Conditions: IUD Insertion
Keywords: Pain Management IUD insertion
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 220
Healthy volunteers: yes

Brief summary:
For intrauterine device (IUD) insertion, currently there are no standardized clinical guidelines for pain management. The investigators aim to explore whether adequate pain relief is possible through self-administered, non-invasive means alone. Reducing pain associated with IUD insertion may benefit patients and providers. When patients are comfortable during their procedure, it is likely the provider can more quickly and with fewer complications perform the insertion. The investigators propose to explore the effect of a locally applied vaginal lidocaine gel in place of the standard of care pain management, no intervention, prior to IUD insertions. This is a superiority, blinded, randomized controlled trial.

Detailed description:

Arms:
arm 1: If the subject is assigned to the experimental group (vaginal lidocaine jelly):

She will be given a pre-filled vaginal inserter with 10 ml of 2% lidocaine jelly) and will be asked to insert it vaginally 20-30 minutes prior to the start of her procedure. The subject will not know if she received the active drug or a placebo. arm 2: If the subject is assigned to the control group (sterile, surgical lubricant jelly):

•She will be given a pre-filled vaginal inserter with 10 ml of surgical lubricant jelly and will be asked to insert it vaginally 20-30 minutes prior to the start of her procedure. The subject will not know if she received the active drug or a placebo.

Interventions: intervention 1: Vaginal 2% Lidocaine intervention 2: Surgical Lubricant Jelly
Intervention descriptions: intervention 1: Patient-administered vaginal Lidocaine jelly verse surgical lubricant jelly intervention 2: Patient-administered vaginal surgical lubricant jelly verse Lidocaine jelly

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
SALUD: Self-Administered Lidocaine Gel for Pain Management 
with Uterine Devices: A blinded, randomized controlled trial 
 
 
 
Jennifer Conti, MD, MS 
Klaira Lerma, MPH 
Kate Shaw, MD, MS 
Paul Blumenthal, MD, MPH 
Stanford University 
 
 
 
 
 
 
 
NCT02738203 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PROJECT SUMMARY 
 
 
1. DESCRIPTION OF THE PROJECT 
 
1.1 Rationale and objectives of the study 
 
1.1.1  Rationale 
 
Despite global efforts to decrease discomfort during surgical abortion, pain remains a 
limiting factor in where and how abortions are performed. My primary fellowship 
research project focused on utilizing a self-administered lidocaine gel to decrease pain 
with first trimester surgical abortion, and found that there was no difference in pain level 
(as measured by VAS score) at time of cervical dilation between women randomized to 
the standard paracervical block group versus the lidocaine gel only group. Given that 
pain remains a limiting barrier for other gynecologic office procedures as well, we 
decided to apply this method of analgesia to intrauterine device (IUD) insertions. 
 
For these procedures no standardized clinical guidelines for pain management exist. 
Reducing pain associated with IUD insertion may benefit patients and providers. When 
patients are comfortable during their procedure, it is likely the provider can more quickly 
and with fewer complications perform the insertion. It could also be argued these 
patients would report higher satisfaction with their procedure and provider [Kass-Wolf & 
Fisher, 2014]. To our knowledge, there is limited clinical consensus on pain 
management guidelines, demonstrating value in researching potential pain 
management solutions.   
 
We propose to explore the effect of a locally applied vaginal lidocaine gel in place of the 
standard of care pain management (i.e. paracervical block or no intervention 
respectively) prior to IUD insertions. 
 
SALUD (IUD insertion): We hypothesize that lidocaine gel is superior to placebo at 
decreasing procedural pain at a variety of time points throughout the procedure. This is 
a superiority, blinded, randomized controlled trial.  
 
If self-administered vaginal gel is acceptable and effective, it would increase options for 
pain control during abortion and other gynecologic procedures (IUD insertion). 
 
 
1.1.2  Objectives and hypotheses 
 
The objective of this study is to compare pain control at various time points during IUD 
insertions using a locally applied, patient-administered lidocaine gel as compared to 
standard of care (i.e. no pre-procedural analgesia).  
 


If a patient-administered vaginal gel is acceptable and effective, it would increase 
options for pain control during these gynecologic procedures. 
 
Hypothesis: Patients who receive 20 mL of 2% lidocaine gel self-administered 20-30 
minutes prior to IUD procedures will have pain control superior to that of a placebo gel. 
 
Primary Outcomes 
• SALUD (IUD Insertion): Pain perceived by Visual Analogue Scale (0-100 mm) at 
the time of speculum removal 
 
Secondary Outcomes 
• Pain perceived at additional time points during/after the procedure: 
o Anticipated pain: measured upon clinic intake  
o Baseline pain: upon arrival to procedure room 
o After speculum placement 
o After tenaculum placement 
 
Note: The research coordinator will stand at the head of the bed beside the patient with 
an iPad that has an enlarged VAS on it. They will ask the patient to tap somewhere 
along the VAS at these various time points to indicate their respective pain score. 
 
1.2 Previous similar studies 
 
While several previous studies have evaluated possible interventions for reducing IUD 
insertion pain, few have shown promising results. Although many providers recommend 
that patients take nonsteroidal anti-inflammatory drugs (NSAIDs) prior to the procedure, 
a 2009 Cochrane review concluded that NSAIDs are not effective at reducing pain 
during IUD insertion. The same review also concluded that the use of misoprostol to 
soften and open the cervix does not effectively reduce peri-insertional pain during 
insertion in nulliparous women, and may cause side effects. In a randomized trial, a 1% 
lidocaine paracervical block did not significantly decrease perceived pain with IUD 
insertion [Mody, 2012]. Randomized controlled trials by Allen et al. and McNicholas et 
al. examined the effect of 2% cervical lidocaine gel applied 3 minutes prior to the 
procedure. Both studies found no significant differences in pain scores with IUD 
insertion or tenaculum placement when compared with placebo. 
 
To the best of our knowledge, there is no published data that 1) rigorously examines the 
effects of a prolonged time interval between local anesthetic administration and IUD 
insertion, or 2) explores whether adequate pain relief is possible through self-
administered, non-invasive means alone.  
 
In a soon to be published study conducted at Stanford (my primary fellowship project), 
self-administration of 20 ml of 2% lidocaine gel 20-30 minutes prior to first trimester 
surgical abortion was shown to be non-inferior to a traditional paracervical lidocaine 
block as a pain control approach. Given these promising results, we propose to 


evaluate the effect of 2% lidocaine gel self-administered 20-30 minutes prior to IUD 
insertion in place of the standard of care pain management (i.e, no intervention). 
 
 
1.3 Design and methodology 
 
1.3.1  Research design and General Methodological Approach 
 
This is a superiority, blinded, randomized controlled trial of women ages 18 and older 
undergoing elective IUD insertion. We chose a superiority approach based on the most 
commonly practiced method for pain management in these procedures (no 
intervention). In this study, participants and health care professionals will be blinded 
from the intervention/study group. Standard lubricating gel has the same clear gel 
appearance as lidocaine gel and will be used to ensure blinding. Due to logistical 
barriers with needing to prepare the gel immediately prior to insertion, the research 
coordinator responsible for enrolling and randomizing participants will not be blind to the 
intervention.  
 
Participants will be recruited from Stanford Gynecology Clinic. Informed consent will be 
obtained prior to enrollment by a trained research coordinator after which, patients will 
be randomized to either group by block randomization. At the completion of the 
procedure, compensation will be given in the form of a $15 Target Gift Card or a $15 
donation to a fund that assists low-income women obtain family planning services.  
 
1.3.2  Criteria for the selection of subjects 
 
Inclusion Criteria: 
Women ages 18 and older presenting for elective IUD insertion (any type of IUD, copper 
or hormonal); at an out-patient setting at Stanford; English speaking, and ability to give 
informed consent. 
 
Exclusion Criteria: 
• Pre-operative use of misoprostol 
• Allergy to study medications (lidocaine) 
• Known uterine anomaly 
• Prior cervical surgery  
• IV conscious sedation 
 
1.3.3 Subject Recruitment and Allocation 
 
Potential participants will be identified for recruitment if scheduled for IUD insertion (regardless 
of type) at the Stanford University Gynecology Clinic. They will be approached by the research 
coordinator or study investigator and consented for the study. If enrolled, they will be 
randomized by block randomization. The research coordinator will prepare a 20ml pre-filled 
syringe with either 2% lidocaine gel or placebo, so that the physician/researcher is blinded to 
the group allocated. Participants will receive the treatment previously allocated on a rolling 
bases. The patient and provider will be blinded as to the treatment group. 


 
All patients will then receive instruction on how to properly self-insert the study medication using 
a pictorial guide as previously employed in a similar RCT at this site (SALSA).  
 
1.3.4  Description of the drugs and devices to be studied  
 
Xylocaine (lidocaine HCl) is a common local anesthetic that works by stabilizing the 
neuronal membrane by inhibiting the ionic fluxes required for the initiation and 
conduction of impulses. Local anesthetics of the amide type are thought to act within the 
sodium channels of the nerve membrane. According to the packaging insert, anesthesia 
is achieved within 5 minutes, depending on the area of application, and duration of 
anesthesia is approximately 20-30 minutes.  It is used prior to many genitourinary 
procedures involving mucus membranes including the urethra, anus, and vulva. While 
no recommended dose is known for vaginal use prior to surgical abortion, 
recommended doses are known for the following procedures: 20 ml for 
proctoscopy/anoscopy; 10 ml for female urethral anesthesia as in cystoscopy. A single 
maximum dosage for 2% Xylocaine jelly is not established [Blanco 1982], however 
Lexicomp drug information for topical lidocaine jelly cites a maximum dose of 600 mg in 
any 12-hour period. 
 
The serum toxicity of intracervical lidocaine is thought to be around 5 ug/ml [Blanco 
1982] and a study looking at serum lidocaine levels 10 minutes after paracervical 
injection of 20 ml of 1% lidocaine (200 mg total) found mean blood levels of 0.9 to 1.61 
ug/ml [McKenzie 1978].   
 
Similarly, a study investigating vaginal anesthesia with 4ml of 10% lidocaine spray 
(400mg total) 5 minutes prior to high dose intracavitary brachytherapy found a 
significant decrease in procedural pain [Chen 1998]. This study also looked at serum 
lidocaine levels at various time points following administration and found that the 400mg 
dose never reached toxic levels in participants. These data are further supported by 
non-toxic levels seen after nasopharyngeal and oropharyngeal application in the studies 
sited above. 
 
Based on this information, participants in the lidocaine gel group will self-administer 20 
ml of 2% lidocaine HCl vaginally (400 mg total) 20-30 minutes prior to the start of the 
procedure. We are allowing a window of time to account for real life clinic practice and 
possible delays. 
 
 The product: 
• XYLOCAINE® JELLY 2% (lidocaine hydrochloride) AstraZeneca 
o 20 mL (20 mg/mL) – 400mg total 
 
Control Groups: 
 
SALUD (IUD Insertion Arm): 


No Intervention Group: As an alternative to lidocaine gel, participants will receive no 
intervention for pain management for IUD insertion (standard of care), but will receive 
placebo gel (standard lubricating gel). 
 
1.3.6  Follow-up procedure 
 
There is no extended follow-up planned for this study. Subjects will complete a survey 
at the completion of the procedure asking them to give a final pain score (secondary 
outcome) and assessment of overall acceptability (likelihood to recommend procedure 
or choose this form of pain control again). Any potential procedural complications will be 
managed using typical standard of care procedures for this clinic. 
 
1.3.7  Criteria for discontinuation 
 
Subjects will be able to withdraw from the study at any point during the procedure 
should they so choose.  
 
1.3.8  Laboratory and other investigations 
 
Not-applicable. 
 
1.3.9  Data management 
 
Data management will be done using RedCap, an electronic data capture program, and 
performed by the research coordinator and primary investigator (fellow).  
 
1.3.10  Data analysis 
SAS Version 9.3 and SPSS Version 23.0 will be used for data analysis.  
Statistical Methods: 
 
• Demographic characteristics will be examined among the randomized groups 
using Fisher’s exact test 
• Median VAS pain scores will be analyzed with Student’s t-tests and non-
parametric tests, respectively 
• Linear regression may be completed in multivariate analysis to identify predictors 
of pain in an exploratory analysis  
 
1.3.11  Number of subjects and statistical power 
 
SALUD (IUD Insertion): The following power calculation accounts for continuous 
outcomes in a superiority trial 
 
n = f(α/2, β) × 2 × σ2 / (μ1 − μ2)2 
o Effect size = 15% difference in VAS [Jensen 2003, Todd 1996, 
Rowbothom 2001] 


o Mean outcome in control group: 36.7mm [Allen 2013] 
o Standard deviation of VAS = 21.7mm [Allen 2013] 
o Assuming α = 0.025, β = 0.10, 90% power 
 
SUMMARY: 200 patients are required to have a 90% chance of detecting, as significant 
at the 2.5% level, a decrease in the primary outcome measure from 36.7 in the control 
group to 21.7 in the experimental group. Accounting for drop-outs and protocol 
deviations by adding 10% to the number of participants, the total enrollment will be 220. 
 
1.3.12 Study limitations 
 
The potential limitations of this study include inability to blind the research coordinator 
given the need for preparation of the gel immediately prior to the patient’s self-insertion, 
and the fact that this is a single site out-patient clinic at a university setting, that may not 
reach as widely as is desirable for the purposes of generalizability. 
 
1.3.13 Duration of project  
 
There are currently around 50 IUD insertions performed each month at the Stanford Gynecology 
Clinic, however we are tripling our IUD access clinics starting in July, so we anticipate over 100 
IUD procedures per month. Estimating 30% enrollment, the anticipated length of the study is 7-
10 months.  
 
1.4 Project management 
 
The study coordinator and investigator will be responsible for data entry in RedCap and export 
to SAS for statistical analysis and any required data cleaning. All data cleaning is tracked when 
done in this manner decreasing data entry, transposition and cleaning errors. The study 
coordinator will be responsible for maintaining locked files containing research study consents 
and any other paper documentation created. Remaining data collection will occur via the secure 
system, RedCap, using an iPad in the clinic with the patient and provider/study coordinator. 
Weekly research meetings are held at Stanford. 
 
1.5 Links with other projects 
 
Not-applicable. 
 
1.6 Main problems anticipated 
 
We do not anticipate any issues with enrollment or integration of the study into the Stanford 
Gynecology clinic and its daily operations. To ensure this, we have received approval from the 
clinic’s manager to ensure fulltime assistance from a research coordinator.   
 
1.7 Expected outcomes of the study and dissemination of findings 
 
We hope to show that a self-inserted vaginal lidocaine is superior to the standard of care (no 
analgesia) with IUD insertion. If superior and acceptable to patient, a vaginal gel would offer an 
alternative route of pain control for an often uncomfortable procedure.  


 
1.8 References 
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Allen RH, Raker C, Goyal V. Higher dose cervical 2% lidocaine gel for IUD insertion: a 
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Belanger E, Melzack R, Lauzon P. Pain of first-trimester abortion: a study of 
psychosocial and medical predictors. Pain 1989;36:339-50. 
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Blanco L, Reid P, King T. Plasma Lidocaine Levels following Paracervical Infiltration for 
Aspiration Abortion. Obstet Gynecol 1982; 60:506-508. 
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Chen H, et al. Local vaginal anesthesia during high-dose-rate intracavitary 
brachytherapy for cervical cancer. Int. J. Radiation Oncology Biol. Phys., Vol. 42, No. 3, 
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Costello MF, Steigrad S, Collet A. A prospective, randomized, single-blinded, controlled 
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- 
Guttmacher Institute. Facts on Induced Abortion Worldwide. January 2012. 
http://www.guttmacher.org/pubs/fb_IAW.html 
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Guttmacher Institute. Facts on Induced Abortion In the United States. July 2014. 
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2.  ETHICAL CONSIDERATIONS   
 
IRB approval has been sought and approval is pending from the Stanford University Research 
Compliance Office. 
 
2.1 Informed decision & making and confidentiality 
 
Please see the attached consent form (APPENDIX A). This form will also be translated into 
Spanish. 
 
 
3.  BUDGET   
 
3.1   Line Item Budget / 3.2   Budget Justification 


 
Please see the attached line item budget (APPENDIX B).  
 
 
 
4. APPENDICES 
 
• 
Appendix A: Sample Patient Consent Form 
• 
Appendix B: Line Item Budget & Budget Justification