Clinical trial NCT05251337
Conditions: Anxiety Chemotherapy-induced Nausea and Vomiting
Keywords: stem cell transplant anxiety chemotherapy-induced nausea and vomiting aromatherapy
Sponsor: Indiana University
Start date: 2022-03-07; Completion date: 2023-06-22
Enrollment: 92 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the effect of inhaled aromatherapy on symptoms of nausea/vomiting and anxiety in patients who have received a stem cell transplant. Aromatherapy involves essential oils from aromatic plants that can be absorbed into the body in different ways. Our study will be using inhaled aromatherapy, which has been found helpful for symptoms such as nausea/vomiting and anxiety.

Detailed description:
The purpose of this study is to evaluate the efficacy of aromatherapy on symptoms of chemotherapy-induced nausea, vomiting, and retching (CINVR) and anxiety for patients hospitalized for hematopoietic stem cell transplant. The primary aim will be to evaluate the effect of inhaled aromatherapy on CINVR and anxiety symptoms compared to control for 48 hours. Secondary aims include (1) Evaluating patient satisfaction with aromatherapy at completion of study; (2) Evaluating the antiemetic administration between intervention and control groups during the 48-hour intervention time span; (3) Evaluating the number and incidence of unit falls pre and post intervention.

This study will be a randomized controlled trial. Prior to randomization, participants will be asked which symptom, nausea/vomiting or anxiety, is most burdensome for them. Participants will be stratified based on their identified symptom of burden (nausea/vomiting or anxiety) and will then be randomized to either the intervention or control group, with a target of 50 participants in the nausea/vomiting symptom group (25 intervention and 25 control) and 50 participants in the anxiety symptom group (25 intervention and 25 control). Intervention and control groups will receive Wyndmere Naturals, Inc. aromatherapy patches and a symptom diary. Participants in the intervention group indicating that nausea/vomiting is the primary symptom of concern will receive peppermint inhaled aromatherapy patches (or mandarin if peppermint intolerance indicted). Participants in the intervention group indicating that anxiety is the primary symptoms of concern with receive lavender inhaled aromatherapy patches. The control group will receive non-scented aromatherapy patches (i.e., blank hydrogel adhesive patches without essential oil infusion), so it will not be feasible to blind participants to group assignment. The control group will have the same interactions with the study team as the intervention group and will complete patch changes and a symptom diary to serve as an attention control.

Arms: arm 1: Patients indicating that nausea/vomiting is their primary symptom of concern and are randomized to receive intervention will be allocated to the intervention - nausea/vomiting arm. This arm will receive peppermint inhaled aromatherapy patches (or mandarin as an alternative if they have a peppermint sensitivity). arm 2: Patients indicating that anxiety is their primary symptom of concern and are randomized to receive intervention will be allocated to the intervention - anxiety arm. This arm will receive lavender inhaled aromatherapy patches. arm 3: Patients indicating that nausea/vomiting is their primary symptom of concern and are randomized to receive control will be allocated to the control - nausea/vomiting arm. This arm will receive blank (no essential oil infusion) aromatherapy patches. arm 4: Patients indicating that anxiety is their primary symptom of concern and are randomized to receive control will be allocated to the control - anxiety arm. This arm will receive blank (no essential oil infusion) aromatherapy patches.
Interventions: intervention 1: Essential oils intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive Wyndmere Naturals, Inc. aromatherapy patches. The hydrogel adhesive patches are infused with essential oil for inhaled aromatherapy treatment. The aromatherapy patches provide an occlusive barrier that is hypoallergenic, allowing essential oils to be inhaled without coming in direct contact with the skin. Participants indicating nausea/vomiting is their symptom of concern will receive peppermint aromatherapy patches (or mandarin if peppermint sensitivity). Participants indicating anxiety is their symptom of concern will receive lavender aromatherapy patches. intervention 2: Patients assigned to either control group (nausea/vomiting or anxiety) will receive Wyndmere Naturals non-scented patches (i.e., blank hydrogel adhesive patches without essential oil infusion).

Protocol documents:
Prot_SAP_001.pdf: 
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Use of Aromatherapy to Reduce Symptom Burden in Patients 
Receiving Stem Cell Transplantation 
 
 
NCT05251337 
 
Document Date: 8.8.2023 
 
 
Monica Bates, BSN, RN, BMTCN, OCN 
Indiana University Health, Adult Academic Health Center 
550 University Blvd, Room 5252 
Indianapolis, IN 46202 
 
Alexandra Thullen, MSN, RN, AGCNS-BC, BMTCN 
Lindsay Syswerda, BS 
Michelle Bailey BCTMB, CMT 
Laura Basham MSN, RN, AGCNS-BC 
Alyson Keen MSN, RN, ACNS-BC 
 
 
 
 
 
 
 


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Table of Contents:  
Study Schema 
1. Background & Rationale 
2. Objective(s) 
1. Primary Objective 
2. Secondary Objective 
3. Tertiary/Exploratory/Correlative Objectives 
3. Outcome Measures 
1. Primary Outcome Measures 
2. Secondary Outcome Measures 
3. Tertiary/ Exploratory/ Correlative Outcome Measures 
4. Eligibility Criteria 
1. Inclusion Criteria 
2. Exclusion Criteria 
5. Study Design 
6. Enrollment/Randomization 
7. Study Procedures 
8. Study Calendar 
9. Reportable Events 
10.Data Safety Monitoring 
11.Study Withdrawal/Discontinuation 
12.Statistical Considerations 
13.Data Management 
14.Privacy/Confidentiality Issues 
15.Follow-up and Record Retention 
16.References 
17.Appendix 
 
 
1.0 
Background & Rationale 
 
Symptom burden is a challenge for patients receiving chemotherapy, with nausea/vomiting and 
anxiety being some of the most common symptoms causing distress. In particular, the burden 
experience by patients receiving hematopoietic stem cell transplant (HSCT) may far exceed 
symptom burden experienced by the general oncology population due to extremely high doses 
of chemotherapy. Hematopoietic stem cell transplant (HSCT), also call bone marrow transplant, 
is the process of infusing healthy stem cells into the human body to replace damaged cells 
caused by disease or cancer (“Stem Cell Transplantation”, n.d.). Prior to receiving a HSCT, 
patients must receive high doses of chemotherapy and/or radiation in order to help decrease the 
amount of damaged or cancerous cells in the body leaving room for the new cells to reach the 
bone marrow and grow into cancer free blood cells. Due to high doses of treatment patients 
receive prior to HSCT, greater than 90% are likely to experience emesis despite the use of anti-
emetics (Faiman, 2016). 
 
Chemo-induced nausea, vomiting, and retching (CINVR) is the most severe and interfering 
symptom experienced by patients (Stricker & Wesmiller, 2015) and affects treatment-related 
quality of life (Wood, Chapman, & Eilers, 2011).  High dose conditioning regimens damage the 
gastrointestinal mucosa and activate brain receptors, causing impulses to increase heart rate, 
respiratory rate, and saliva to cause CINVR (Faiman, 2016). CINVR may be more severe in the 


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delayed phase for patients receiving HSCT, defined as 24 hours after chemotherapy and lasting 
up to 7 or more days (Flank, 2017). Anxiety and depression are also common symptoms (Seo 
et al., 2019), due to prolonged hospitalization (4 weeks or more) separating patients from the 
comfort of their home and social network. Additionally, HSCT may be anxiety provoking as a 
last-option treatment for some patients that have experienced several treatment failures and 
cancer relapse(s). 
 
Alternative therapies may be a promising approach to decrease symptom burden post HSCT.  A 
systematic review evaluating effects of alternative therapies in HSCT patients found that mind 
and body interventions could aid in reducing anxiety, fatigue, and pain (Chakraborty, Savani, 
Litzow, Mohty, & Hashmi, 2015). Systematic and narrative reviews found that use of inhaled 
aromatherapy with essential oils decreased nausea/vomiting (Farahani et al., 2019; 
Keyhanmehr et al., 2018; Toniolo et al., 2021) and anxiety (Boehm et al., 2012; Farahani et al., 
2019; Kayhanmehr et al., 2018) in several studies in the general oncology population. 
Peppermint was a common essential oil used for nausea/vomiting symptoms (Farahani et al., 
2019; Keyhanmehr et al., 2018) and lavender was used most frequently for anxiety symptoms 
(Farahani et al., 2019). Additionally, randomized controlled trails have found statistically 
significant improvements in anxiety symptoms in participants that received inhaled essential oils 
compared to control (Blackburn et al., 2017; Ozkaraman et al., 2018). Only one aromatherapy 
study involving HSCT was identified, which was a randomized controlled trial that did not find 
aromatherapy benefit in hospitalized children newly diagnosed with acute leukemia (Ndao et al., 
2012). Due to the lack of research, there is limited understanding of aromatherapy efficacy in 
the HSCT population. Research is needed to expand translation of aromatherapy as an 
evidence-based practice to populations at high risk for treatment-related complications, such as 
HSCT. Findings from this study will enhance understanding of the efficacy of aromatherapy on 
symptom burden in the HSCT population.  
 
2.0 
Objective(s) 
 
2.1 
Primary Objective 
 
The purpose of this study is to evaluate the efficacy of aromatherapy on symptoms of 
CINVR and anxiety for patients hospitalized for hematopoietic stem cell transplant. The 
primary aim will be to evaluate the effect of inhaled aromatherapy on CINVR and anxiety 
symptoms compared to control for 48 hours.    
 
2.2 
Secondary Objective 
 
• 
Evaluate patient satisfaction with aromatherapy at completion of study. 
• 
Evaluate the antiemetic administration between nausea/vomiting symptom 
intervention and control groups during the 48-hour intervention time span.   
• 
Evaluate the number and incidence of unit falls pre and post intervention.  
 
3.0 
Outcome Measures 
 
3.1 
Primary Outcome Measures 
 
Chemotherapy-Induced Nausea, Vomiting and Retching (CINVR)  
CINVR involves three distinct gastrointestinal symptoms (nausea, vomiting, retching) 
influenced by administration of chemotherapy. Nausea is expressed as an unpleasant 


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feeling in the throat/epigastrium that can result in expulsion of stomach content, known 
as vomiting (Rhodes VA, 2001). Retching is the effort to expel stomach contents without 
success (Rhodes VA, 2001). A review of CINVR instruments identified the Rhodes Index 
of Nausea, Vomiting and Retching (INVR) was the only instrument that separately 
assesses all three symptoms (Wood et al., 2011). The INVR will be used to measure 
CINVR and includes 8 Likert-type items on a 5-point scale, with evidence supporting 
reliability (Spearman correlation 0.87) and validity (Rhodes & McDaniel, 1999).  
Completion of the tool will occur at baseline, 24 hour, and 48 hours of intervention. 
 
The primary endpoint for CINVR is the mean INVR score change from (1) baseline to 24 
hours and (2) baseline to 48 hours. We anticipate a 30% reduction in the INVR mean 
score for participants randomized to the intervention group who indicated 
nausea/vomiting as primary symptom of concern. 
 
Anxiety  
Anxiety is excessive or persistent worry about aspects of life ("Understanding the Facts 
of Anxiety Disorders and Depression is the First Step," n.d.). Anxiety will be measured 
using a shortened version of Spielberger’s State Anxiety Inventory (SAI). The original 
SAI contains 20 items to measure state anxiety and items are scored using a 4-point 
Likert-type scale (almost never-almost always) (Spielberger, Gorsuch, Lushene, Vagg, & 
Jacobs, 1983). The SAI instrument has good internal consistency (.86-.95), test-retest 
reliability (.65-.75) (Spielberger et al., 1983), and evidence supporting construct and 
concurrent validity (Spielberger et al., 1983). The shortened SAI retains 6 items (from 
the original 20) and has evidence supporting good internal reliability consistency 
(Cronbach’s alpha .84) and strong construct validity (Abed, Hall, & Moser, 2011). 
Completion of the tool will occur at baseline, 24 hours, and 48 hours of intervention.     
 
The primary endpoint for anxiety is the mean shortened SAI score change from (1) 
baseline to 24 hours and (2) baseline to 48 hours. We anticipate a 30% reduction in the 
SAI mean score for participants randomized to the intervention group who indicated 
anxiety as their primary symptom of concern.  
 
3.2 
Secondary Outcome Measures 
 
Patient Satisfaction with Aromatherapy   
A brief semi-structured questionnaire will also be administered to evaluate patient 
satisfaction with the intervention at the 48-hour completion time. 
 
Evaluate the antiemetic administration between nausea/vomiting symptom 
intervention and control groups 
Data will also be collected from the electronic medical record related to antiemetic 
medications administered (dose, route, frequency) during the 48-hour intervention. 
 
Evaluate the number and incidence of unit falls pre and post intervention 
Fall rates will also be evaluated using the total number of falls reported to the National 
Database of Nurse Quality Indicators during the baseline and intervention timeframes. 
Demographic data will be collected including age, gender, and race/ethnicity.  
 
4.0 
Eligibility Criteria 
 


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Eligibility criteria will be confirmed through review of the electronic medical record and/or 
patient self-report. Pregnancy tests are standardly completed prior to stem cell transplant and 
result will be available prior to study enrollment (if applicable). 
 
4.1 
Inclusion Criteria 
 
• 
Patients from a bone marrow transplant unit or hematology/oncology unit within 
an adult academic health center in the Midwest. 
• 
Adult stem cell transplant inpatients that have received autologous or allogeneic 
transplant and are actively going through therapy.  
• 
Patients must also be alert and oriented, able to interact with the study team, and 
able to read and write English. 
 
4.2 
Exclusion Criteria 
 
• 
Under 18 years of age 
• 
Currently receiving another form of essential oils (e.g., diffuser, essential oil 
roller, lotion with essential oils) within 24 hours of enrollment 
• 
Intubation  
• 
Medical sedation  
• 
Receipt of chimeric antigen receptor T (CAR-T) cells 
• 
History of atrial fibrillation  
• 
History of seizures/epilepsy  
• 
Adhesive allergy or sensitivity  
• 
Currently pregnant  
• 
Prisoner 
• 
Inability to smell 
 
5.0 
Study Design 
 
This study will be a randomized controlled trial. Prior to randomization, participants will be asked 
which symptom, nausea/vomiting or anxiety, is most burdensome for them. Participants will be 
stratified based on their identified symptom of burden (nausea/vomiting or anxiety) and will then 
be randomized to either the intervention or control group, with a target of 50 participants in the 
nausea/vomiting symptom group (25 intervention and 25 control) and 50 participants in the 
anxiety symptom group (25 intervention and 25 control). Intervention and control groups will 
receive Wyndmere Naturals, Inc. aromatherapy patches and a symptom journal. Participants in 
the intervention group indicating that nausea/vomiting is the primary symptom of concern will 
receive peppermint inhaled aromatherapy patches (or mandarin if peppermint intolerance 
indicted). Participants in the intervention group indicating that anxiety is the primary symptoms 
of concern with receive lavender inhaled aromatherapy patches. The control group will receive 
non-scented aromatherapy patches (i.e., blank hydrogel adhesive patches without essential oil 
infusion), so it will not be feasible to blind participants to group assignment. The control group 
will have the same interactions with the study team as the intervention group and will complete 
patch changes and a symptom journal to serve as an attention control. 
 
 
 


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Prior to  
Enrollment 
 
 
 
Visit 1:   
Day 4, 5, 6, 
7, or 8 
Post-Transplant  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit 2: 
Day 6, 7, 8,  
9, or 10  
Post-Transplant 
(48 hours) 
 
 
 
 
 
 
 
 
 
6.0 
Enrollment/Randomization 
 
Potential participants will receive an information flyer and brief description of the study in clinic 
prior to stem cell transplant. Flyers will also be available in stem cell transplant classes. The 
Screen all new HSCT admissions for potential participants by inclusion and 
exclusion criteria.  
• 
Obtain consent  
• 
Complete demographic questionnaire (Appendix A)  
Follow-up assessments of study endpoints 
• 
Instruct the patient to complete the 48-hour symptom measures in the journal 
• 
Intervention group will complete a brief intervention satisfaction questionnaire  
• 
Instruct patient to remove patch 
Control  
N = 50 
Intervention  
N = 50 
Perform baseline assessments and Education 
• 
Intervention group to determine target symptom and type of aromatherapy patch 
to be given. 
• 
Educate patient on how to use symptom journal  
• 
Complete baseline symptom measures  
• 
Ask patient to complete follow up assessment independently after 24-hours of 
patch use.   
Administer study intervention 
• 
Control and Intervention group receive 48 hours (6 patches) worth of 
aromatherapy patches to be changed every 8 hours.  
 
Randomize 
Final Assessments 
• 
Review and document antiemetic medication administration from the electronic 
medical record during the 48-hour intervention time frame 
• 
Obtain unit fall total numbers and incidence data from the National Database for 
Nurse Quality Indicators (NDNQI) for 6 


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research team will evaluate the electronic medical record daily for patients meeting inclusion 
criteria for enrollment into the study on admission. Eligibility will be confirmed on admission and 
patients meeting inclusion criteria will be approached by the research team for potential study 
enrollment on post-transplant day 4, 5, 6, 7 or 8. Patients will be approached for potential study 
enrollment and if interested, will consent and begin study interventions post-transplant day 4, 
5, 6, 7, or 8 (depending on day research team approaches). This timeframe will allow the team 
to observe for delayed CINVR and allow for flexibility in the study schedule to account for 
patient or study team member unavailability. The study team will provide a summary of the 
study and will review informed consent and HIPAA authorization documents. Patients that agree 
to participate in the study will sign a consent and HIPAA authorization. Consented participants 
will then be randomly assigned using a random number table generated in Microsoft Excel to 
allocate patients to the intervention or control group.   
 
7.0 
Study Procedures 
 
Materials 
 
Participants will receive Wyndmere Naturals, Inc. aromatherapy patches. The hydrogel adhesive 
patches are infused with essential oil for inhaled aromatherapy treatment. Wyndmere Naturals 
aromatherapy patches were chosen for the study because the produce (1) is not absorbed into 
the skin and (2) can be applied and changed by users. The aromatherapy patches provide an 
occlusive barrier that is hypoallergenic, allowing essential oils to be inhaled without coming in 
direct contact with the skin. Additionally, patches are easy to apply and change for users and 
the product has been used in a randomized control trial in which participants completed patch 
changes and documented in a symptom journal (Lillehei et al., 2015), similar to our protocol 
procedures. The patch manufacturer (Bioesse Technologies, LLC, Minnetonka, MN) 
recommends patch changes every 8 hours because the patch is time-released and can last for 
up to 8 hours. 
 
Procedures 
 
After consenting to study participation, patients will complete a brief demographic questionnaire 
(see Appendix A). Additional patient data (cancer type, chemotherapy regimen, transplant type, 
unit of hospitalization) will be collected from the electronic medical record by a study team 
member. Patients will be asked what symptom they find most concerning (nausea/vomiting or 
anxiety) and will then be randomly assigned to the intervention or control group using a random 
number table based on symptom of concern. After random assignment, the patient will be 
educated on how to use a symptom journal (Appendix B) by a study team member and will be 
asked to complete the baseline symptom measures in the journal. Patients will be instructed to 
complete the same symptom measures on the following day independently (24 hour follow up). 
Patients assigned to the intervention group will receive 48 hours (6 patches) worth of essential 
oil infused (lavender, peppermint, or mandarin) patches. Aromatherapy patches will be applied 
to the patient’s skin containing peppermint, mandarin, or lavender essential oils. Patient 
indicating that nausea/vomiting is their symptom of concern will receive peppermint as the 
default oil or mandarin oil if they have a known intolerance to peppermint. Patients indicating 
that anxiety is their symptom of concern will receive lavender oil. Patients assigned to the 
control group will receive 48 hours (6 patches) worth of  non-scented patches (i.e., blank 
hydrogel adhesive patches without essential oil infusion). Patients in both groups will be 
instructed to change the aromatherapy patch (essential oil infused [intervention group] or non-
scented [control group]) every 8 hours, as recommended by manufacturer, and document the 


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patch change in the symptom journal. Patients in both groups will also be instructed to remove 
the aromatherapy patch and contact the study team with and signs/symptoms of sensitivity to 
the patch adhesive or essential oil. The study team will post an “aromatherapy in use” sign 
inside the patient room to notify clinicians that the patient is on study, with instructions to 
remove the aromatherapy patch before a MRI test. 
 
The study team initial visit will be at 0 hours (visit 1) and follow-up visits will be completed at 24 
hours (visit 2) and 48 hours (visit 3). During visit 2 (Monday-Friday only), the study team will 
remind participating patients to complete their symptom journal, will answer any study-related 
questions, and will inquire about any aromatherapy side effects. During visit 3, a study team 
member will instruct the patient to complete the 48-hour symptom measures in the journal and 
will complete a brief intervention satisfaction questionnaire (Appendix C) with the patient 
(intervention group only). Patients will be provided a $25 gift card to show appreciation for their 
time in the study. After symptom data collection is completed, a study team member will review 
and document antiemetic medication administration from the electronic medical record during 
the 48-hour intervention time frame. Antiemetic administration will be captured on an Excel 
spreadsheet on a secure Microsoft Team for intervention and control participants in the 
nausea/vomiting sypmtom group. Included medications are scopolamine, lorazepam, 
promethazine, prochlorperazine, olanzapine, dexamethasone, Marinol, and ondansetron 
indicated for nausea/vomiting. Medication type, dose, order type (scheduled vs. PRN), and 
number of doses will be documented for antiemetics administered during the study timeframe. 
Concomitant medications (e.g., antiemetic medications, steroids, benzodiazepines) will not be 
controlled as part of the study as the intent is not to alter standard practice for symptom 
treatment, but rather to provide an adjuvant to help reduce symptom burden. However, it is 
reasonable to expect that the need for PRN (available as needed) medications prescribed for 
nausea/vomiting or anxiety may be less in the treatment group compared to control during the 
48 hours of inhaled aromatherapy. Because antiemetic and benzodiazepine medications may 
contribute to an increase in fall risk (Seppala et al., 2018; Wildes et al., 2018), we also plan to 
observe fall events during the study timeframe. Unit fall total numbers and incidence data will 
additionally be obtained from data reported to the National Database for Nurse Quality 
Indicators (NDNQI) for 12 months prior to implementation and 12 months during study 
implementation. 
 
8.0 
Study Calendar 
 
 
Screening 
Visit 1 
Visit 2 
*M-F only 
Visit 3 
Secondary 
Data 
Day- 
Admission 
Day 4-8 
(0-hours) 
Day 5-9 
(24-hours) 
Day 6-10 
(48-hours) 
Post Study 
STUDY PROCEDURES 
 
 
 
 
 
Screen new admissions for 
inclusion/exclusion criteria  
x 
 
 
 
 
Consent  
 
x 
 
 
 
Demographic Questionnaire 
 
x 
 
 
 
Symptom Assessment Tools 
 
x 
x 
x 
 
Apply Patch 
 
x 
 
 
 
Satisfaction Questionnaire- 
Intervention Group 
 
 
 
x 
 
Remove Patch 
 
 
 
x 
 
Evaluate Antiemetic Use 
 
 
 
 
x 
Evaluate Falls  
 
 
 
 
x 


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9.0 
Reportable Events 
 
Inhaled essential oils including lavender, peppermint, and mandarin are generally considered 
safe if used as indicated. The essential oils used in this study are infused within an adhesive 
patch, so will not come in direct contact with the skin. However, if the essential oil patch is used 
not as indicated (e.g. oil applied directly to the skin, oil ingested), the risk of adverse event 
occurrence may increase. 
 
Adverse Event:  Defined as any problematic medical occurrence in a study participant who 
has received the intervention including inhaled lavender, peppermint, or mandarin essential oil, 
regardless of possibility of a causal relationship. Adverse events will be documented after the 
participant begins receiving the intervention.  
 
The occurrence and nature of each participant’s medical condition will be documented by study 
personnel prior to enrollment. Study personnel will document any changes in medical condition 
and/or the occurrence and description of any adverse event during the study. Events that occur 
from inhaled essential oil administration up to 72 hours after will be recorded (allows for 24 
hours of monitoring after intervention ends). Events will be reviewed during data safety 
monitoring to determine causality. 
 
Significant Adverse Event:  Defined as a life-threatening condition (i.e. immediate risk of 
dying); severe/permanent disability; a significant hazard, contraindication, side effect, or 
precaution as deemed by the Data Safety Monitoring team to be caused by the intervention. 
Investigators will determine causality based on the participant’s clinical course, medical history, 
and administered medications. 
 
Adverse and Significant Adverse Events will be reported to the IRB within 5 business days from 
discovery if they are determined to be (1) unexpected; (2) related or possibly related to 
participation in the study; (3) finding suggests that the research procedures involve a greater 
harm risk than previously anticipated; (4) occurrence of unanticipated adverse device effects.  
 
10.0 Data Safety Monitoring 
 
The study investigator will meet with study key personnel to review data quality, subject 
recruitment, accrual, retention, and outcome and adverse event data. Study team review will 
occur on a weekly basis to provide monitoring updates and discuss safety/quality concerns. If 
an adverse event occurs in which causality cannot be determined by the research team, the 
study investigator will consult with the patient’s medical team to clarify/confirm event causality. 
Based on findings from the weekly review, considerations for protocol adjustment will be made 
in the event that opportunities are identified to improve participant safety and/or data quality.  
 
This study will be conducted in accordance with the IU Simon Cancer Center Institutional DSMP 
for Low Risk Trials.  
 
Investigators will conduct continuous review of data and subject safety. Quarterly review 
meetings for low risk trials are required and will include the principal investigator, clinical 


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research specialist and/or research nurse (other members per principal investigator’s 
discretion). Quarterly meeting summaries should include review of data, the number of 
subjects, significant toxicities as described in the protocol, and responses observed. Study 
teams should maintain meeting minutes and attendance for submission to the DSMC upon 
request.  
 
Data and Safety Monitoring Committee  
 
The IUSCC Data and Safety Monitoring Committee (DSMC) is responsible for oversight of 
subject safety, regulatory compliance, and data integrity for this trial. The DSMC will review this 
study annually to review overall trial progress, toxicity, compliance, data integrity, and accrual 
per the Institutional DSMP.  
 
Furthermore, the DSMC conducts an administrative review of serious adverse events (SAEs), 
deviations, reportable events, and any other outstanding business. Major issues may require 
further DSMC review or action.  
 
At any time during the conduct of the trial, if it is the opinion of the investigators that the risks 
(or benefits) to the subject warrant early closure of the study, the DSMC Chair and Compliance 
Officer must be notified within 1 business day via email, and the IRB must be notified within 5 
business days. Alternatively, the DSMC may initiate suspension or early closure of the study 
based on its review.  
 
Study Auditing and Monitoring  
 
All trials conducted at the IUSCC are subject to auditing and/or monitoring per the Institutional 
DSMP. Reports will be reviewed by the full DSMC at the time of study review.  
 
Data Management/ Oncore Reporting Requirements  
 
The DSMC reviews data and study progress directly from Oncore; therefore, timely data entry 
and status updates are vital. Study data must be entered within Oncore promptly, no later than 
one week from study visit occurrence. Subject status in Oncore will be updated in real time, as 
this may affect overall trial enrollment status. Global SAEs and deviations will be reviewed on a 
monthly basis by the DSMC Chair directly from Oncore.  
 
Study Accrual Oversight  
 
Accrual data will be entered into the IU Simon Cancer Center OnCore system. The Protocol 
Progress Committee (PPC) reviews study accrual twice per year, while the PPC coordinator 
reviews accrual quarterly.  
 
Oncore Safety Reporting  
 
In addition to protocol- and regulatory-required safety reporting, all serious adverse events 
(SAEs) will be captured in the Oncore system within 1 business day of notification. Initial SAE 
reporting will include as much detail as available, with follow-up to provide complete 


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information. Attributions will be assessed to study drugs, procedures, study disease, and other 
alternate etiology.  
 
Protocol Deviation Reporting  
 
Protocol deviations will be entered into OnCore within 5 days of discovery and reviewed by the 
DSMC Chair on a monthly basis. Findings will be reported to the full DSMC at the time of study 
review. For serious or repetitive protocol deviations, additional action may be required by the 
DSMC. 
 
11.0 Study Withdrawal/Discontinuation 
 
Participants may withdrawal anytime by notifying the principle investigator (Monica Bates) or 
any other member of the study team. Choosing not to participate or withdrawal from the study 
will not influence relationships or patient status at IU Health. 
 
 
12.0 Statistical Considerations 
 
SAS and/or R statistical packages will be used to analyze primary outcomes, secondary 
outcomes, and demographic sample data.  
 
Primary Outcomes  
 
Comparisons between the intervention and control groups for differences in the CINVR and 
anxiety tools will be analyzed using mixed-model ANOVA, with time (baseline, 24 hours, 48 
hours) repeated within subject. Chi-square tests will be used to compare the groups for 
differences in the proportions of patients prescribed medications for nausea/vomiting or 
anxiety. Separate analyses will be performed for the two symptom groups. A two-sided 5% 
significance level will be used for all tests. 
 
Sample size justification: With sample sizes of 50 patients within each symptom group, 25 
intervention/25 control within each symptom group, the study will have 80% power to detect 
an effect size of 0.81 between intervention and control within each symptom group, based on a 
two-sample t-test calculation and a two-sided 5% significance level. The recruitment target will 
be 112 participants (56 per symptom group) to account for a 10% drop out rate. 
 
Secondary Outcomes 
 
Descriptive statistics will be used to analyze frequencies and percentages of the patient 
satisfaction questionnaire responses, documented antiemetic administration, and number of 
unit falls. The number of (1) total antiemetic medication doses and (2) doses for each individual 
medication (i.e., Ativan, promethazine) will be compared between the control and intervention 
groups for the nausea/vomiting sypmtom group. The percentage change for number of falls will 
be calculated by comparing number of falls 12 months prior to intervention implementation to 
12 months during implementation. 
 


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Descriptive statistics will be used to summarize the demographics of the study sample 
(frequencies and percentages for categorical variables, means and standard deviations for 
continuous variables).  
 
13.0 Data Management 
 
Patient data collected from the electronic medical record will be documented in a secure 
electronic REDCap database. Paper signed informed consents and HIPAA authorizations will 
be stored in a file in a locked office. Demographic data, data from the symptom journal, and 
intervention satisfaction responses will be transferred from paper by a study team member into 
REDCap and paper documents will be stored in a secure, locked office. This study involves 
minimal risk for participants. All data will be stored via secure REDCap database, which is 
backed up automatically every day. Only study team members will have access to the data. All 
computers used for data storage and analysis will be password protected. Only aggregated data 
will be disseminated, and raw data will be destroyed after data analysis is complete. 
 
14.0 Privacy/Confidentiality Issues 
 
All data will be stored on a secure REDCap database. All computers used for data storage and 
analysis will be password protected and only trained study personnel will have access to data. A 
unique blinded identifier will be assigned to each participant record prior to analysis. The results 
of the study will be analyzed and reported as aggregate data and no participant or individual 
responses will be identified. 
 
15.0 Follow-up and Record Retention 
 
Study duration including data collection and analysis will take approximately eighteen months.  
Once data collection has been completed and data analyzed, completed assessments will be 
stored on a secure REDCap database. Once it has been determined that original data is no 
longer needed, data files will be secured with password protected computer, and all paperwork 
associated with the study will be discarded via a security container. Data, analysis, and consent 
forms will be secured for the required length of time required by the IRB and then will be 
destroyed appropriately. 
 
16.0 References 
 
Abed, M. A., Hall, L. A., & Moser, D. K. (2011). Spielberger's State Anxiety Inventory: 
Development of a Shortened Version for Critically Ill Patients. Issues in Mental Health 
Nursing, 32(4), 220-227. doi:10.3109/01612840.2010.546493 
Blackburn, L., Achor, S., Allen, B., Bauchmire, N., Dunnington, D., Klisovic, R. B., … Chipps, E. 
(2017). The effect of aromatherapy on insomnia and other common symptoms among 
patients with acute leukemia. Oncology Nursing Forum, 44(4), E185–E193. 
https://doi.org/10.1188/17.ONF.E185-E193 
Boehm, K., Bussing, A., & Ostermann, T. (2012). AROMATHERAPY AS AN ADJUVANT 
TREATMENT IN CANCER CARE – A DESCRIPTIVE SYSTEMATIC REVIEW. 
Retrieved from https://www.ulib.iupui.edu/cgi-
bin/proxy.pl?url=https://search.ebscohost.com/login.aspx?direct=true&db=edsbas&AN=e
dsbas.DD131E03&site=eds-live 


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Chakraborty, R., Savani, B. N., Litzow, M., Mohty, M., & Hashmi, S. (2015). A perspective on 
complementary/alternative medicine use among survivors of hematopoietic stem cell 
transplant: Benefits and uncertainties. Cancer, 121(14), 2303-2313. 
doi:10.1002/cncr.29382 
Faiman, B. (2016). BMTCN certification review manual Pittsburgh, PA: Oncology Nursing 
Society  
Farahani, M. A., Afsargharehbagh, R., Marandi, F., Moradi, M., Hashemi, S.-M., Moghadam, M. 
P., & Balouchi, A. (2019). Effect of aromatherapy on cancer complications: A systematic 
review. doi:10.1016/j.ctim.2019.08.003 
Keyhanmehr, A. S., Kolouri, S., Heydarirad, G., Mofid, B., & Mosavat, S. H. (2018). 
Aromatherapy for the management of cancer complications: A narrative review. 
Complementary Therapies in Clinical Practice. doi:10.1016/j.ctcp.2018.02.009 
Lillehei, A.S., Halcón, L.L., Savik, K., Reis, R., 2015. Effect of inhaled lavender and sleep 
hygiene on self-reported sleep issues: A randomized controlled trial. J. Altern. 
Complement. Med. 21, 430–438. https://doi.org/10.1089/acm.2014.0327 
Ndao, D. H., Ladas, E. J., Cheng, B., Sands, S. A., Snyder, K. T., Garvin, J. H., Jr., & Kelly, K. 
M. (2012). Inhalation aromatherapy in children and adolescents undergoing stem cell 
infusion: results of a placebo-controlled double-blind trial. Psycho-Oncology, 21(3), 247-
254. doi:10.1002/pon.1898 
Özkaraman, A., Dügüm, Ö., Yılmaz, H. Ö., & Yeşilbalkan, Ö. U. (2018). Aromatherapy: The  
effect of lavender on anxiety and sleep quality in patients treated with chemotherapy. 
Clinical Journal of Oncology Nursing, 22(2), 203–210.  
https://doi.org/10.1188/18.CJON.203-210 
Rhodes, V. A., & McDaniel, R. W. (1999). The index of nausea, vomiting, and retching: a new 
format of the index of nausea and vomiting Oncology Nursing Forum, 26(5).  
Rhodes VA, M. R. (2001). Nausea, vomiting, and retching: complex problems in palliative care 
A Cancer Journal for Clinicians 51, 232-248.  
Seo, H. J., Baek, Y. G., Cho, B. S., Kim, T. S., Um, Y. H., & Chae, J. H. (2019). Anxiety and 
Depression of the Patients with Hematological Malignancies during Hospitalization for 
Hematopoietic Stem Cell Transplantation. Psychiatry Investig, 16(10), 751-758. 
doi:10.30773/pi.2019.07.12 
Seppala, L.J., Wermelink, A.M.A.T., de Vries, M., Ploegmakers, K.J., van de Glind, E.M.M., 
Daams, J.G., van der Velde, N., 2018. Fall-Risk-Increasing Drugs: A Systematic Review 
and Meta-Analysis: II. Psychotropics. J. Am. Med. Dir. Assoc. 19, 371.e11-371.e17. 
https://doi.org/10.1016/j.jamda.2017.12.098 
Spielberger, C. D., Gorsuch, R. L., Lushene, R., Vagg, P. R., & Jacobs, G. A. (1983). Manual for 
the State-Trait Anxiety Inventory. Palo Alto, CA. 
Stem Cell Transplantation (n.d.). Leukemia & Lymphoma Society Retrieved from 
https://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation 
Stricker, C. T., & Wesmiller, S. W. (2015). Chemotherapy-Induced Nausea and Vomiting In C. 
G. Brown (Ed.), A Guide to Oncology Symptom Management (2 ed., pp. 171-202). 
Pittsburgh, PA: Oncology Nursing Society  
Toniolo, J., Delaide, V., & Beloni, P. (2021). Effectiveness of Inhaled Aromatherapy on 
Chemotherapy-Induced Nausea and Vomiting: A Systematic Review. The Journal of 
Alternative and Complementary Medicine, 00(00), 1–12. 
https://doi.org/10.1089/acm.2021.0067 


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Understanding the Facts of Anxiety Disorders and Depression is the First Step. (n.d.). Anxiety & 
Depression Association of America. . Retrieved from https://adaa.org/understanding-
anxiety  
Wildes, T.M., Maggiore, R.J., Tew, W.P., Smith, D., Sun, C.-L., Cohen, H., Mohile, S.G., Gajra, 
A., Klepin, H.D., Owusu, C., Gross, C.P., Muss, H., Chapman, A., Lichtman, S.M., 
Katheria, V., Hurria, A., 2018. Factors Associated with Falls in Older Adults with Cancer: A 
Validated Model from the Cancer and Aging Research Group. Support Care Cancer 26, 
3563–3570. https://doi.org/10.1007/s00520-018-4212-3 
Wood, J. M., Chapman, K., & Eilers, J. (2011). Tools for assessing nausea, vomiting, and 
retching. Cancer Nursing, 34(1), E14-24. doi:10.1097/NCC.0b013e3181e2cd79 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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17.0 Appendix 
 
Appendix A:  Demographic Questionnaire  
 
1. What is your age in years? (or prefer not to say) 
2. What gender do you identify with?  
a. Woman 
b. Man 
c. Transwoman 
d. Transman 
e. Genderqueer 
f. not listed 
g. prefer not to say 
3. What race do you most closely identify with? 
a. White/Non-Hispanic 
b. Latino 
c. Black or African American 
d. Native American or American Indian 
e. Asian or Pacific Islander 
f. Other 
g. Prefer not to say 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix B: Sample of Journal  
 
Page 1 
 
 
 
 
 
 
 
 
 
 
 


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Appendix C:  Aromatherapy Experience/Satisfaction Questionnaire  
 
1. Tell me about your experience with aromatherapy in the hospital. 
2. What was your satisfaction with aromatherapy on a scale of 1-10 (10 being extremely 
satisfied)? 
3. How likely are you to use aromatherapy again in the hospital on a scale of 1-10 (10 
being extremely likely)?