Evaluating Gastro-oesophageal Reflux After Palliative Stenting for Malignant Distal Oesophageal Obstruction Using Anti-Reflux Stents: a Randomised Controlled Trial
Phase: NA
Conditions: Esophageal Cancer, Reflux, Gastroesophageal
Sponsor: University of Cape Town

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Study Protocol for: 
 
Evaluating Gastro-oesophageal Reflux after Palliative Stenting for 
Malignant Distal Oesophageal Obstruction using Anti-Reflux Stents: 
a Randomised Controlled Trial 
 
University of Cape Town Human Research Ethics Committee Approval Number: 
HREC REF: 706/2021 
NCT Number not yet availbale 
 
Date of Document Version: 09/03/2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Evaluating Gastro-oesophageal Reflux after Palliative Stenting for 
Malignant Distal Oesophageal Obstruction using Anti-Reflux Stents: 
a Randomised Controlled Trial 
 
 
Dr Matthias F Scriba 
Upper Gastrointestinal Surgery, Surgical Gastroenterology 
Division of General Surgery 
Groote Schuur Hospital, University of Cape Town 
matthias.scriba@gmail.com 
 
Dr Galya E Chinnery 
Upper Gastrointestinal Surgery, Surgical Gastroenterology 
Division of General Surgery 
Groote Schuur Hospital, University of Cape Town 
galya.chinnery@uct.ac.za 
 
Dr Chanel G Robinson 
Mitchell’s Plain Hospital 
chanelgr@gmail.com 
 
Dr Barbara Robertson 
Department of Radiation Oncology 
Groote Schuur Hospital, University of Cape Town 
barbara.robertson@uct.ac.za 
 
Dr Rene Krause 
Department of Palliative Care 
Groote Schuur Hospital, University of Cape Town 
rene.krause@uct.ac.za 
 
Dr Stuart More 
Department of Nuclear Medicine 
Groote Schuur Hospital, University of Cape Town 
stuart.more@uct.ac.za 
 
Anna-Lena Du Toit 
Department of Dietetics 
Groote Schuur Hospital, University of Cape Town 
Anna-lena.dutoit@westerncape.gov.za 
 
Prof Eduard G Jonas 
Head of Surgical Gastroenterology 
Division of General Surgery 
Groote Schuur Hospital, University of Cape Town 
eduard.jonas@uct.ac.za 
 
 

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BACKGROUND 
Oesophageal cancer is an aggressive condition, resulting in the vast majority of patients having 
evidence of locally invasive, irresectable disease or distant metastases at the time of presentation1. 
Overall survival remains poor. Management in the South African setting is plagued by late 
presentation of these patients2, with less than 5% being eligible for curative treatment 3,4 and median 
survival from the time of diagnosis being only 15 weeks4, while those who present with complete 
obstruction having a median survival of only 75 days (10.7 weeks)5. Treatment of these patients in the 
South African setting remains predominantly palliative. The most common and debilitating symptom 
of advanced oesophageal malignancy is progressive dysphagia1, which can be addressed by the 
endoscopic placement of self-expanding metal stents. The major drawback of stenting tumours in the 
lower oesophagus or oesophagogastric junction (OGJ), is the associated gastro-oesophageal reflux 
(GOR) resulting from the stent crossing the lower oesophageal sphincter and essentially negating the 
native anti-reflux mechanism.  Significant reflux is the most common complaint worsening quality of 
life after stent placement in these patients and can be as high as 100% in some series6. Prescribing 
routine proton pump inhibitors (PPIs) or placing stents with built-in anti-reflux mechanisms are 
methods aimed at reducing this symptomatic reflux 1.  
 
Diagnosis of GOR in general remains a challenge and numerous diagnostic tests are available. As no 
specific validation has been done for GOR assessment after placement of oesophageal stents, data on 
diagnostic techniques of GOR are taken from the primary health care setting or from studies looking 
at patients who are being considered for, or who have had, anti-reflux surgery. International 
guidelines, such as the American College of Gastroenterology7, propose that typical symptoms of GOR 
confirm a presumptive diagnosis and should prompt empiric medical management (usually with PPIs). 
Further special investigations to confirm GOR include upper gastrointestinal endoscopy and 
ambulatory pH monitoring. Barium radiography and oesophageal manometry are not typically 
recommended as part of the diagnostic work-up7.   
 
However, all of these tests have drawbacks. Accuracy of diagnosis using only patient-reported 
symptomatology is non-invasive and with the addition of validated questionnaires8, reasonably 
accurate, but it remains subjective and may not differentiate pathological reflux from functional 
dyspepsia. Endoscopy may reveal visual evidence of GOR, such as reflux oesophagitis or Barrett’s 
oesophagus, which unequivocally prove the presence of GOR7. However, non-erosive reflux disease, 
which is the most common form of GOR, may show no visible abnormalities on endoscopy7. Twenty-
four-hour pH studies give an objective measure of acid content in the oesophagus and allow for 
matching of patient reported symptoms to reflux events. Accuracy is further increased when 
impedance is added to the pH-metry as this will diagnose non-acid reflux which is missed when pH-
metry is used alone7. Despite reported high accuracy rates using pH-impedance studies in patients 
with erosive reflux disease, the accuracy rates drop significantly in patients with endoscopy-negative 
GOR7. The necessity of a trans-nasal catheter for a period of 24 hours, also makes this test more 
invasive than other modalities. 
 
Although not included in these guidelines, oesophageal scintigraphy is a diagnostic modality available 
to objectively confirm and quantify gastric contents refluxing up the oesophagus. It has the advantage 
of assessing oesophageal transit, GOR and gastric emptying9. Scintigraphy has also been shown to be 
an accurate modality to confirm the presence of laryngopharyngeal reflux or gastric content aspiration 
into the lungs10. Although not commonly described in the literature on the diagnosis of GOR in adults, 
its use is much more common in the paediatric setting. International paediatric guidelines11 describe 
the use of oesophageal scintigraphy in diagnosing GOR, although there is insufficient evidence to 

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support the routine use of scintigraphy in making the diagnosis. Scintigraphy remains the standard 
technique for assessing gastric emptying, which if delayed, may be an important underlying cause for 
GOR11. Despite the guidelines, the use of scintigraphy to diagnose GOR is considered very useful in 
paediatrics 12 and is commonly used in some institutions. The Red Cross War Memorial Children’s 
Hospital routinely use oesophageal scintigraphy, the so-called “milk scan”, to work up paediatric 
patients with suspected severe reflux who might require anti-reflux surgery13. The role of scintigraphy 
in the diagnosis of GOR in the adult setting remains undefined.   
 
Theoretically, oesophageal stents containing an anti-reflux valve should provide a physical barrier to 
prevent gastric content (which may be acidic or non-acidic) refluxing into the oesophagus, but 
whether this results in decreased rates of GOR in reality is somewhat controversial. To date, a number 
of trials have compared a range of anti-reflux oesophageal stents to conventional oesophageal stents 
and although there have been some conflicting results, a systematic review and meta-analysis in 20191 
concludes that GOR is not significantly reduced by the use of anti-reflux stents. However, there are a 
number of factors that must be mentioned before this conclusion can be applied to dictate clinical 
practice. Firstly, the included trials all have reasonably small participant numbers, with 65 patients 
being the highest number of patients enrolled in any of these trials 14. In fact, the authors conclude 
that the meta-analysis is underpowered. Furthermore, the type of anti-reflux stent used varies with 
almost every trial and may well influence efficacy of reducing GOR. Anti-reflux medical therapy such 
as the use of proton pump inhibitors (PPIs) also varied greatly amongst the studies. Some prescribed 
PPIs only to the conventional stent group 15, others did not use PPIs in either group 16, while the rest 
did not mention whether PPIs were routinely given or not. This could possibly influence symptomatic 
reflux and act as a significant confounding factor.  
 
The measurement of GOR in the trials assessed in this meta-analysis shows significant heterogeneity, 
with some studies using patient questionnaires (some of these assess quality of life in general and do 
not specifically focus on reflux symptoms), others use contrast oesophagography 15,17 or functional 24-
hour pH monitoring 16,18,19. These additional factors make the results of this underpowered meta-
analysis difficult to interpret. 
 
Since then, a further randomised controlled trial (RCT) was conducted by Dua et al 6. This included a 
total of 60 patients, comparing a novel tricuspid-shaped valve anti-reflux stent (30 patients) to 
conventional stenting (30 patients). Importantly, this trial was a non-inferiority trial to assess safety 
and efficacy at improving dysphagia for the new stent. Assessment of GOR was a secondary outcome 
and although reflux rates favoured the new anti-reflux stent, this did not reach statistical significance. 
The current level I and II evidence on reducing GOR with anti-reflux stents is thus not definitive and 
leaves the topic unresolved. 
 
What is less controversial, are the data on safety and efficacy at dysphagia improvement using anti-
reflux stents. The pooled data of the meta-analysis show that there are no significant differences in 
stent-related complications between the anti-reflux stents and conventional stents, specifically stent 
migration, bleeding and stent occlusion 1. Improvement in dysphagia was similar between the two 
stents, actually slightly favouring the anti-reflux stent group, but not reaching statistical significance. 
Another systematic review and meta-analysis focusing specifically on oesophageal stents placed for 
malignant obstruction, showed that treatment-related deaths were actually reduced when anti-reflux 
stents were used 20. Thus, using anti-reflux oesophageal stents does not raise any additional safety 
concerns when compared to conventional stents.  
 

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While research in high income countries is focused on the management of early oesophageal 
malignancies, this is not appropriate in the South African setting where the vast majority of patients 
are irresectable at initial presentation. Local research is significantly limited21 and there is a paucity of 
data from South Africa, and Africa as a whole, as regards the palliative management of malignant 
oesophageal dysphagia. Specific evidence on the use of anti-reflux stents is absent. Further research 
is thus invaluable in assessing if the palliative care of these patients can be improved by using anti-
reflux stents. 
 
This prospective randomised controlled trial aims to compare the incidence of symptomatic volume 
GOR after the use of anti-reflux oesophageal covered metal stents versus conventional oesophageal 
covered metal stents for lower oesophageal malignant strictures in a South African tertiary referral 
centre with a high rate of palliative stenting for advanced oesophageal carcinoma.    
 
AIM AND OBJECTIVES 
Aim 
This prospective randomised controlled trial will aim to compare symptomatic volume GOR, when 
using anti-reflux oesophageal stents versus conventional oesophageal stents, in the palliative 
management of patients with lower oesophageal or OGJ carcinomas.  
 
Primary Objective/Hypothesis to be Tested 
The primary objectives of this trial will be to compare rates of self-reported, symptomatic volume GOR 
and objectively measured rates of volume GOR using scintigraphy, between the two study groups. This 
will be a superiority trial, with the hypothesis being that palliative oesophageal anti-reflux self-
expanding fully covered metal stents significantly reduce volume GOR compared to conventional 
oesophageal self-expanding fully covered metal stents.    
 
Secondary Objectives 
Secondary objectives will be to compare outcomes, including rates of dysphagia, cough, pain, stent-
related complications, subsequent complications and patient survival at the end of the study period. 
A further objective will be to compare the self-reported GOR questionnaire (GerdQ) outcomes to the 
objectively measured oesophageal scintigraphy measurements. 
 
METHODS 
Trial Design 
This study will be a prospective randomised controlled trial comparing anti-reflux oesophageal stents 
to conventional oesophageal stents. Randomisation to an anti-reflux stent versus a conventional stent 
will be done prior to stent placement and the patient will remain blinded to the type of stent placed. 
Although the authors will not be blinded to the stent type, as the stents are easily distinguished from 
each other at the time of endoscopy, the Clinical Coordinator who will be doing the follow-up will be 
blinded to this. This study will be performed following the CONSORT 2010 checklist of information for 
randomised trials 22. 
 
Once the study is approved by the University of Cape Town’s Human Research Ethics Committee, 
approval for the study will also be obtained from Groote Schuur Hospital. The trial will then be 
registered with the South African National Clinical Trials Register (SANCTR) and at clinicaltrials.gov. 
Both stents being compared in this trial are already approved by the South African Health Products 

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Regulatory Authority (SAHPRA), and as they form part of standard of care, application to SAHPRA will 
not be necessary. 
 
Participants 
Eligibility criteria for trial participants: 
 
Inclusion Criteria (all criteria must be met): 
• 
Adult patients - 18 years of age or older 
• 
Informed consent obtained from the patient after oral and written explanation of the trial 
• 
Histologically confirmed malignancy of the distal oesophagus or OGJ 
• 
Obstructive or irresectable malignancy due to metastases, local tumour infiltration or poor 
performance status  
• 
Once deployed, the distal end of the stent must have crossed the OGJ junction and be lying 
within the proximal stomach 
 
Exclusion Criteria: 
• 
Patient declining or unable to give informed consent, including inability to speak or 
understand either English, Afrikaans or isiXhosa.  
• 
Patient unable to comply with the follow-up protocol of the trial (e.g. does not have a 
contactable telephone number) 
• 
Oesophageal cancers selected for curative treatment or irresectable oesophageal cancers 
selected for palliative chemoradiation, but not requiring oesophageal stenting 
• 
Benign oesophageal pathology or extrinsic compression of the oesophagus from another 
cause 
• 
Patients with oesophageal cancers where the stent does not cross the OGJ 
• 
Pregnant patients 
• 
Patient performance status precluding any intervention or sedation 
 
Setting and Location of Trial 
This trial will take place at the Upper Gastrointestinal Surgery Unit at Groote Schuur Hospital (GSH). 
All stent insertions for the trial will be performed by either of the two full-time consultants working in 
the Upper Gastrointestinal Surgery Unit at GSH. Palliative oesophageal stenting is performed in the 
endoscopy suite in E23 under conscious sedation. After appropriate post-procedural observation in 
the unit, the patient will be admitted to the hospital for overnight observation and if deemed well 
enough, will be discharged home the following day after the scintigraphy.  
 
Interventions 
Patients considered eligible for the trial will be enrolled after obtaining informed consent. 
Oesophageal stenting will be performed according to standard practices at the GSH endoscopy suite 
using video endoscopy (standard gastroscope) and fluoroscopy. Patients will be appropriately sedated 
for the procedure, provided with supplemental oxygen and a diagnostic upper gastrointestinal 
endoscopy will then be performed to confirm the site and length of the histologically confirmed 
oesophageal cancer. Randomisation will then occur only if stenting is required which will result in OGJ 
overlap. Regardless of which type of stent the patient receives, all enrolled participants will be 
prescribed a twice daily dose of a proton pump inhibitor post the procedure, which is continued 
indefinitely as per the current standard of care at GSH.  
 

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Randomisation will be done using opaque, sealed envelopes with computer-generated random 
numbers in blocks of 20 (10:10). Patients will be randomised to either receive a conventional 
oesophageal stent or an anti-reflux oesophageal stent. Other than the anti-reflux mechanism, all other 
parameters of the two stents will be the same – both stents will be fully covered Nitinol self-expanding 
metal stents designed for deployment in the oesophagus (conventional stent: Taewoong Niti-S 
Esophageal Covered Stent, distributor: First Medical Company [Global Medical Device Nomenclature 
Code 61751] and anti-reflux stent: Taewoong Niti-S Esophageal Covered AR Stent, distributor: First 
Medical Company [Global Medical Device Nomenclature Code 48136]). Both stent types come in a 
standard length of 120mm. Both of these stents are available and currently form part of the standard 
of care at GSH, although the stent selection is determined by stent availability and endoscopist 
preference – the conventional stent is generally favoured. Both are approved by SAHPRA as part of 
First Medical’s list of approved devices they can import into and distributed in South Africa. 
 
The technique of stent deployment will also be the same for both anti-reflux and conventional stents. 
Stent position and deployment success will be confirmed after stent placement, using water-soluble 
contrast injected through the stent under fluoroscopy – this will confirm the distal stent position 
crossing the OGJ. The patient will remain unaware of which type of stent they are receiving. The 
progress of the trial will be documented according to the CONSORT 2010 flow diagram22.  
 
Follow-up 
Technical success of the stent insertion will be confirmed using fluoroscopy immediately after 
insertion. Any insertion-related complications will be documented. All patients will be appropriately 
observed in the gastrointestinal unit after the procedure and then admitted to the ward for overnight 
observation. They will undergo scintigraphy the following day (day 1 post the procedure) and then if 
deemed well enough will be either discharged home or referred back to their referring hospital. The 
follow-up period will subsequently continue for a total of 8 weeks.  
 
Patients with palliative oesophageal cancer are in most instances frail and have a significantly limited 
life expectancy. It is thus imperative upon discharge, that further research-related follow-up should 
not inconvenience the patient nor have a negative effect on their quality of life. Furthermore, many 
of the patients treated at GSH have limited financial means to afford repeated follow-ups at the 
hospital. For these reasons, subsequent follow-up after discharge, will be done telephonically. Patients 
will be phoned at 1, 2, 4 and 8 weeks post stent insertion and will be asked about any symptoms 
related to the stent insertion, and have an assessment of symptomatic GOR using the GerdQ 
questionnaire 8, dysphagia, cough and pain levels at each telephonic follow-up. Telephonic follow-up 
of these patients will be done by the Clinical Coordinator, who is blinded to which type of stent the 
patient has received.  
 
All patients will also be referred to the GSH Palliative Care Team. With any symptom reported by a 
patient or family member that is deemed to possibly require further intervention or treatment, the 
patient will be requested to return for an evaluation or appropriately managed according to the 
Palliative Care Distress Algorithm (Appendix 1). All complications will be managed as per standard 
treatment routinely employed for such a complication at GSH. Any such complications will be 
documented.  
 
 
 
 
 

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OUTCOME MEASURES 
Primary Outcome Measure 
The primary outcome will be patient-reported rates of symptomatic volume GOR and objectively 
measured volume GOR in both study groups. Patient-reported symptomatic volume GOR will be 
assessed using the validated GerdQ questionnaire (Appendix 2) 8. This questionnaire has been chosen 
has it is simple, easy to understand and includes only 6 questions, which are all reflux-related. This 
questionnaire will be administered to the patient prior to the procedure, to establish a baseline. It will 
then subsequently be telephonically administered at the scheduled telephonic follow-ups at weeks 1, 
2, 4 and 8. The GerdQ questionnaire enables the patient to provide a score at each follow-up 
interaction which can then be documented and the mean scores between the two groups can then be 
compared. 
 
GOR will also be objectively measured on day 1 post stent insertion using scintigraphy. The proposed 
protocol for scintigraphy is described in Appendix 3. This modality has been chosen as its accuracy 
compares favourably to pH monitoring9, but is much less invasive. It requires the patient to swallow a 
meal of soft, runny porridge and then undergo imaging. pH monitoring is invasive, requiring the 
insertion of an uncomfortable nasal probe which stays in-situ for 24 hours, increasing discomfort for 
the patient but also increasing the hospital stay by a further 24 hours. It is thus deemed inappropriate 
in this setting. 
 
Secondary Outcome Measures 
The secondary outcomes that will be assessed will include immediate technical success rate and any 
complications related to the stent insertion, subsequent stent-related complications, patient-reported 
dysphagia score prior to stent insertion, on day 1 post-insertion and then at each of the scheduled 
telephonic follow-ups and lastly, patient survival at 2 months post stent insertion. Dysphagia 
assessment will be done using the modified dysphagia scale first published by Mellow and Pinkas and 
validated for assessing dysphagia after metal stent insertion for oesophageal cancer (Appendix 4)23. 
Furthermore, an assessment of the patient’s pain level and whether they are coughing will also be 
documented, using validated pain24 and cough scores25 and pain (Appendix 5 & 6). 
 
Data Collection 
The following data parameters will be collected: 
• 
Age 
• 
Gender 
• 
Performance status25 and BMI of the patient at time of stent placement  
• 
Histological type of malignancy (e.g. adenocarcinoma, squamous cell carcinoma or other) 
• 
Reason for inoperability: metastases, locally advanced or poor performance status 
• 
Position of oesophageal malignant stricture (endoscopic measurement in centimetres from 
the incisors) 
• 
Patient-reported degree of dysphagia prior to stenting 
• 
Patient-reported GerdQ score pre-stenting 
• 
Stent characteristics: anti-reflux vs conventional, length, diameter and brand name of stent  
• 
Immediate technical success rate 
• 
Immediate stent insertion complications: 
o Bleeding 
o Perforation 
o Other 

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• 
Subsequent stent-related complications during the follow-up period: 
o Bleeding 
o Perforation 
o Migration 
o Stent occlusion and cause thereof 
o Other  
• 
Quantitative assessment of volume reflux as per scintigraphy (on day 1) 
• 
GerdQ score at follow-up at week 1, 2, 4 and 8 
• 
Dysphagia score on day 1 post stent-insertion and at follow-up weeks 1, 2, 4 and 8 
• 
Patient survival outcome at 8 weeks 
• 
Cough and pain score pre-insertion, on day 1 and at 1, 2, 4 and 8 weeks 
 
Data Safety and Monitoring 
A password-protected computer-based registry will be created using REDCap (Research Electronic 
Data Capture). No paper-based data collection sheets will be used to record the data and analysis will 
take place directly from the registry after data exportation into an appropriate statistical software 
programme such as SPSS or Stata. 
 
To protect patient confidentiality: 
• 
Access to the registry will be password protected and will only be accessed by investigators 
on this study. 
• 
Data extracted from the registry to SPSS / Stata will be anonymised and patient details will 
only be identifiable from their designated trial number. 
 
Research Procedures and Data Collection Methods 
All data will be prospectively entered into the electronic registry at the time of stent insertion and at 
the defined post-insertion follow-up periods. Patients will be contacted telephonically at the defined 
post-insertion follow-up periods by the Clinical Coordinator. Other than the scintigraphy, this study 
will require no biological specimens or further special investigations specifically for the purposes of 
the research project.   
 
ETHICAL CONSIDERATIONS 
There will be no additional risk, cost or investigations to the patients if they agree to be included in 
the trial. Patients will only be included in the study after being informed about the study and 
completing the consent form. Patient confidentiality will be maintained. The study will be conducted 
in accordance with: 
 
• 
Guidelines for Good Clinical Practice (GCP) in the conduct of Clinical Trials in Human 
Participants in South Africa. Latest Edition, 2020 (released June 2021).  
• 
The Department of Health: Ethics in Health Research: Principles Structures and Processes 
2004 
• 
The Helsinki Declaration.  
 
All efforts will be made to publish the results in an international or local academic peer-reviewed 
journal and submitted for presentation at an appropriate national or international congress. Although 
the patients who are included in the study may not benefit directly from their participation, the results 
may help us manage future patients more effectively. 
 
 

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Description of risks and benefits 
This study will incur no additional risks relating to the trial or research process to the participant. 
Oesophageal stenting is the palliative management of choice in malignant dysphagia. Anti-reflux 
stents as an intervention have been shown not to increase risks or safety concerns compared to 
conventional stents and have similar rates of dysphagia improvement compared to conventional 
stents. Procedure and stent-related risks will thus not be increased due to participation in this trial. 
Both stents form part of current standard of care. Insertion and post-insertion management of these 
patients will be the same as for any patient requiring oesophageal stenting for malignant dysphagia.   
 
The addition of scintigraphy in assessing GOR on day 1 post-insertion, will require the patient to 
consume a soft porridge with a runny consistency containing a small volume of a radio-active 
substance (Appendix 2). Measurements are done using a gamma camera. Although this exposes the 
patient to ionising radiation, the doses are extremely small27 and equate to similar background 
radiation exposure of living in a large city. Any theoretical deleterious effects of such radiation are 
considered negligible in this patient cohort with such a limited life expectancy. The investigation is 
thus not considered to result in additional risks to the patient.  
Informed Consent 
• 
Informed written consent for enrolling in the study will be taken by one of the investigators 
on the day the patient is recruited 
• 
Consent will be taken in a closed consultation room with only the patient, the patient’s family, 
nurse and investigator present 
• 
Where decision-making capacity is questionable, the patient will be excluded from the study 
• 
The patient will be given a consent form explaining their condition and the proposed study 
• 
The consent form complies with the requirements stipulated in the University of Cape Town 
Human Research Ethics Committee (HREC) standard operating procedures 
• 
The consent form is available in English, Afrikaans and isiXhosa 
• 
Information contained in the consent form will be discussed with the patient and family 
members by the investigator 
• 
The patient will be offered the option to take time to think about the information provided 
and discuss it with family members 
• 
If the patient is unable to understand English then an investigator fluent in Afrikaans or Xhosa 
will consent the patient for the study. If an investigator fluent in the necessary language is not 
available then a translator will be used. 
• 
Participation in the trial will be completely voluntary and it will be emphasized that if the 
patient does not wish to participate in the trial, the clinical management of their disease will 
not be affected in anyway and they also have the option to withdraw from the trial at any 
given point.  
 
Privacy and confidentiality 
Patient privacy and confidentiality will be upheld throughout the study period. All patient data will be 
stored on a password-protected registry, which will only be accessible to the investigators and data 
being analysed will be appropriately anonymised.  
 
Reimbursement to Participants 
Participants will not be reimbursed for their participation 
 
Emergency care and insurance for research-related injuries 
This trial is not studying a new or unapproved device and both interventions already form part of the 
standard of care for these patients at GSH, thus specific research-related risks are not considered 

11 
 
significant in this study, and specific research-related emergency care or insurance will not be needed. 
Any stent-related complications will be managed as per standard treatment protocols used by the GSH 
Upper Gastrointestinal Surgery Unit for any patient with an oesophageal stent complication. However, 
the University of Cape Town (UCT) has agreed to act as the Regulatory Sponsor for this trial and as the 
current directive from the UCT Risk Management Office stipulates that all clinical trials need no-fault 
insurance, UCT has agreed to provide such insurance cover for this trial (signed sponsorship 
agreement is submitted separately).  
 
Care after Research 
This trial will not involve a pharmaceutical product or device that requires repeated administration. 
Both stents are inserted as a once-off procedure and unless there is an unforeseen complication (such 
as stent migration or patient intolerance of the stent necessitating removal), these stents usually stay 
in-situ indefinitely. With the unfortunately short life expectancy for this group of patients, most 
participants will require a single stent insertion and will then die with the stent still in-situ. This means 
that once the trial period is over, they will still continue to have the benefit of the stent regardless of 
when the trial ends. If the anti-reflux stents are proven to significantly reduce GOR, those participants 
in the conventional stent group will however not be offered an anti-reflux stent if the stent they have 
received is still functional and without problems. This is because the procedure of exchanging one 
stent for another carries significant risks and in this vulnerable group of patients such a stent exchange 
procedure would not be justified.  
 
Statistical Analysis 
Data will be captured using the REDCap electronic data capturing software licensed to the University 
of Cape Town. All data exploration and analysis will be done using an appropriate statistical software 
programme such as SPSS (version 27.0, IBM, USA). Statistical significance will be set as p <0.05. 
Recorded data will be expressed as mean (SD), or median (interquartile range) when non-normally 
distributed (continuous data). Where continuous data are non-normally distributed, variables will be 
logarithmically transformed prior to inclusion in multivariable statistical analysis.  Dichotomous 
variables will be expressed as proportions or percentages. Baseline demographic and clinical 
characteristics between the anti-reflux stent and the conventional stent group will be compared using 
appropriate statistical tests based on the nature of the data as well as distribution thereof. GOR scores 
between the two groups will be assessed using inferential statistics with the hypothesis that the anti-
reflux stent group will have reduced reflux compared to the conventional stent group. In addition, 
survival analysis will be performed with visual representation using Kaplan Meier curves.  
 
Sample Size 
Using a power calculation for comparison of two continuous data means in a superiority assessment 
(with GerdQ score means as the primary outcome assessed), assuming a 2-point reduction in GerdQ 
mean score between the two groups - mean GerdQ score of 9 in the conventional stent control group 
and a GerdQ score of 7 in the anti-reflux stent group - with a standard deviation of 3, with an alpha 
level of 5% and power set at 80%, a sample size of 72, with 36 in each arm, is required.  
Correlating this to the previous randomised controlled trials, it is noted that these numbers are similar, 
but slightly higher than previous trials. With concerns that a number of these previous trials were 
underpowered, a slightly bigger sample size is deemed appropriate.   
 
 
 
 

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Time Frame 
The study will begin as soon as HREC approval has been granted and the relevant registrations with 
SANCTR and clinicaltrials.gov have been completed. It is expected to run for 36 months. Interim 
analyses of the collected data will be performed at 12 and 24 months. 
  
Budget 
All research-related costs will be covered by the General Surgery and Surgical Gastroenterology 
Research Funds.  
1. Stents:  
Both types of oesophageal stents (conventional and anti-reflux) are currently available at 
Groote Schuur Hospital and as they form part of the standard treatment of these patients, 
will not need to be purchased specifically for this research study.  
2. Scintigraphy: 
R4000 per investigation x 72 patients = R288 000 
3. Clinical coordinator: 
The clinical coordinator for this trial is already employed by the University of Cape Town and 
is very active in multiple research projects within the Surgical Gastroenterology Unit. She will 
thus not need to be renumerated specifically for her assistance in this trial. 
4. Other Costs: 
This trial will not require specific electronic or other research-related equipment or major 
stationary costs. All other minor costs will be borne by the study investigators. 
 
TOTAL COSTS:  
 
R288 000 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Ferndale L, Sartorius B, Aldous C, Thomson SR. Oesophageal cancer in Area 2 of Kwazulu-
Natal: Predictors of late presentation. South African Journal of Surgery 2019;57(2):4–9.  
3.  
Nel D, Omar M, Chinnery G, Jonas E. Disparity in oesophageal cancer management in South 
Africa: A comparison between two tertiary centres with special focus on the palliation of 
dysphagia. South African Journal of Surgery 2019;57(2):10–5.  
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16 
 
APPENDICES 
List of Appendices 
Appendix 1 : Palliative Care Distress Management Algorithm 
Appendix 2: GerdQ score 
Appendix 3: Gastro-oesophageal Scintigraphy Protocol 
Appendix 4: Dysphagia Score 
Appendix 5: Pain Score – Visual Analog (Face) Score 
Appendix 6: Simplified Cough Score 
Appendix 7: Proposed Data Sheet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

17 
 
Appendix 1 : Palliative Care Distress Management Algorithm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
During patient follow-up, whilst 
administering the questionnaire: 
Trial participant displays or expresses 
distress (e.g. extreme emotional 
upset) - questioning is to be stopped 
and the distress protocol implemented 
Trial participant complains of 
uncontrolled symptoms 
Apologize for this line of questioning 
causing distress 
Acknowledge how the line of 
questioning might be distressing 
Give the trial participant the opportunity 
to withdraw from the study 
Reaffirm that withdrawing will not 
jeopardize further management or care 
If participant is more comfortable and 
wishes to continue, proceed 
Offer further counselling by referring to 
social worker 
Check if the patient has a home support 
system (refer ASAP to social worker if not) 
Determine the Home Care 
Service the patient has been 
Contact Home Care 
Service and inform 
them that the patient 
requires urgent 
follow up 
If symptoms are not 
appropriate for Home 
Care Service 
management, advise 
participant or family to 
bring trial participant to 
hospital for assessment 
and management 
Thank the trial participant for their time 

18 
 
Appendix 2: GerdQ score8 
 
 
Appendix 3: Gastro-oesophageal Scintigraphy Protocol 
The following standardised protocol is provided by the Groote Schuur Hospital Nuclear Medicine 
Department for gastric emptying, including GOR assessment: 
 
An Oats meal is given to the patient as part of the study: 
• 
Prepare the Oats meal (soft, runny consistency) before taking the patient to the camera 
room 
• 
Also prepare a small radioactive marker, using a small piece of cotton-wool, to put on 
the Xiphisternum. 
• 
Once the radioactive meal has been prepared, take the patient to the camera room, and 
explain the procedure on how the patient must eat the radioactive meal, especially in 
line with Radiation Protection. 
• 
Ensure that the patient details are entered on the acquisition station, that a workflow is 
ready for the first acquisition, and that the patient is ready for scanning. 
• 
Remove the patient’s clothing from the waist up and place the radioactive marker on the 
Xiphisternum of the patient. Give patient a gown to put on. 
• 
Diabetic patients on Insulin (oral-insulin combo pts incl.): check how much Insulin the 
patient needs to take, the patient needs to take half the dose before eating the meal, 
irrespective if the patient took half a dose of Insulin earlier to lower the glucose. 
• 
Give the patient an apron and a pair of gloves to put on, before handing the radioactive 
meal to the patient.  
• 
The patient needs to finish the meal within 10 min. 
• 
Immediately after the patient finished the radioactive meal, wipe the patient’s mouth 
with paper towel or rinse the mouth, get the patient on the bed and immediately start 
imaging. 
• 
Immediately after the completion of the meal, the patient is positioned in front of the 
camera. The study can be acquired on standing, sitting or supine.    
• 
The same position should be used throughout the study with the camera heads at the 
same distance from the patient. Document all the  
 
Radiopharmaceutical: 
• 
Radioisotope: Technetium-99m (99mTc) 
• 
Pharmaceutical: Tin-Colloid (SnColl) 
• 
Physical T1/2: 6.02 hours 
• 
Principle photo-peaks: 140 keV 
• 
Dose: 20-30 MBq 
 

19 
 
Imaging Protocol: 
• 
Collimator: Low Energy High Resolution (LEHR) 
• 
Starting time post injection: Immediately after the patient has finished the radioactive Oats 
meal. 
• 
Note: a new acquisition series needs to be opened for each acquisition! 
 
• 
Static Acquisition: 
• 
Series: Name the acquisition series according to the time of imaging post last 
+swallow! The first image will be named the exact time after last swallow (e.g. 
STATIC 3min), and the rest of the images will be named according to the imaging 
protocol! (STATIC 0min [i.e. immediately after last swallow], 1hr, 2hr, 3hr, and 4hr) 
• 
Zoom: 1.0 
• 
Camera Preset: Tc99m-NMG 
• 
Detectors: Both Detectors 
• 
Time per view: 60 sec 
• 
View Labels: Label each view according to patient-to-detector orientation, as well as 
the time post last swallow (e.g. Detector 1: ANT 5min, Detector 2: POST 5min). 
• 
Orientation: Head Out 
 
• 
After the STATIC 4hr image, show the Nuclear Medicine Physician to see if any further 
imaging is required. 
 
Sources of Error: 
• 
Vomiting after meal ingestion 
• 
 Poor labelling 
• 
 A nonstandard meal 
• 
A marked variation in the environment, such as noise, lighting, or temperature during 
imaging.  Emotional fluctuations, such as fear of the medical environment, anxieties about 
results, anger after a long wait for the study to begin 
 
Suggested Standard Meal For Gastro-oesophageal Scintigraphy 
• 
Jungle Oatso Easy 50g satchet 
• 
Protifar 14g powder 
• 
Sugar or Replace 10g * 
• 
Boiling water 180 ml 
 
• 
Add boiling water to the dry ingredients 
• 
Stir briskly 
• 
Add and mix 20-30 MBq of Tc99m-Tin colloid 
 
• 
*NOTE 
• 
Replace is tasteless but provides the same amount of carbohydrate as sugar does. In order 
to adjust for individual patient sweet taste preference, the total (10g) sugar or Replace 
should always remain constant, but the proportion of each can be changed. For example: 
• 
5 g sugar + 5 g Replace 
 
 
OR 
• 
10 g sugar + 0 g Replace 
 
 
OR 
• 
0 g sugar + 10 g Replace 
 

20 
 
Appendix 4: Dysphagia Score23 
• 
0 = normal/no dysphagia 
• 
1 = ability to eat some solid food 
• 
2 = ability to eat semisolids only 
• 
3 = ability to swallow liquids only 
• 
4 = complete dysphagia (inability to swallow saliva) 
 
Appendix 5: Pain Score – Visual Analog (Face) Score24 
 
 
 
Appendix 6: Simplified Cough Score25 
 
Score 
Daytime Cough Symptoms 
Nigh-time Cough Symptoms 
0 
No cough 
No cough 
1 
Transient cough occasionally during the 
daytime 
Transient cough before sleep or occasional 
cough during the night 
2 
Frequent cough mildly affecting daily life 
Cough mildly affects night sleep 
3 
Frequent cough severely affecting daily life 
Cough severely affects night sleep 
 
Appendix 7 – Proposed Data Sheet 
1. Participant Trial Number 
2. Patient/Tumour Baseline Characteristics: 
• 
Age 
• 
Gender 
• 
Performance Status (ECOG) 
• 
Co-morbidities 
• 
Substance use 
• 
Body Mass Index 
• 
Histological type of malignancy (SCC, Adenocarcinoma, Other) 
• 
Reason for inoperability (metastases, locally advanced, poor performance status, or other) 
• 
Position of malignancy (endoscopic measurement in centimetres from the incisors) 
• 
Length of tumour 
3. Pre-stenting Scores: 
• 
Dysphagia (pre-stenting) 
• 
GerdQ (pre-stenting) 
• 
Pain (pre-stenting) 
• 
Coughing (pre-stenting) 
4. Stent Insertion: 
• 
Stent characteristics: anti-reflux vs conventional, length, diameter and brand name of stent  

21 
 
• 
Immediate technical success rate 
• 
Immediate stent insertion complications: 
• Bleeding 
• Perforation 
• Incorrect stent placement 
• Other 
5. Day 1 Post-Stenting: 
• 
Scintigraphy Results 
• Oesophageal Clearance 
• Oesophageal Reflux 
• Secondary Clearance 
• Gastric Emptying 
• 
Dysphagia score (day 1) 
• 
Pain score (day 1) 
• 
Coughing score (day 1) 
6. Week 1 Post-stenting: 
• 
GerdQ Score (week 1) 
• 
Dysphagia Score (week 1) 
• 
Pain Score (week 1) 
• 
Coughing Score (week 1) 
7. Week 2 Post-stenting: 
• 
GerdQ Score (week 2) 
• 
Dysphagia Score (week 2) 
• 
Pain Score (week 2) 
• 
Coughing Score (week 2) 
8. Week 4 Post-stenting: 
• 
GerdQ Score (week 4) 
• 
Dysphagia Score (week 4) 
• 
Pain Score (week 4) 
• 
Coughing Score (week 4) 
9. Week 8 Post-stenting: 
• 
GerdQ Score (week 8) 
• 
Dysphagia Score (week 8) 
• 
Pain Score (week 8) 
• 
Coughing Score (week 8) 
10. Outcomes: 
• 
Stent-related complications during the follow-up period: 
• Bleeding 
• Perforation 
• Migration 
• Stent Occlusion and Cause Thereof 
• Perforation 
• Other 
• 
Survival outcome at 8 weeks (alive or dead)