A Randomised-controlled Trial on the Effectiveness of Topical Sesame Oil in Preventing Phlebitis at Intravenous Cannula Sites in Adult Patients
Phase: NA
Conditions: Phlebitis, Thrombophlebitis
Sponsor: National Heart Centre Singapore

 
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STUDY PROTOCOL 
 
PROTOCOL TITLE: 
A RANDOMISED-CONTROLLED TRIAL ON THE EFFECTIVENESS OF TOPICAL SESAME 
OIL IN PREVENTING PHLEBITIS AT INTRAVENOUS CANNULA SITES IN ADULT 
PATIENTS 
 
PROTOCOL NUMBER:  
1 
 
PROTOCOL VERSION:  
4 
PROTOCOL DATE:  
09 JANUARY 2023 
 
PRINCIPAL INVESTIGATOR:  
Tan Jia Xing Jasmine, Senior Staff Nurse, National Heart Centre of Singapore  
 
SITE PRINCIPAL INVESTIGATOR:  
Tan Jia Xing Jasmine, Senior Staff Nurse, National Heart Centre of Singapore  
 
 
CO-INVESTIGATORS: 
Lee Mei Bao Jasmine, Senior Nurse Manager, National Heart Centre of Singapore 
Wong Wei Chi Belinda, Nurse Clinician, National Heart Centre of Singapore 
Ng Lin Ying Amanda, Staff Nurse, National Heart Centre of Singapore 
Eugene Wee Beng Seon, Staff Nurse, National Heart Centre of Singapore 
 
STUDY TEAM MEMBERS: 
 Roslinda Binte Mohamed Idris, NC, National Heart Centre of Singapore 
 Liew Siok Moey, NC, National Heart Centre of Singapore 
 Low Huiling, NC, National Heart Centre of Singapore 
 Ong Xiang Yun Charmaine, ANC, National Heart Centre of Singapore 
 Ng Jing Wei, SSN, National Heart Centre of Singapore 
 Sharifah Nur Dhabitah Bte Syed Shiekh, SSN, National Heart Centre of Singapore 
 Gowri N, SSN, National Heart Centre of Singapore 
 Haziqah Bte Idris, SSN, National Heart Centre of Singapore 
 Kang Yunfang, SSN, National Heart Centre of Singapore 
 Lim Yok Yen, SSN, National Heart Centre of Singapore 
 Tan Phaik Ting, SSN, National Heart Centre of Singapore 
 Wee Shao Chun Venassa, National Heart Centre of Singapore 

 
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Table of Contents 
1. 
BACKGROUND AND RATIONALE................................................................................................. 4 
2. 
HYPOTHESIS AND OBJECTIVES ................................................................................................. 6 
3. 
EXPECTED RISK AND BENEFITS ................................................................................................. 6 
4. 
STUDY POPULATION .................................................................................................................. 6 
4.1. 
LIST THE NUMBER AND NATURE OF SUBJECTS TO BE ENROLLED. ................................................................................ 6 
4.2. 
CRITERIA FOR RECRUITMENT AND RECRUITMENT PROCESS ...................................................................................... 7 
4.3. 
INCLUSION CRITERIA .............................................................................................................................................. 7 
4.4. 
EXCLUSION CRITERIA .............................................................................................................................................. 7 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY ................................................................. 7 
6. 
SAFETY MEASUREMENTS............................................................................................................ 9 
6.1. 
DEFINITIONS .......................................................................................................................................................... 9 
6.2. 
COLLECTING, RECORDING AND REPORTING OF SERIOUS ADVERSE EVENTS (SAES) TO CIRB .................................. 10 
6.3. 
SAFETY MONITORING PLAN ................................................................................................................................... 10 
6.4. 
COMPLAINT HANDLING .......................................................................................................................................... 10 
7. 
DATA ANALYSIS........................................................................................................................ 11 
7.1. 
DATA QUALITY ASSURANCE ................................................................................................................................... 11 
7.2. 
DATA ENTRY AND STORAGE .................................................................................................................................. 11 
8. 
SAMPLE SIZE AND STATISTICAL METHODS ............................................................................. 11 
8.1. 
DETERMINATION OF SAMPLE SIZE ......................................................................................................................... 11 
8.2. 
STATISTICAL AND ANALYTICAL PLANS .................................................................................................................... 11 
9. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................................................... 12 
10. QUALITY CONTROL AND QUALITY ASSURANCE ...................................................................... 12 
11. ETHICAL CONSIDERATIONS ..................................................................................................... 12 
11.1. 
INFORMED CONSENT ............................................................................................................................................. 13 
11.2. 
CONFIDENTIALITY OF DATA AND PATIENT RECORDS .............................................................................................. 13 
12. PUBLICATIONS ......................................................................................................................... 13 
13. RETENTION OF STUDY DOCUMENTS ........................................................................................ 13 
14. FUNDING AND INSURANCE ...................................................................................................... 14 
LIST OF ATTACHMENTS .................................................................................................................... 14 
 
 
 
 

 
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PROTOCOL SIGNATURE PAGE 
 
 
 
Protocol Title: A Randomised- controlled trial on the effectiveness of topical sesame oil in preventing 
phlebitis at intravenous cannula sites in adult patients 
 
 
Protocol Number: 1 
 
 
Protocol Version/ Date: 4/ 09 January 2023 
 
 
Sponsor Name: National Heart Centre of Singapore 
 
 
 
Declaration of Investigator 
 
I confirm that I have read the above-mentioned protocol and its attachments. I agree to conduct the 
described study in compliance with all stipulations of the protocol, regulations and ICH E6 Guideline for 
Good Clinical Practice (GCP).  
 
  
 
 
Principal Investigator Name:  Tan Jia Xing Jasmine 
                                                            
 
 
Principal Investigator Signature:   
                                                            
 
 
Date:  09 January 2023 
                                                            
 
 
 
 
 
 

 
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1. 
BACKGROUND AND RATIONALE 
 
The insertion of peripheral intravenous (IV) cannulas for the administration of medications, fluid and 
blood products is commonplace in hospitals today (1). Peripheral IV cannulas are minimally invasive and 
offer physicians and nurses the convenience of administering IV therapy as necessary (2). However, 
despite the many therapeutic benefits that IV cannulas offer, they can lead to complications such as 
infiltration, extravasation, bleeding, bruising, infection and phlebitis (2, 3). Of all the aforementioned 
complications, phlebitis is one of the most common and has been found to affect 5 to 75% of patients 
undergoing IV therapy in hospitals (4, 5).  
Phlebitis refers to the inflammation of the venous tract and its surrounding tissues (5, 6). It can be caused 
by mechanical trauma, chemical irritation or infectious microorganisms (5, 7). Mechanical phlebitis results 
when the inserted IV cannula moves within the vein, causing friction and subsequently inflammation (8). 
Chemical phlebitis is caused by solutions that are hypertonic (osmolality > 500mOsm/litre) or are too 
acidic or alkali in nature (pH < 5 or pH > 9) (9). Infective phlebitis results when bacteria penetrate the 
vein, from the time of insertion or the initiation of IV therapy, and colonise the site, leading to 
inflammation and in serious cases, systemic sepsis (10). 
 
The signs and symptoms associated with phlebitis include varying degrees of one or more of the 
following: erythema, pain, oedema, warmth, palpable venous cords, and purulent drainage (4). Using the 
VIP scale as modified by Jackson (4), the phlebitis grading can range from 0, indicating no signs of 
phlebitis, to 5, with symptoms of redness, pyrexia, a palpable venous cord and purulent drainage (4).  
Although phlebitis is not a fatal diagnosis, it may cause permanent damage to the venous endothelium, 
thereby reducing the possibility of administering IV therapy via the damaged vein in future (11). It has 
also been found that patients diagnosed with phlebitis after their first IV cannula insertion were 5.1 times 
more likely to develop post-infusion phlebitis with subsequent cannulations (12). The development of 
phlebitis often leads to the early withdrawal and reinsertion of the peripheral IV cannula (6). It can cause 
a disruption in IV therapy, added stress and discomfort to patients, lengthened hospital stays (13), and an 
increase in healthcare costs (14). As such, the development of a protocol that aids in preventing the 
exacerbation and reducing the severity of phlebitis in hospitals, is of utmost importance.  
While several topical and systemic therapies have been proposed in literature throughout the years, there 
is a lack of conclusive evidence on the optimal management of phlebitis in clinical practice (15). In all 
three causes of phlebitis (mechanical, chemical, infective), inflammation of the venous tract and its 
surrounding tissues will lead to the development and progression of phlebitis-related symptoms at the IV 
cannula site. As such, the use of anti-inflammatory agents in preventing and treating phlebitis have been 
widely studied and recommended (7, 16-18).  
Oral and topical non-steroidal anti-inflammatory drugs (NSAIDs) have been found to be effective in the 
prevention (16, 17) and treatment of phlebitis (18, 19). Cokmez et al. (17) observed that the incidence of 
phlebitis was halved with the daily use of a topical NSAID gel at the cannula site (17). Similar findings 
were obtained in a study by Babaieasl et al. (16) where the use of topical Diclofenac, produced significantly 
lower incidences of phlebitis as compared to patients who received EMLA or a placebo. In another study, 

 
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both topical and oral Diclofenac were found to be more effective in improving the clinical signs and 
symptoms of phlebitis when compared against patients who received no intervention (18).  
Local inflammation and septicaemia at IV cannula sites have also been found to be correlated with 
positive cultures of the IV cannulas post removal (17, 20). This is largely attributed to poor practices 
during IV cannula insertion and drug administration, which increase the risk of bacteria introduction into 
the vein (10, 16, 21). The use of topical antibiotic and antiseptic agents have thus been advocated for the 
treatment of phlebitis (22). Antibiotics are however not recommended for local wound therapy, because 
of limitations in effectiveness and the potential contribution to the formation of antibiotic-resistant strains 
(23). Antiseptic or plant-based agents like iodine and sesame oil, on the contrary, possess broad spectrum 
antimicrobial effects, are effective on biofilms, possess anti-inflammatory properties and promote wound 
healing, without any risk of contributing to bacterial resistance (10, 23, 24, 25, 26).  
To date, there have been three studies conducted to evaluate the effectiveness of Povidone-iodine in 
preventing phlebitis (27-29). In 1980, Noble et al. (27) tested the effectiveness of a daily Povidone-iodine 
0.5% dry powder application at IV cannula sites, in reducing phlebitis. Two studies by Thompson et al 
(28, 29) likewise studied the effectiveness of Povidone-iodine at preventing phlebitis at IV cannula sites, 
when applied once immediately upon insertion. All three studies (27, 28, 29) found that iodine was not 
effective in preventing the incidence of phlebitis or reducing the incidence of cannula colonisation (27).  
Sesame oil however, has been found to be effective in preventing phlebitis at IV cannula sites in several 
studies (30, 31, 32). Nekuzad et al. (30) conducted a study on patients undergoing chemotherapy, and 
found that phlebitis was eight times more frequent in the control group, where no topical agent was 
applied, than in the intervention group, where topical sesame oil was applied twice a day. Another study 
by Bagheri et al. (31) found that sesame oil was effective at reducing the prevalence and severity of 
phlebitis, for patients on IV Amiodarone. 78% of patients in the control group developed phlebitis with 
the application of a placebo, as compared to 39% of patients in the treatment group with the application 
of sesame oil at the IV cannula site (31). Of these, 6%, 28% and 44% of patients in the control group 
developed grade 2, 3 and 4 phlebitis respectively, while 17% and 22% of the patients in the treatment 
group developed grade 2 and 3 phlebitis respectively. The third study by Pan et al. (32) compared the 
effectiveness of sesame oil, Vitamin E and Sanyrene oil on preventing phlebitis. It was found that only 
37% of patients who had sesame oil applied at the IV cannula site had developed phlebitis, as compared 
to 43% of patients who received Vitamin E, and 76% of patients who received Sanyrene oil. Sesame oil 
was thus found to be twice as effective at preventing phlebitis at IV cannula sites, as compared to Sanyrene 
oil (32). 
 
Though there are no topical agents to date that have been proven to be effective at completely preventing 
or treating phlebitis, the evidence on sesame oil leads us to believe that it is a safe, readily available, low-
cost, and effective agent, that can be used to prevent and reduce the severity of phlebitis at IV cannula 
sites.  
 
 
 
 

 
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2. 
HYPOTHESIS AND OBJECTIVES 
 
Hypothesis:  
The application of topical sesame oil will be effective at preventing phlebitis at peripheral IV cannula sites 
in adult patients within the cardiovascular and cardiothoracic department of a tertiary hospital. 
 
Aim of study:  
• To determine the effectiveness of topical sesame oil in preventing phlebitis at peripheral IV cannula 
sites in adult patients within a cardiovascular and cardiothoracic department of a tertiary hospital.  
Objectives:  
• To measure the incidence and severity of phlebitis at 12 hour intervals, at peripheral IV cannula sites, 
in adult patients within a cardiovascular and cardiothoracic department of a tertiary hospital.  
• To measure the incidence and severity of phlebitis 12 hourly for up to 24 hours post IV cannula removal. 
• To compare the incidence and severity of phlebitis at 12 hour intervals, between patients who received 
topical sesame oil and patients who received topical liquid paraffin oil at the IV cannula site, in adult 
patients within a cardiovascular and cardiothoracic department of a tertiary hospital.  
 
 
3. 
EXPECTED RISK AND BENEFITS 
 
Potential risks: 
• Skin irritation from allergic reactions to sesame oil or liquid paraffin oil  
Potential benefits: 
• Reduced risk in developing phlebitis at the IV cannula site due to the topical application of sesame 
oil. (direct) 
 
• Gained knowledge with regards to phlebitis risk factors, signs and symptoms and consequences. 
(Indirect)  
 
 
 
4. 
STUDY POPULATION 
 
4.1. 
List the number and nature of subjects to be enrolled.  
 
650 adult patients between the age of 21 to 80, and from inpatient wards within The National Heart 
Centre of Singapore will be recruited, regardless of ethnicity or gender. 

 
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4.2. 
Criteria for Recruitment and Recruitment Process 
 
All newly admitted patients with an existing IV cannula will be approached after being admitted into an 
inpatient ward. This will take place within 12 hours of the IV cannula insertion. They will not be 
approached if in distress, drowsy or immediately prior to a surgical procedure. The IV cannula will be 
tested for patency, and assessed for redness, swelling, pain, a palpable venous cord or pyrexia. If any of 
these symptoms are present, or if the IV cannula is not patent, the recruitment will be terminated. 
 
4.3. 
Inclusion Criteria 
 
• Age 21-80 
• Patients must speak and understand either English or Mandarin 
• Patients who possess a peripheral IV cannula 
• IV cannula must have been inserted for less than 12 hours 
• IV cannula must be on an upper extremity 
• IV cannula must be patent 
• IV cannula sites must show no signs of redness, swelling, pain, a palpable venous cord or pyrexia 
• Patient must be admitted to a cardiology ward in the National Heart Centre Singapore  
 
4.4. 
Exclusion Criteria 
 
• Patients who do not speak or understand either English or Mandarin 
• Patients with venous insufficiency 
• Patients with coagulopathies 
• Patients with cognitive or sensory impairments that would inhibit their ability to rate their pain 
via a Numerical Rating Scale (NRS)  
• Patients who are receiving medications that might interfere with timely reporting of adverse 
events (eg. medications that cause severe drowsiness) 
• Patients who report allergies to sesame or liquid paraffin oil 
• IV cannulas that were inserted and used for resuscitation 
• Patients with existing skin conditions that cause their skin to be red or swollen and might affect 
the investigators ability to assess for phlebitis 
• Patients who possess more than one peripheral IV cannula will only be included in the study once. 
All subsequent IV cannula insertions will be excluded.  
 
 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY 
 
A physical copy of the informed consent form will be provided to the inpatient wards included 
in the study. Ward staff will also be briefed verbally on the research details, data collection 
methods and safety information of the study. 
 

 
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Ward nurses will notify investigators, of any patient who has been admitted to the ward 
with an existing IV cannula, or has had a new IV cannula set in the last 12 hours. The 
investigators will review the patient’s medical history to assess for venous insufficiencies, 
coagulation disorders, cognitive or sensory impairments, and medications that might interfere 
with the timely reporting of adverse events. Patients will be approached after being admitted 
into an inpatient ward, within 12 hours of the IV cannula insertion. They will not be approached 
if in distress, drowsy or immediately prior to a surgical procedure. The investigator will access 
the patency of the peripheral IV cannula, and the IV cannula site for signs of redness, swelling, pain, 
a palpable venous cord or pyrexia. If the patient meets the criteria for inclusion, informed consent 
will be taken at the patient’s bedside, in the presence of a witness, with drawn curtains to 
maintain privacy, reduce distractions and prevent undue influence from other individuals within 
the ward. The participant will be given time to consider their participation before giving their 
response to the investigator at the bedside. If they require more time for consideration, the 
investigator will leave the bedside and contact them again within 12 hours of IV cannula 
insertion to confirm recruitment. The investigator will emphasise the patient's right to make their 
own decision with regards to participating in the study. All details of the study and risks and 
benefits will be provided without any pressure on the patient to be recruited. 
 
The patient will then be randomly allocated to the experimental or control group with the use 
of a randomisation software (MS excel). 5 drops/0.25mls of 100% sesame oil or mineral oil will 
be applied to the IV cannula site, from 3cm above the insertion point to 10cm along the vein, 
with a width of 2cm on either side (Appendix A). There will be no massaging or manipulation 
of the infusion site during application. 
 
Demographic and clinical data will be recorded into a table. The patient will be instructed not 
to wash or wipe the topical agent off. The time and date of the start of treatment applied and 
subsequent treatments at 12 hour intervals will be documented. At the start of the study and 
at each 12 hour interval, the investigator will observe for signs of phlebitis using the Visual 
Infusion Phlebitis scoring tool [Appendix 2], before application of the next treatment. The 
study investigators will be the only ones applying the treatment/control and completing the 
data collection form [Appendix 3] every 12 hours. Patient identifiers (name and NRIC) will be 
verified before every application of the treatment/control and the completion of the data 
collection form. 
 
Application of the treatment or control will be made every 12 hours for up to 72 hours, 
where the IV cannula will then be removed according to hospital guidelines. The IV cannula 
site will be observed, every 12 hours for up to 24 hours post IV cannula removal, for 
phlebitis or complications. 
 
Patients will be withdrawn from the study the moment they show signs of adverse reactions 
from the topical treatment or control. 
 
Participants will be involved in the study for a maximum of 96 hours. If the IV cannula is 
removed accidentally or not due to phlebitis before the 72-hour period is up, re-insertion of a 
new cannula and re-application of oils will not be done on a new site. The patient’s IV cannula 
site will continue to be observed for 24 hours at 12-hour intervals after cannula removal. The 
partial data will be kept and analysed. If the patient is discharged before the 96 hour observation 
period is up, the 24 hour post-removal observation will continue to be carried out at 12 hour 
intervals, via phone call or video call. The patients’ phone numbers will be obtained during the 
informed consent process, only for follow up purposes.  

 
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The application of either sesame oil or liquid paraffin oil is not part of the routine procedures or 
standard of care in the ward, and will only be applied for the purpose of this research. Both the 
sesame oil and liquid paraffin oil are marketed products and will be used as per label. 
 
The study is estimated to continue for two years, commencing in February 2022 and ending in 
December 2023. 
 
At no point of the study will any audio or video recording take place.  
 
All hardcopy research data will be stored in in a locked cupboard with lock and key access within 
the National Heart Centre, Singapore. All soft copies will be stored in a password protected 
Laptop belonging to the principal investigator. Only the principal investigator will have access 
to the research data. All other members of the research team will access the data through the 
principal investigator. The physical research data will be kept under lock and key for 7 years 
after the completion of the research study or date of publication of the research using the 
research data, whichever is later. After which, all data will be destroyed. Hardcopies will be 
shredded and soft copies will be deleted. 
 
Subjects may withdraw voluntarily from participation in the study at any time. Subjects may also 
withdraw voluntarily from receiving the study intervention for any reason. Upon withdrawal, IV 
cannula sites will continue to be observed for 24 hours at 12-hour intervals for potential reactions to 
the oils or signs of phlebitis. If there are any adverse reactions to the oils or signs of phlebitis during 
the 24-hour observation period, the patient will be referred to the attending physician and medical 
treatment will be rendered. The patient will continue to receive follow-up and medical treatment until 
symptoms have resolved. 
 
The study may be discontinued at any time, if safety issues arise. If the risks to participants 
unexpectedly outweigh the benefits due to unexpected severe adverse events due to the application 
of the treatment or control oils, the study may then be suspended until the risk-benefit ratio is re-
evaluated. 
 
 
6. 
SAFETY MEASUREMENTS 
6.1. 
Definitions 
 
Serious adverse event (SAE) in relation to human biomedical research, means any untoward 
medical occurrence as a result of any human biomedical research which: 
• results in or contributes to death 
• is life-threatening 
• requires in-patient hospitalisation or prolongation of existing hospitalisation 
• results in or contributes to persistent or significant disability/incapacity or 
• results in or contributes to a congenital anomaly/birth defect 
• results in such other events as may be prescribed  
 

 
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Adverse event (AE) in relation to human biomedical research means any untoward medical 
occurrence as a result of any human biomedical research which is NOT serious.  Adverse event 
can be any unfavourable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease possibly/ probably/ definitely associated with the participant in the human 
biomedical research. 
 
6.2. 
Collecting, Recording and Reporting of Serious Adverse Events (SAEs) to CIRB 
 
Only related SAEs (definitely/ probably/ possibly) will be reported to CIRB. Related means there 
is a reasonable possibility that the event may have been caused by participation in the research.  
Please refer to the CIRB website for more information on Reporting Requirement and Timeline 
for Serious Adverse Events. 
 
The investigator is responsible for informing CIRB after first knowledge that the case qualifies 
for reporting. Follow-up information will be actively sought and submitted as it becomes 
available.  
 
Related AEs will not be reported to CIRB.  However, the investigator is responsible to keep 
record of such AEs cases at the Study Site File. 
 
6.3. 
Safety Monitoring Plan 
 
All participants will have their IV cannula sites monitored for adverse reactions to the application 
of the treatment or control oils, and for signs of phlebitis every 12 hours. Participants will also be 
educated on the signs of allergies or sensitivities to the oils, and the signs of phlebitis. They will 
be advised to contact the investigators immediately upon detection of adverse reactions or 
phlebitis. The moment they experience any adverse reactions to the topical oils, they will be 
withdrawn from the study. A referral will be made to the attending physician in the ward, and 
treatment will be rendered. The participant will continue to receive follow up, observations and 
treatment until the reactions or symptoms resolve. 
 
All hardcopy research data will be stored in in a locked cupboard with lock and key access 
within the National Heart Centre, Singapore. All soft copies will be stored in a password 
protected Laptop belonging to the principal investigator. Only the principal investigator 
will have access to the research data. All other members of the research team will access the 
data through the principal investigator. The physical research data will be kept under lock 
and key for 7 years after the completion of the research study or date of publication of the 
research using the research data, whichever is later. After which, all data will be destroyed. 
Hardcopies will be shredded and soft copies will be deleted. 
 
 
6.4. 
Complaint Handling  
 
The investigators in the study will respond to and try to resolve any study-related concern or 
complaint that is received. If a significant complaint or concern arises, in that a participant’s safety, 
rights or welfare may be severely impacted, it will be reported to the Singhealth Centralised 
Institutional Review Board (IRB). 
 
 

 
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7. 
DATA ANALYSIS 
7.1. 
Data Quality Assurance 
 
Study investigators will be the only ones applying the treatment/control and completing the 
data collection form every 12 hours. Patient identifiers (name and NRIC) will be verified 
before every application of the treatment/control and the completion of the data 
collection form. The principal investigator will perform weekly checks and random audits to 
ensure that all informed consent forms and data collection forms are completed accurately.  
 
7.2. 
Data Entry and Storage 
 
Informed consent forms will be on paper. Data will be both on paper, and entered and stored 
electronically.  The physical research data will be kept under lock and key for 7 years after 
the completion of the research study or date of publication of the research using the research 
data, whichever is later. After which, all data will be destroyed. Hardcopies will be shredded 
and soft copies will be deleted. 
 
 
8. 
SAMPLE SIZE AND STATISTICAL METHODS 
 
8.1. 
Determination of Sample Size  
 
Using a power analysis of 20% and a difference of 35%, a sample size of 44 participants is 
required if subgroup analysis is not required. We then rounded it up to 100 to account for 
an attrition rate of 5%. 
 
Data will be analysed with the Statistical Package for Social Science (SPSS) software 
program (v. 28) using descriptive statistics such as relative and absolute frequencies, mean 
and standard deviation, and inferential statistics such as Chi-square, independent t-test and 
Hazard ratio. 
 
8.2. 
Statistical and Analytical Plans 
a. General Considerations 
 
The distribution and dispersion of the data will be examined through descriptive numerical 
summaries and graphical tools such as scatter plots, via SPSS. The data will then be analysed using 
descriptive statistics such as relative and absolute frequencies, mean and standard deviation, and 
inferential statistics such as Chi-square, independent t-test and Hazard ratio.  
 
As missing data can potentially spoil or invalidate a study, we will spare no effort in minimising incomplete 
or missing data. All data will be carefully inspected to identify missing items and outliers. In the analysis 
of incomplete data, we will consult with a biostatistician regarding the use of incomplete-data analysis 
strategies that will allow us to utilise the available information effectively. 
 
b. Safety Analyses 
 

 
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All adverse events, such as the development of allergic reactions to the oils, leading to the 
participant’s withdrawal from the study will be collected and tabulated. Incidences and severity of 
phlebitis experienced during the course of the study will also be collected and tabulated. All 
adverse reactions and phlebitis incidences will be tabulated for both the treatment and control 
group. The extent and severity of symptoms will also be documented. For phlebitis incidences, 
the severity will be assessed with the Visual Infusion Phlebitis (VIP) scoring tool [Appendix 2]. 
The number of adverse reactions will be summarised for both the treatment and control group. 
Frequency counts and percentages will be calculated and reported. 
 
c. Interim Analyses 
 
We will compare treatment groups on descriptive and clinical characteristics at baseline to ensure 
that randomisation has succeeded. SPSS will be used for group comparisons, descriptive 
calculations and conditional regression modelling. We will examine the distributions of all 
important variables at baseline and at the end of the data collection period, to assess for covariate 
imbalance. Formal statistical methods to test for selection bias will be used. 
 
 
9. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
 
The investigators and the National Heart Centre of Singapore will permit study-related 
monitoring, audits and/or IRB review and regulatory inspection(s), providing direct access to 
source data/document. All physical data required will be accessed through the primary 
investigator. 
 
 
 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE 
 
The primary investigator will review all physical data and conduct random audits to assess for 
adherence with the protocol. She will also assess all data weekly for accuracy and completeness.  
 
 
 
11. 
ETHICAL CONSIDERATIONS 
 
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and that are consistent with the Good Clinical Practice and the applicable 
regulatory requirements. 
 
This final Study Protocol, including the final version of the Participant Information and Consent 
Form, must be approved in writing by the Centralised Institutional Review Board (CIRB), prior 
to enrolment of any patient into the study. 
 
The principal investigator is responsible for informing the CIRB of any amendments to the 
protocol or other study-related documents, as per local requirement. 
 

 
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11.1. Informed Consent 
 
Informed consent will be taken at the patient’s bedside by an investigator of the study, in the 
presence of a witness, with drawn curtains to maintain privacy, reduce distractions and 
prevent undue influence from other individuals within the ward. The participant will be given 
time to consider their participation before giving their response to the investigator at the 
bedside. If they require more time for consideration, the investigator will leave the bedside 
and contact them again within 12 hours of IV cannula insertion to confirm recruitment. 
The investigator will emphasise the patient's right to make their own decision with regards to 
participating in the study. All details of the study and risks and benefits will be provided 
without any pressure on the patient to be recruited. 
 
11.2. Confidentiality of Data and Patient Records 
 
All hardcopy data collected will be stored in a locked cabinet within the National Heart Centre of 
Singapore. Only the principal investigator will have access to the locked cabinet. Investigators 
may access the data via the principal investigator. Electronic data will be stored on a password 
protected laptop belonging to the principal investigator, and access to the data will be restricted 
to the investigators of this research study.  
 
 
12. 
PUBLICATIONS 
 
All investigators involved in this study will be given authorship for scientific publications. Other 
persons who may have contributed in some capacity, such as those who may have provided advice 
with regards to the research, or assisted with data analysis, will be acknowledged with their 
approval. The contributions of each author will be reviewed thoroughly to ensure that they meet 
the criteria of authorship for the respective journals. Should a journal require assurances that all 
non-author contributions agree to being named in the acknowledgements, or that no non-author 
contributors have been omitted from the acknowledgements, signed agreements will be provided 
on request. 
 
 
13. 
RETENTION OF STUDY DOCUMENTS 
 
Records for all participants, including CRFs, all source documentation (containing evidence to 
study eligibility, history and physical findings, etc.) as well as IRB records and other regulatory 
documentation will be retained by the PI in a secure storage facility. The records will be accessible 
for inspection and copying by authorized authorities. The physical research data will be kept 
under lock and key for 7 years after the completion of the research study or date of 
publication of the research using the research data, whichever is later. After which, all data 
will be destroyed. Hardcopies will be shredded and soft copies will be deleted. 
 
 

 
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14. 
FUNDING and INSURANCE 
 
Grant 
 
i. Name of Grant Agency:               National Heart Centre of Singapore Pte Ltd (NHCS) 
ii. Grant Name:                        Lim Suh Fen Cardiovascular Research and Education Fund 
iii. Amount:                                $20090 
iv. Grant Reference Number           07/FY2021/EX/91-A145(a) and 07/FY2021/EX(SLP)/91A145(b) 
 
 
 
List of Attachments 
 
Appendix 1 
References 
 
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2010;74(5):857-8. 
 
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3. Pasalioglu KB, Kaya H. Catheter indwell time and phlebitis development during 
peripheral intravenous catheter administration. Pak J Med Sci. 2014;30(4):725-30.  
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5. Mattox EA. Complications of peripheral venous access devices: Prevention, 
detection, and recovery strategies. Critical Care Nurse. 2017;37(2):e1-e14.  
6. Goulart CB, Custodio CS, Vasques CI, Ferreira EB, Diniz Dos Reis PE. 
Effectiveness of topical interventions to prevent or treat intravenous therapy-related 
phlebitis: A systematic review. J Clin Nurs. 2020;29(13-14):2138-49.  
7. Agarwal S, Verma NC, Singam A. Efficacy of topical heparin in prevention of 
superficial  
thrombophlebitis before peripheral venous cannulation. J Evolution Med Dent Sci. 
2020;9(23):1734-8.  

 
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8. Stokowski G, Steele D, Wilson D. The use of ultrasound to improve practice and 
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10. Higginson R, Parry A. Phlebitis treatment, care and prevention. Nurs Times. 
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12. Hadaway L. Short peripheral intravenous catheters and infections. J Infus Nurs. 
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21. Uslusoy E, Mete S. Predisposing factors to phlebitis in patients with peripheral 
intravenous catheters: a descriptive study. J Am Acad Nurse Pract. 2008;20(4):172-80. 
 

 
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22. Fah F, Zimmerli W, Jordi M, Schoenenberger RA. Septic deep venous thrombosis 
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XL, Liou CJ, Li ZY, et al. Inflamm Res.2015;  64:577–588 
 
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28. Thompson DR, Jones GR, Sutton TW. A trial of povidone-iodine ointment for 
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1983;4:285-9. 
 
29. Thompson DR, Jowett NI, Folwell AM, Sutton TW. A trial of povidone-iodine 
antiseptic solution for the prevention of cannula-related thrombophlebitis. J Intraven 
Nurs. 1989;12(2):99-102. 
 
30. Nekuzad, N, Ashke Torab, T, Mojab, F, Alavi-Majd, H, Azadeh, P, & Ehtejab, G. 
Effect of external use of sesame oil in the prevention of chemotherapy-induced 
phlebitis. Iranian Journal of Pharmaceutical Research. 2012;11(4), 1065-1071. 
 
31. Bagheri-Nesami, M, Shorofi, SA, Hashemi-Karoie, SZ, & Khalilian, A. The effects 
of sesame oil on the prevention of Amiodarone-induced phlebitis. Journal of Nursing 
and Midwifery Research. 2015;20, 365-370. 
 
32. Pan, J, Zhao, D, Sui, J, Jia, L, Han, R, & Lin, Y. Clinical effect of three topical 
drugs in preventing phlebitis caused by intravenous infusion of the nutrient solution. 
Nursing of Integrated Traditional Chinese and Western Medicine. 2020;6(2), 108-110. 
 
33. Gallant P, Schultz AA. Evaluation of a visual infusion phlebitis scale for 
determining appropriate discontinuation of peripheral intravenous catheters. J Infus 
Nurs. 2006;29(6):338-45. 

 
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34. INS. Infusion Nursing Standards of Practice. Journal of Infusion Nursing. 
2011;34(1s).  
 
 

 
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Appendix 2  
Visual Infusion Phlebitis Scoring Tool
 
 
 
RESITE CANNULA 
This tool was modified for use in this study. 

 
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Appendix 3  
Data Collection Form