion
| Study group | Role | What they receive |
|---|---|---|
| Active nitroglycerin ointment | Active comparator | Not described Receives: Drug: Insertion of nitroglycerin ointment |
| Placebo ointment | Placebo comparator | Not described Receives: Drug: Insertion of placebo ointment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30-45 minutes after insertion of nitroglycerin ointment
Secondary outcomes (1)
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
Measured: 30-45 minutes after insertion of nitroglycerin ointment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2011 (estimated)
- Study start1 Mar 2012
- Primary completion1 Nov 2012
- Study completion1 Nov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- American College of Obstetricians and Gynecologists, Bayer
- Responsible party
- Principal investigator, Elizabeth Micks, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490073
- Sponsor's protocol ID
- 7928
- Status last verified
- Apr 2019
- First submitted
- 8 Dec 2011
- Last updated
- 26 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Nitroglycerin on the IUD Insertion Experience in Nulliparous Women: a Pilot Study
- ClinicalTrials.gov ID
- NCT01490073
- Acronym / sponsor ID
- 7928
- Conditions
- Contraception, Pain
- Keywords
- Intrauterine device, Pain, Contraception, Nitroglycerin, Nitric oxide donor, Intrauterine device insertion
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- American College of Obstetricians and Gynecologists, Bayer
- Study start
- 1 Mar 2012 (actual)
- Primary completion
- 1 Nov 2012 (actual)
- Study completion
- 1 Nov 2012 (actual)
- First posted
- 12 Dec 2011 (estimated)
- Results
- Posted 26 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD insertion improves pain among nulliparous women compared to a placebo ointment. Self-reported pain scores on a 100 mm VAS will be assessed at multiple time points during and after the IUD insertion procedure. In addition, overall satisfaction and adverse effects will be evaluated.
- To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD insertion improves ease of IUD insertion for the provider compared to a placebo ointment. In addition, need for additional dilation, additional pain medicine such as paracervical block, inability to place the IUD, and complications will be tracked.
- To determine if nitroglycerin ointment applied vaginally 30-45 minutes prior to IUD insertion is safe and well tolerated. Side effects related to treatment with nitroglycerin ointment or placebo will be compared. Blood pressure will be measured at multiple time points.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active nitroglycerin ointment | Active comparator | Drug: Insertion of nitroglycerin ointment |
| Placebo ointment | Placebo comparator | Drug: Insertion of placebo ointment |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- age 18-45 years,
- generally healthy,
- requesting a LNG-IUS for contraception as the primary indication
Key exclusion criteria (15 listed)
- Previous pregnancy beyond 20 weeks;
- previous IUD placement or attempted IUD placement;
- previous cervical cold knife cone (CKC) or loop electrosurgical excision procedure (LEEP);
- contraindication to LNG-IUS (including pregnancy, fibroids that distort the uterine cavity, exam consistent with PID, allergy to any component of the LNG-IUS, etc);
- concurrent use of any form of nitrate therapy or medications that interact with nitroglycerin (such as phosphodiesterase V inhibitors);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insertion of nitroglycerin ointmentNitroglycerin ointment inserted into the vagina 30-45 minutes prior to IUD insertion | Drug | Active nitroglycerin ointment |
| Insertion of placebo ointmentPlacebo ointment inserted into the vagina 30-45 minutes prior to IUD insertion | Drug | Placebo ointment |
Primary outcome
Patient-reported Pain at Passage of Insertion Device Through Cervix, as Measured on a 100 mm VAS
Time frame: 30-45 minutes after insertion of nitroglycerin ointment
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.
1 secondary outcome
Provider Ease With Intrauterine Device Insertion Measured on a 100 mm VAS
Time frame: 30-45 minutes after insertion of nitroglycerin ointment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insertion of nitroglycerin ointment in people with Contraception and Pain, run by Oregon Health and Science University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient-reported Pain at Passage of Insertion Device Through Cervix, as Measured on a 100 mm VAS (time frame: 30-45 minutes after insertion of nitroglycerin ointment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2019.