Vapocoolant Application for Pain Reduction During Office-based Gynecologic Procedures: a Randomized Controlled Trial (VAPOR)
Phase: PHASE4
Conditions: Pain With Paracervical Block, Pain With Gynecology Procedure, Pain
Sponsor: Queen's Medical Center

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Research Study Protocol 
 
Title: Vapocoolant Application for Pain Reduction during Office-based Gynecologic 
Procedures: a Randomized Controlled Trial (VAPOR) 
 
Principal Investigators:  
Catherine (Lule) Rault, MD, MPH 
1380 Lusitana St. POB I Suite 1004 
Honolulu, HI 96813 
crault@hawaii.edu 
808-375-3785 
 
Shandhini Raidoo, MD, MPH 
1380 Lusitana St. POB I Suite 1004 
Honolulu, HI 96813  
sraidoo@hawaii.edu 
808-375-3785 
 
Sub-Investigators:  
Reni Soon, MD, MPH 
 
 
Bliss Kaneshiro, MD, MPH 
 
 
Melissa Natavio, MD, MPH 
 
 
Mary Tschann, PhD, MPH 
 
 
Olivia Manayan, MD 
 
Other study personnel:Julianne Byun 
 
 
Jamie Kim 
 
 
Kayti Luu 
 
 
Destini Settlemyre 
 
 
Alisa White 
 
 
Kara Yoshinaga 
 
 
Natalia Fornal 
 
 
Brandi Mikami 
 
 
Riana Kawasaki 
 
 
Michelle Nguyen 
 
 
Tiffany-Ryan Kusano 
 
 
Thanes Ganesan 
 
 
Jacob Erban 
 
 
Paige Harukani 
 
 
 
 
Study Sites:  
Queen’s Medical Center POB1 Suite 1004 
 
 

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Summary/Abstract 
Section 1: Background and Objections 
1.1 Background and Rationale 
1.2 Objectives and Hypothesis 
Section 2: Criteria for Subject Selection 
2.1 Sample Size and Duration 
2.2 Study Population 
2.3 Eligibility Criteria 
Section 3: Methods and Procedures 
3.1  Overall Study Design 
3.2 Subject recruitment, admission and allocation 
3.3 Screening/Preoperative Evaluation 
3.4 Procedure Setting and Providers 
3.5 Randomization 
3.6 Allocation Concealment method 
3.7 Implementation 
3.8 Blinding 
3.9 Criteria for Discontinuation 
3.10 Standardization of Procedure 
3.11 Follow up 
3.11 Description of the intervention to be studied 
3.12 Vapocoolant Supply, Packaging, Labeling and Storage 
3.13 Data Analysis and Statistical Methods 
3.14 Data Handling and Record Keeping 
3.16  Record Retention 
3.17  Direct Access to Source Data/Documentation 
Section 4 Risks/Benefit Assessment 
4.1 Risks 
4.2 Potential Benefits 
4.3 Alternatives to participation 
4.4 Financial Obligations/Cost: 
4.5 Safety and Adverse Events 
5.  Ethical Considerations 
6.  Study Finances 
7.  Publication and Presentation Plans 
8.  Timeline 
Appendix and Attachments: 
1. Study Calendar: Proposed Project Timeline (See Below) 
2. Budget (See Below) 

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3. Roles of Personnel (See Below) 
4. Patient Consent Form (Separately Attached) 
5. Patient Demographic Intake Form (Separately Attached) 
6. Num Information - Six PDF Documents (Separately Attached) 
7. Data Collection Form- Visual Analog Scale (Separately Attached) 
8. Letter of Agreement (LOA) (Separately Attached) 
9. Grant Application Submission to Society of Family Planning (Separately Attached) 
 
 
 

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Summary/Abstract 
 
Study Title: Vapocoolant Application for Pain Reduction during Office-based Gynecologic 
Procedures: a Randomized Controlled Trial (VAPOR) 
 
Background: Gynecologic office procedures are common and painful. For office-based 
procedures, providers routinely use a lidocaine injection into the cervix, known as a paracervical 
block, to decrease pain. However, the paracervical block itself is painful. Vapocoolant spray has 
been found in other specialties to decrease pain with injections, but it has not yet been 
investigated in gynecologic procedures. Vapocoolant spray is easy to use, rapidly acting, 
inexpensive (approximately 5 dollars for a single use vial) and readily available. 
 
Objective: To determine if vapocoolant spray reduces pain associated with paracervical block. 
 
Methods/Design: We propose a randomized, placebo-controlled, single-blinded trial among 
patients receiving a paracervical block. All patients will receive ibuprofen prior to the procedure 
per current standard of care in our clinic. Vapocoolant or placebo (sterile water) will be sprayed 
on the cervix prior to administering a paracervical block. Exclusion criteria includes previous use 
of a vapocoolant prior to an injection, use of an anxiolytic, narcotic or sedation prior to the 
procedure, or contraindication to receiving ibuprofen. Our primary outcome is pain at the time of 
the paracervical block using a 100-mm visual analog scale (VAS). Secondary outcomes include 
pain at tenaculum placement, pain the remainder of the procedure, patient satisfaction, provider 
rating of ease of vapocoolant use.  
 
Outcomes: We hypothesize that the vapocoolant spray will decrease patients’ pain at the time of 
the paracervical block and tenaculum placement. We hypothesize that the vapocoolant spray will 
have no effect on pain for the remainder of the procedure. Patients who receive the vapocoolant 
will have high satisfaction and providers will find it easy to use. 
 
Sample size and population: A difference of 30% or 13-20 mm on a 100 mm pain VAS 
is  considered clinically significant[1-3]. Based on existing research, we estimate mean pain with 
paracervical block to be between 54-60mm on the VAS, with a standard deviation of 25mm [1, 
4, 5] . To detect a 30% difference in pain scores between the two groups with an alpha of 0.05 
and 80% power and accounting for 10% participant drop-out, we will recruit 98 total 
participants, with 49 participants in each group. 
 
 
 

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Section 1: Background and Objections 
1.1 Background and Rationale 
Gynecologic office procedures like IUD insertion, endometrial biopsy and first-trimester 
procedural abortion are commonly done in the United States under local anesthetic. Local 
anesthetic is safer and less expensive than moderate sedation, particularly for these very brief 
procedures; however, local anesthetic may not adequately manage pain for some patients. The 
majority (78-97%) of patients report at least moderate pain with first trimester procedural 
abortion [6]. 
 
Many providers routinely use a lidocaine injection known as a paracervical block (PCB) to 
decrease pain with first trimester procedural abortion, and occasionally with other gynecologic 
procedures such as IUD insertions and endometrial biopsies [1, 5, 6]. However, the PCB itself is 
painful. Renner et al noted PCB administration was more painful than a sham (mean 55 mm 
compared with sham 30 mm, P<.001 using a 100 mg Visual Analogue Scale (VAS) 5. Chin et al 
evaluated pain at the time of  PCB with buffered and plain lidocaine and noted median VAS 
scores for the PCB injection to be 30 (interquartile range (IQR) 15.3-64.5) for buffered lidocaine 
and and 44.5 (IQR 18.3-65) for plain lidocaine (p=0.32) 4.  
 
Before the PCB can be placed, the clinician applies a tenaculum, which is a single-toothed 
instrument that punctures the cervix so that it can be moved and stabilized during the procedure. 
Placement of the tenaculum is painful. Providers routinely place 2 ml of anesthetic via 
intracervical injection at the anterior lip of the cervix to reduce pain as the tenaculum punctures 
the cervix, which has been shown to reduce pain associated with the tenaculum, however the 
injection itself is also painful [7].  An intervention to reduce pain prior to tenaculum and PCB 
placement could reduce the pain experienced during the procedure and improve the overall 
patient experience.   
 
Vapocoolant spray consists of pentafluoropropane and tetrafluoroethane which causes the skin or 
mucosa to become cold and thereby provides analgesia [8]. Cold decreases pain through multiple 
channels, including stimulation of peripheral neural receptors, alteration of neural transmission 
velocity, deceleration of transmission of pain signal to central nervous system and distraction 
from pain [9, 10]. Vapocoolant spray is currently being used across other fields of medicine to 
decrease pain during injections, IV starts, blood draws, and nerve blocks [7, 8, 10-16]. 
Vapocoolant spray has been used in dental procedures, demonstrating safety when used on 
mucosal areas [17, 18].  
 
Vapocoolant spray is easy to use, acts rapidly and is readily available and inexpensive. A single 
use vial costs approximately $5.00 [19]. Vapocoolant spray represents a novel intervention for 
the management of pain during gynecologic procedures of any kind.  We were unable to identify 
any previous studies evaluating the use of vapocoolant spray in the vagina or on the cervix to 
reduce pain with gynecologic procedures, however existing research using vapocoolant in dental 
procedures has confirmed the safety of their use in mucosal areas [17, 18]. Therefore, we plan to 
evaluate if vapocoolant decreases pain with paracervical block insertion. The vapocoolant spray 
has a lasting effect of one minute, therefore, we hypothesize that it will reduce pain with the 

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paracervical block insertion and tenaculum placement, but we do not expect it to reduce pain 
with the abortion procedure (dilation and aspiration).  
 
Our primary outcome is to determine if vapocoolant spray reduces pain at the time of 
paracervical block placement. Our secondary outcomes are to evaluate if vapocoolant spray 
reduces pain with tenaculum placement, pain with the remainder of the procedure, patient 
satisfaction, side effects and provider’s perception of ease of use of the vapocoolant spray. 
 
The study will be conducted in compliance with the protocol approved by the Research and 
Institutional Review Committee, and according to Good Clinical Practice standards, applicable 
federal regulations, and Queen’s Medical Center (QMC) institutional policies and procedures.  
 
1.2 Objectives and Hypothesis  
Our study objective is to determine if vapocoolant spray reduces pain at the time of paracervical 
block placement.  
 
Our secondary outcomes are to evaluate if vapocoolant spray reduces pain with tenaculum 
placement, pain with dilation, pain with aspiration. We will also evaluate patient satisfaction, 
side effects and provider’s perception of ease of use of the vapocoolant spray. 
 
Before the procedure, we will collect demographic information from the patient and have the 
patients complete a baseline anxiety measure on a visual analog scale (VAS) (all data collection 
forms can be found in Appendix 5). Before, during and immediately after the procedure, we will 
use the VAS to evaluate patients' pain. We will also use the VAS immediately after the 
procedure to determine the patient’s satisfaction and the provider’s perception of ease of use of 
the vapocoolant spray (all data collection forms can be found in Appendix 5). 
Section 2: Criteria for Subject Selection 
2.1 Sample Size and Duration 
A difference of 30% or 13-20 mm on a 100 mm pain VAS is considered clinically significant [1-
3]. Based on existing research, we estimate mean pain with paracervical block to be between 54-
60mm on the VAS, with a standard deviation of 25mm [1, 4, 5]. To detect a 30% difference in 
pain scores between the two groups with an alpha of 0.05 and 80% power and accounting for 
10% participant drop-out, we will recruit 98 total participants, with 49 participants in each group. 
 
For a sample size of 98, we estimate participant enrollment to take 6 - 15 months. Chin 2020 
evaluated lidocaine v buffered lidocaine for paracervical block for patients undergoing outpatient 
uterine aspiration of a first-trimester pregnancy or an early pregnancy loss. Chin 2020 study was 
performed with this same physician group in their prior practice location, which had nearly 
identical set-up and patient flow as the Queen's POB1 office. That study took 15 months for 
participant enrollment. Currently, at our clinic, we do about eight procedures requiring 
paracervical block per week. Assuming a 50% enrollment rate, enrollment would take about 6 
months. Based on these two data points, we estimate between 6-15 months for enrollment. 

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2.2 Study Population 
The study population will consist of patients who are having a procedure requiring a paracervical 
block. This study will be conducted at The Queen’s Medical Center POB1 Clinic 1004. 
 
2.3 Eligibility Criteria 
 
Inclusion Criteria 
o Age 18 years of age or older 
o Undergoing a procedure requiring paracervical block in the Queens’s POB1 Suite 
1004 office (e.g. abortion <13weeks 6days, IUD insertion, laminaria placement) 
o English-speaking 
o Able and willing to sign the informed consent form and agree to terms of the 
study 
 
Exclusion Criteria 
o Required or requested narcotics, anxiolytics, IV sedation, or general anesthesia 
for the procedure  
o Declines or has a contraindication/allergy to ibuprofen  
o Previously received vapocoolant spray in a medical setting  
o Contraindications or allergies to lidocaine for paracervical block or vapocoolant 
spray components (1,1,3,3-pentafluoropropaine or 1,1,1,2-tetrafluroethane) 
 
Of note, the manufacturer does state not for use in diabetic patients or patients with poor 
circulation. This is due to cooling/freezing effects on areas with poor vascularization like 
fingers. As the cervix is well perfused, we believe it is safe to use the vapocoolant spray 
on diabetics.  
 
 
 

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Section 3: Methods and Procedures 
 
3.1  Overall Study Design 
 
Prospective, Single Blind, Randomized, Placebo Controlled Trial study of patients 
receiving paracervical block for a gynecologic procedure  
 
This prospective randomized control trial will consist of two study arms. As participants 
are enrolled they will randomly be assigned to Arm 1, vapocoolant spray, or to Arm 2, 
normal saline placebo spray.  
 
Allocation 1:1 

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 
Participants will be randomized to receive Num Vapocoolant Spray versus Nature’s 
Tears Spray Placebo (Sterile water).  
 
Settings and locations 
o  Queen’s Medical Center POB1 Suite 1004 
 
3.2 Subject recruitment, admission and allocation  
Potential participants will be  patients having a gynecologic procedure requiring a paracervical 
block at POB1 Suite 1004. If a patient in the clinic decides to undergo a procedure which 
requires a paracervical block, the patient will first receive standard counseling for that procedure 
and complete informed consent for that procedure. All these steps will be completed prior to the 
patient being informed of their potential eligibility for the research study.  
 The doctor will then evaluate if the patient meets inclusion/exclusion criteria for this 
study. If patient is a candidate for the study, the OBGYN resident/CFP Fellow/Attending 
will approach the patient about being in the study and consent the patient if they  desire to 
participate in the study,  
 The  patient receive their pre-procedure medications (ibuprofen 600 mg and whatever 
other medications are required for the specific procedure the patient is having). After the 
ibuprofen 600 mg is given, the patient waits 10 minutes to 4 hours before the procedure 
to ensure the medications are working for the procedure.  
 During this 10 minute-4 hour wait period, the research coordinator will introduce 
themselves to the patient to complete the Data Collection sheet.  
 
The research coordinator will be present to the room for the procedure.  
 
Allocation: if a patient opts to participate in the study, they will be randomly assigned to either 
vapocoolant spray or placebo spray. They will be assigned by the doctor picking the next 
concealed envelope.  
 
3.3 Screening/Preoperative Evaluation 
Potential participants will be identified at their office visits at POB1 Suite 1004 at The Queen’s 
Medical Center.  If a patient in the clinic decides to undergo a procedure which requires a 
paracervical block, the patient will be first consented for their procedure. Then OBGYN 
resident/CFP fellow/attending will evaluate if the patient meets inclusion/exclusion criteria for 
this study. The doctor will directly ask the patient is she has taken anxiolytic that day, desires an 
anxiolytic for the procedure, taken a narcotic or other sedative that day, if the patient has any 
medical condition that forbids them from taking ibuprofen, if the patient does not desire 
ibuprofen, if the patient has used vapocoolant spray previously.  
 
Based on the answers to these above questions,  the patient’s eligibility for our study will be 
determined. Provider will inform the patient they are eligible for a research study and ask if they 
are interested in learning more about the study. If they opt to hear more, study physician will 
meet with the patient and complete the consent process.  
 

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It will be made clear to all patients that their decision to enroll or not enroll in the study will not 
affect their access to requested abortion care , their post-procedural care, and their relationship 
with their physician or QMC.   Consent for the study will be obtained by study investigators 
and/or physicians following the informed consent standard operating procedure. After 
enrollment, a copy of the study consent will be given to the subject (see Consent Form 
attachment). At this time, participants will also receive $50 remuneration for their participation 
in the study via a gift card.  
 
 
3.4 Procedure Setting and Providers 
At The Queen’s Medical Center POB1 Suite 1004 office, one of four complex family planning 
trained providers (all listed as study co-investigators) will perform all procedures. Fellows and 
residents may participate in the procedure under direct supervision. In study documents, we will 
record the name of the attending and if residents or fellows participated in the procedure. 
 
All patients will received standard of care for the procedure they have consented to that requires 
a paracervical block. In terms of the research, the patient will receive standard of care + a spray 
after speculum placement. The spray being either the vapocoolant spray or placebo Nature’s 
Tears. All other aspects of the procedure will remain the same.  
 
Study team will collect pertinent demographic and medical history information (as indicated in 
the data collection form) directly from the patient prior to the procedure during the 10 min-4hour 
wait after taking ibuprofen. Physician-investigators 
will be asked their opinion on ease-of-use of the vapocoolant after each procedure. 
3.5 Randomization and Allocation Concealment 
Prior to the start of the study, an individual not involved with the conduct of the study will 
determine allocation of subjects by computer-generated random numbers in block sizes to be 
determined by that individual. This individual will then place allocation assignment cards in 
sequentially numbered, sealed, opaque envelopes containing study group assignments which will 
be opened on the day of the procedure by the doctor performing the procedure.  
 
The envelopes will be kept in the clinic. After a patient has chosen to participate in the study, the 
doctor performing the procedure, will pick the next numerical, sealed, opaque envelope. The 
doctor will open the envelop and see if the patient will be receiving the vapocoolant spray or the 
placebo spray. The doctor will then get the correct spray from the cabinet, which will be stored 
in the clinic. The doctor will wrap the spray in a blue towel and place on the tray for the 
procedure under the blue sterility drap of the instruments. Once in the room, the doctor will place 
the spray still wrapped in the blue towl in the drawer between the patients legs. This prohibits 
anyone from seeing the spray besides the doctors. 
 
The patient will be blinded to what spray they receive. 
 
Investigators will assign each subject a study identification number in sequential order.   

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3.7 Implementation 
A research assistant, unaware of the study allocation, will stand at the head of the bed to collect 
data from the patient during the procedure. The provider will ensure that the spray used is not 
visible to the participant or the research assistant throughout the data collection period. The spray 
will be placed in the drawer between the patient’s legs, only visible to the doctor performing the 
procedure.  
 
3.8 Blinding 
The participants and the research assistants collecting data from the participant during the 
procedure will be blinded to study allocation. 
 
The providers performing the procedure will not be blinded. In prior research conducted with 
vapocoolant, the studies were designed to be double blinded, however through personal 
communication with those studies’, Dr. Mace, we learned that to provide blinding was almost 
impossible. Even with identical packaging, the providers could determine which product was 
being applied because the vapocoolant is cold on the provider's hand when they spray and turns 
the skin white, while the normal saline drips on contact with the skin [11, 12]. Based on this, we 
determined we would not be able to blind providers to study group allocation and have used 
other techniques (described below) to reduce the potential bias this lack of blinding may 
introduce. 
 
3.9 Criteria for Discontinuation 
Participants may end study participation upon request at any point in the study. After study 
consent and randomization but prior to the procedure, patients may be discontinued from study 
participation if the provider deems it necessary, the patient chooses to discontinue, or if 
exclusion criteria are newly identified.  
 
We will follow intention-to-treat principles and analyze all data based on its allocation regardless 
of whether or not the intervention was received.  
 
3.10 Standardization of Procedure 
Preprocedural counseling and evaluation are consistent with clinic protocols. All participants will 
receive premedication of 600 mg oral ibuprofen before (10 minutes to 4 hours) the procedure.  
 
All patients who consent to the study will receive standard counseling prior to their procedure. 
The provider will wear a face mask during the procedure as is standard of care. The procedure 
will start with a bimanual exam by the provider. Next, the provider will place a speculum. At this 

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point, participants assigned to Arm 1 will receive vapocoolant spray (treatment), while 
participants assigned to Arm 2 will receive normal saline spray (placebo). 
 
The vapocoolant spray is a single-use spray bottle containing (8.5 grams) vapocoolant spray. 
Providers will follow the manufacturer's brochure for the vapocoolant application (Appendix 
6.1). To use the spray, the provider will twist to break the tamper evident label, pull off the base 
cap, and then pull off the sterile barrier tab on the nozzle. From 3-6 inches away, the provider 
will spray the cervix for 4-6 seconds until the cervix turns white. The Num vapocoolant spray 
has a cooling effect of 1 minute ([19], Appendix 6.1)  
 
We will plan to use Nature’s Tears for placebo in the same method, spraying from 3-6 inches 
away from the cervix for 4-6 seconds.  
 
Clinicians will all be trained to use both the Num vapocoolant spray and Nature’s Tear prior to 
first study patient encounter. Additional supplies will be purchased to allow for all doctors 
involved in the study to practice consistent use of the device following the Num Vapocoolant 
Application Guide (Appendix 6). Natures Tears is a standard spray can. The provider simply 
needs to hold down the nozzle. To ensure standardization between the two groups, the provider 
will also spray the cervix with Natures Tear from 3-6 inches away and for 4-6 seconds.  
 
Both sprays are to be aimed at the cervix, however, some of the spray may come in contact with 
the vaginal sidewall. The bivalve speculum will protect the anterior and posterior vagina, but the 
side walls could have collateral effects of feeling the spray.  
 
There is potential for the doctor performing the procedure to inhale the spray. To decrease this 
risk, the providers will be wearing a face mask and be gloved as is standard of care.  
 
After the treatment or placebo spray is administered, the provider will then immediately follow a 
standardized protocol for administering the paracervical block based on existing research on 
tenaculum placement and paracervical block best practices [1, 4, 20] 
 
Paracervical Block Standard Administration:  The providers will inject two ml at the tenaculum 
site, 12 o'clock superficially into the cervix. The provider will then place the tenaculum, using a 
standardized “slow” placement of  the tenaculum (e.g. counting to 10 while placing the 
tenaculum). 
 
Prior to the procedure, as is standard office protocol, the MA will prepare a syringe loaded with 
20 ml of 0.5% lidocaine, 20 gauge spinal needle. The providers will inject the remaining 18 mL 
slowly over 60 seconds into the cervicovaginal junction in two equal aliquots at 4 and 8 o'clock 
1. We will perform a continuous injection from superficial to deep (3cm) to superficial (injection 
with insertion and withdrawal) 
 
The providers will standardize language during the PCB application to reduce bias or priming of 
the patient. Each provider will use the following language: “You may or may not feel a sharp 
pinch as I am injecting numbing medicine”. This will be repeated as necessary throughout 
injection of the paracervical at 4 and 8 o'clock 1. 

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During the procedure, the research assistant will ask the patient to verbally report their level of 
pain based on the 100 mm visual analog scale (VAS) at the following points of the procedure: 
1. Prior to the start of the procedure (baseline) 
2. After tenaculum placement 
3. After paracervical block 
4. After gynecologic procedure complete  
5. Five minutes post-procedure 
6. Post procedure: Physician Ease of Use 
 
Post Procedure evaluation  
After the procedure, which is usually about 10 minutes, the provider will immediately evaluate 
the vagina and cervix as is standard of care. Besides evaluating for bleeding, the provider will 
also evaluate for any side effects from the vapocoolant/placebo, including second and third 
degrees burns, cryogenic injury, failure of the cannister, bruising, blistering, bleeding, 
pain, blister, cryogenic burn, infection, discharge. 
 
Physician Ease of Use 
We will submit waiver of consent for provider physician investigators to collect their evaluation of 
ease of use for each subject. We anticipate ease of use will be uniform, but perhaps the ease of 
use will vary based on patient characteristics, which is why we want to ask the question for each 
subject. Collection of such data is considered standard in our field whenever a new pain 
management technique is evaluated.  
 
 
3.11 Follow up 
One to two days after the procedure, one of the study investigators will text and/or call the 
patient to see if they have any concerns or concerning symptoms. If the patient does report 
concerning symptoms and need for evaluation, the patient will be scheduled for an appointment 
as soon as possible back in the clinic for a physical exam (pelvic exam to evaluate the 
vagina/cervix, if necessary).  
3.11 Description of the intervention to be studied 
Num is a sterile vapocoolant topical anesthetic spray used to numb the skin prior to needle 
procedures. It is made by 623 Medical in Morrisville, NC.  
3.12 Vapocoolant Supply, Packaging, Labeling and Storage 
Num (Vapocoolant Spray) is not currently stocked by the QMC Pharmacy. We will order it as 
part of the research study and have it stocked in our clinic. Num can be ordered in cases of 50 
units. We plan to order 1-2 cases over the course of the study – as our planned project is a 
sample size of 49 participants in the treatment group. The Num product is temperature sensitive 

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and needs to be stored in an environment <140 Degree Fahrenheit. Our clinic has central air 
conditioning and is usually between 65-85 Degrees Fahrenheit. Num has a shelf life of 3 years.  
 
The placebo (Nature's Tears) is not currently stocked by the QMC Pharmacy. Will will also 
order this medication and have it stocked in our clinic. We plan to order about 50 units and keep 
them in our clinic with the Num product. Nature’s Tears has a shelf life of 5 years. 
3.13 Data Analysis and Statistical Methods 
We will assess the primary objective by comparing the mean  pain score after paracervical block 
injection from participants receiving vapocoolant spray versus normal saline. If VAS scores are 
normally distributed, we will report means as primary outcomes and use student’s t-test to 
compare groups. If VAS scores are non-normally distributed, we will report median scores as 
primary outcome and use nonparametric testing (i.e. Mann Whitney U test) to compare the two 
groups.  
 
Secondary Outcomes: 
 
Patient pre procedure anxiety – VAS 
 
Patient pre procedure pain score – VAS 
 
Pain with tenaculum placement – VAS 
 
Pain with procedure- VAS – 
 
Pain 5 minutes after procedure – VAS 
 
Satisfaction with pain control during procedure – VAS 
 
Satisfaction with procedure – VAS 
 
Provider ease of use of product – VAS 
 
We will also use the Student T-test or Mann Whitney U test to assess our secondary objectives 
by comparing mean/median difference in pain during other time points in the procedure and 
overall satisfaction with pain.  
 
No interim analysis is planned. Dr. Rault and Dr. Raidoo will be responsible for protecting and 
monitoring the rights, safety and welfare of the subjects and can perform an interim analysis if it 
is deemed necessary for determining the safety of continuing the trial. If more than 5 participants 
note side effects at the 1-2 day text/phone call follow up, we will perform an interim 
analysis.  Statistical analysis will be performed with either Excel or SPSS .  Data will be 
analyzed using intention to treat principles. 
3.14 Data Handling and Record Keeping   
Only the primary investigators and research assistants will have access to study records, which 
will be kept in locked file cabinets in the study investigator’s office.  Each participant will be 
assigned a unique study ID. We will create a coded database using these study IDs but 
containing no PHI for analysis, which will be stored on an encrypted and password protected 
computer in the research office. The codebook linking participant identifiers to StudyID will be 
stored in a password protected, secure database accessible only to the study team. Any 
publications or presentations will be reported without reporting any personal health 
identifiers.  Any deviations from the planned statistical analysis will be documented. 

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3.15  Confidentiality and Data Security 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  Those regulations require a signed subject authorization informing the subject of the 
following: 
 
What protected health information (PHI) will be collected from subjects in this study 
 
Who will have access to that information and why 
 
Who will use or disclose that information 
 
The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at 
the end of their scheduled study period.” 
 
Hard copies of clinical information and data will always be kept in a secured place in our 
research offices, and only study team members will be able to access them on an as-needed 
basis.  Key personnel may not alter the data in any database without specific cause and approval 
of the Investigator.  For de-identification, all subjects will be assigned a unique study ID number 
when they enter the study.  Data will be recorded on the paper data collection form and 
converted into an electronic file database, such as REDCap or Excel.  Study databases will be 
password protected, and all portable devices will be fully encrypted.  No data will be sent over 
the Internet unless it is de-identified. Data will be de-identified prior to any analysis.  We will 
keep codes linking the study identification number with the name of the subject confidential, 
secured by password-protected data file within the locked research unit of the Principal 
Investigators. Further measures to ensure data security will adhere to security standards set by 
the Queen’s Medical Center and the RIRC. 
 
 
3.16  Record Retention 
Study documents will be retained for at least three years after the formal discontinuation of this 
project.  They will be stored in locked, secured cabinets in the PI’s office.  All data will be de-
identified.  Any electronic files will be password protected and encrypted.  If the Primary 
Investigator leaves Hawaii, she will make arrangements to destroy the data at the designated 
time.   
 
3.17  Direct Access to Source Data/Documentation 

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The investigators will permit study-related monitoring, audits, RIRC review, and regulatory 
inspections/audits by providing direct access to all study related data/documents.  This will be 
indicated in the consent process with the potential subjects. 
 
Section 4 Risks/Benefit Assessment 
 
4.1 Risks 
This study presents with risks from the use of vapocoolant spray. Vapocoolant spray has adverse 
side effects, such as irritation, thermal burn, cryogenic injury, bruising, blistering, bleeding, 
pain, thawing process may be painful, infection, discharge and delayed healing.  
All patients will receive the standard of care for their paracervical block procedure, with the 
addition of either a numbing vapocoolant agent or placebo. Previous studies evaluating 
vapocoolant spray have shown that patients tolerate it well on skin or on mucosa in dental 
procedures [17, 18].  
 
4.2 Potential Benefits 
Our hypothesis is that subjects who participate in this study will likely benefit from the 
vapocoolant spray by having decreased pain with the paracervical block. There is a possibility 
they will experience no benefit.  This study could help  patients having in office first trimester 
abortions in the future have less pain..  
 
4.3 Alternatives to participation 
If a participant decides to withdraw from the study, the patient will receive our standard of care 
for the procedure, without either vapocoolant spray or normal saline spray. 
 
4.4 Financial Obligations/Cost: 
Participants will not be billed for the vapocoolant or placebo. All standard of care labs, 
medications and procedures for the gynecologic procedure will be billed through the subject's 
insurance, if they plan to use insurance, or at patient’s own expense. There will be no 
compensation offered for injury or adverse events of this study.  
4.5 Safety and Adverse Events 
The principal investigators, Dr. Rault and Dr. Raidoo, will be primarily responsible for 
protecting and monitoring the rights, safety and welfare of the subjects.  They will meet regularly 

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(i.e. weekly or bimonthly depending on subject enrollment) with the research coordinators to 
monitor data quality.   
We will monitor if there are adverse side effects from the vapocoolant spray noted by the 
physician during the immediate post procedural evaluation of the vagina or cervix or by the 
patient at the follow up text/phone call encounter 1-2 days post procedure. If patients encounter 
concerning symptoms/side effects 1-2 days post procedure, we will schedule the patient for an in 
person visit as soon as possible to evaluate concerns with a physical exam (pelvic exam if 
necessary). 
 
5.  Ethical Considerations 
This study will be conducted according to US and international standards of Good Clinical 
Practice, applicable government regulations and institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to The Queen’s Medical Center Research 
and Institutional Review Committee (RIRC) for formal approval to conduct the study.  The 
decision of the RIRC concerning the conduct of the study will be made in writing to the 
investigator and a copy of this decision will be provided to the sponsor before commencement of 
this study. 
 
All subjects for this study will be provided an informed consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study.  This consent form will be submitted with the protocol for review and 
approval by the RIRC for the study.  The formal consent of a subject, using the RIRC-approved 
consent form, must be obtained before the subject enters the study.  This consent form must be 
signed by the subject or legally acceptable surrogate, and the investigator-designated research 
professional obtaining consent. 
6.  Study Finances 
Study funds from this project are through a grant from the Society of Family Planning 
(application pending). These funds will go towards salaries of staff and paying for the 
vapocoolant/placebo. (see Appendix 2 – Budget for more information).  
7.  Publication and Presentation Plans 
Findings from this study will be disseminated by multiple means.  Results will be presented at 
the Annual Society of Family Planning Meeting in 2025.  We plan to present at a national 
meeting such as the American College of Obstetricians and Gynecologists or the Annual 
National Abortion Federation Meeting.  This study will be submitted for publication to a 
nationally recognized peer-reviewed journal such as Obstetrics & Gynecology, Contraception, or 
the American Journal of Obstetrics & Gynecology.   
8.  Timeline   

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After IRB approval is granted, we anticipate completing recruitment and enrollment in about 18 
months with data analysis to occur within a month after completion of enrollment. Please see 
attached study timeline. 
 
 
 
 
 
 
Appendix and Attachments: 
1. Study Calendar: Proposed Project Timeline (See Below) 
2. Budget (See Below) 
3. Roles of Personnel (See Below) 
4. VAPOR Patient Consent Form (Separately Attached) 
5. Data Collection Form - Patient Demographic Form and Visual Analog Scale (Separately 
Attached) 
6. Num Information - Seven PDF Documents (Separately Attached) 
7. Letter of Agreement (LOA) (Separately Attached) 
8. Email Correspondence with Written Financial Support through Lakshmi Devi and 
Devraj Sharma Endowment 
 
 
 

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Appendix 1.  
Study Calendar (Proposed Project Timeline) 
 
Year 1 
Oct-
23 
Nov-
23 
Dec-
23 
Jan-
24 
Feb-
24 
Mar-
24 
Apr-
24 
May-
24 
Jun-
24 
Jul-
24 
Aug-
24 
Sep-
24 
Study 
Development 
x 
x 
x 
x 
  
  
  
  
  
  
  
  
Consent material 
development 
x 
x 
x 
x 
  
  
  
  
  
  
  
  
Institutional 
human subjects 
review 
x 
x 
x 
x 
  
  
  
  
  
  
  
  
Study Activities 
Staff training 
  
  
x 
x 
x 
  
  
  
  
  
  
  
Database 
development 
  
  
x 
x 
x 
  
  
  
  
  
  
  
Subject 
recruitment 
  
  
  
x 
x 
  
  
  
  
  
  
  
Data Collection 
  
  
  
x 
x 
x 
x 
x 
x 
x 
x 
x 
Data entry 
  
  
  
  
x 
x 
x 
x 
x 
x 
x 
x 
Year 2 
Oct-
24 
Nov-
24 
Dec-
24 
Jan-
25 
Feb-
25 
Mar-
25 
Apr-
25 
May-
25 
Jun-
25 
  
  
  
Data Collection 
x 
x 
x 
x 
x 
x 
x 
  
  
  
  
  
Data entry 
x 
x 
x 
x 
x 
x 
x 
x 
  
  
  
  
Data Analysis 
Data cleaning 
  
  
  
  
  
  
x 
x 
x 
  
  
  
Data analysis 
  
  
  
  
  
  
x 
x 
x 
  
  
  
Final report and 
manuscript 
writing 
  
  
  
  
  
  
x 
x 
x 
  
  
  
 
 
 

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Appendix 2. Budget 
 
DETAILED BUDGET AND BUDGET JUSTIFICATION 
Study Title: VAPOR: Vapocoolant Application for Pain Reduction during 
Office-based First-trimester Abortions: a Randomized Controlled Trial 
PI Name: Catherine Rault 
Institution: The Queen’s Medical Center 
Project Start and End Dates: 10/31/2023 to 6/1/2025 
A. MATERIALS, SUPPLIES, AND OTHER EXPENSES 
  
Quantity 
Cost/Unit 
 Total 
Cost  
Num Vapocoolant (individual use) 
49 
$5.00 $245 
Placebo (Nature’s Tears Sterile Water, individual 
use) 
49  
$4.31 $212 
Participant remuneration 
98 
$50 $4,900 
  
Total Materials, Supplies, and 
Other Expenses 
$5,357 
  
TOTAL BUDGETED 
AMOUNT 
$5,357 
 
Part A. Personnel Costs 
Note: Dr. Rault’s study will be supported by the following contributions from the Family 
Planning Research Center and the University of Hawaii, Division of Family Planning: 
 
Drs. Reni Soon, Bliss Kaneshiro, Shandhini Raidoo, and Mary Tschann will provide 
ongoing guidance and consultation in the implementation, analysis, and dissemination of 
Dr. Rault’s study. 
 
The Family Planning Research Center of Hawaii will contribute the support of its full-
time research coordinators throughout the implementation of the study, including 
assistance with participant recruitment, data collection, IRB and regulatory compliance, 
and data cleaning.  
  
Part B. Materials, Supplies, and Other Expenses 
 
The Vapocoolant product (Num @ $5 per unit) for the 49 participants in the treatment 
arm 

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 
The placebo product (Nature’s Tears sterile water spray @ $4.31 per unit) for the 49 
participants in the treatment arm 
 
$50 remuneration per participant for study participation 
 
 
 
 

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Appendix 3. Roles of Personnel 
 
Lule Rault, MD, MPH (Principal Investigator): is an obstetrician-gynecologist who is currently 
completing a fellowship in Family Planning. She will be involved in all facets of the study 
including abortion care to the participants enrolled. 
 
Shandhini Raidoo, MD, MPH (Mentor, Principle Investigator) is a board-certified obstetrician-
gynecologist who specializes in Family Planning and has completed a fellowship in Family 
Planning. She is an Assistant Professor in the UH Department of Obstetrics and Gynecology and 
will provide abortion care to subjects in this study. 
 
Bliss Kaneshiro, MD, MPH: is a board-certified obstetrician-gynecologist who specializes in 
Family Planning and has completed a fellowship in Family Planning. She is a Professor in the 
UH Department of Obstetrics, Gynecology and Women’s Health and Program Director for the 
Family Planning Fellowship. Dr. Kaneshiro has extensive research experience and has conducted 
several randomized controlled trials. As Program Director, she is involved in all aspects of Dr. 
Rault’s training including her research training. Dr. Kaneshiro will be involved in all facets of 
the study including abortion care to the participants enrolled. 
 
Reni Soon, MD, MPH (Fellowship Program Director): is a board-certified obstetrician 
gynecologist who specializes in Family Planning and has completed a fellowship in Family 
Planning. She is a Professor in the UH Department of Obstetrics, Gynecology and Women’s 
Health and Program Director for the Family Planning Fellowship. As Program Director, she is 
involved in all aspects of Dr. Rault’s training including her research training. Dr. Soon will be 
involved in all facets of the study including abortion care to the participants enrolled. 
 
Melissa Faith Natavio, MD, MPH is a board-certified obstetrician-gynecologist who specializes 
in Family Planning and has completed a fellowship in Family Planning. She is an Associate 
Clinical Professor in the UH Department of Obstetrics and Gynecology and will provide abortion 
care to subjects in this study. 
 
Olivia Manayan, MD is a physician completing fellowship in complex family planning. She will 
provide abortion care to subjects in this study.  
 
Mary Tschann, PhD, MPH is a scientist at the Queen’s Medical Center department of Women’s 
Health. She will provide assistance in planning and implementation of this study, data analysis 
and manuscript development.  
 
Julianne Byun, is an ob-gyn resident rotating through Complex Family Planning rotation.  
 
Jonah Hu, has QMC is an ob-gyn resident rotating through Complex Family Planning rotation.  
 
Jamie Kim is an ob-gyn resident rotating through Complex Family Planning rotation.  
 
Kayti Luu is an ob-gyn resident rotating through Complex Family Planning rotation.  
 

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Destinie Settlemyre, is an ob-gyn resident rotating through Complex Family Planning rotation.  
 
Alisa White, is an ob-gyn resident rotating through Complex Family Planning rotation.  
 
Kara Yoshinaga, is an ob-gyn resident rotating through Complex Family Planning rotation.  
 
Natalia Fornal, is the Complex Family Planning Division’s Research Associate. She will assist 
with study enrollment, participant consenting, data collection, data management and regulatory 
requirements.  
 
Brandi Mikami, is JABSOM medical student. She will assist with enrollment, consenting, and 
data collection. 
 
Riana Kawasaki, has QMC Research Allied Health Privileges. She will assist with enrollment, 
consenting, and data collection. 
 
Michelle Nguyen, has QMC Research Allied Health Privileges. She will assist with enrollment, 
consenting, and data collection. 
 
Tiffany-Ryan Kusano, has QMC Research Allied Health Privileges. She will assist with 
enrollment, consenting, and data collection. 
 
Thanes Ganesan is a member of the CFP Division research team, he will assist with enrollment, 
consenting, and data collection. 
 
Jacob Erban, is a member of the CFP division research team. He will assist with enrollment, 
consenting, and data collection. 
 
Paige Harukani is a JABSOM medical student.  She will assist with enrollment, consenting, and 
data collection. 
 
 
 
 
  
 
 
 

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