Esophageal CancerNCT05303298
Evaluating Acid Reflux After Oesophageal Stenting Using Anti-reflux Stents
A study testing Anti-reflux oesophageal stent and Conventional oesophageal stent in people with Esophageal Cancer and Reflux, Gastroesophageal, run by University of Cape Town at 1 site in South Africa.
Trial summary
Incurable oesophageal cancer remains a global problem and in South Africa the vast majority of patients with oesophageal cancer have advanced disease at first presentation and are not curable. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer, Reflux, Gastroesophageal
- What is being tested?
- Anti-reflux oesophageal stent and Conventional oesophageal stent
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteSouth Africa
- Study dates
- 1 Oct 2022to 1 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Patient declining or unable to give informed consent, including inability to speak or understand either English, Afrikaans or isiXhosa (the three most commonly spoken local languages).
- 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
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
University of Cape Town
Cape Town, Western Cape, 7925
Matthias F Scriba, FCS (SA), +27 82 295 2611, matthias.scriba@gmail.com
About this study
Official title: Evaluating Gastro-oesophageal Reflux After Palliative Stenting for Malignant Distal Oesophageal Obstruction Using Anti-Reflux Stents: a Randomised Controlled Trial
Incurable oesophageal cancer remains a global problem and in South Africa the vast majority of patients with oesophageal cancer have advanced disease at first presentation and are not curable. Likely the most distressing symptom of advanced cancer in the oesophagus is dysphagia, which is the inability to swallow solids and later also liquids. This is successfully addressed in most cases by the placement of a stent in the oesophagus which opens the area of obstruction. When placed in the lower oesophagus, one of the major drawbacks of these stents is that they disrupt the anti-reflux mechanism of the oesophago-gastric junction, which can result in severe acid reflux, severely impacting the quality of life of the patient. To address this problem, a range of approved anti-reflux stents have been developed and tested in numerous trials. To date, the evidence is conflicting and there is insufficient current evidence to support the routine use of these stents. However, the trials are not all similar in how the acid reflux was measured or what type of stent was used. Furthermore, the use of anti-reflux medication, such as proton pump inhibitors, which may help reduce reflux, are not standardised across the trials and make further conclusions about these stents difficult to interpret.
No data from Sub-Saharan Africa on the use of anti-reflux stents in these patients is available. South Africa faces a large burden of incurable oesophageal cancer and improving the quality of life of these patients is of paramount importance. This randomised controlled trial aims to investigate whether anti-reflux stents do indeed reduce acid reflux in patients with incurable oesophageal cancer compared to conventional oesophageal stents that do not have such an anti-reflux mechanism. Reflux will be measured using patient questionnaires about reflux, and other quality of life parameters, and will also be objectively measured using oesophageal scintigraphy, which has not been used in previous similar trials.
Read the detailed description
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 presentation. Overall survival remains poor. Management in the South African setting is plagued by late presentation of these patients, with less than 5% being eligible for curative treatment and median survival from the time of diagnosis being only 15 weeks, while those who present with complete obstruction having a median survival of only 75 days (10.7 weeks). Treatment of these patients in the South African setting remains predominantly palliative. The most common and debilitating symptom of advanced oesophageal malignancy is progressive dysphagia, 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 series. Prescribing routine proton pump inhibitors (PPIs) or placing stents with built-in anti-reflux mechanisms are methods aimed at reducing this symptomatic reflux.
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 2019 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. 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, others did not use PPIs in either group, 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 or functional 24-hour pH monitoring. 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. 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.
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 limited 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. Reflux will be assessed subjectively by the administration of patient questionnaires aimed at identifying severity of acid reflux, but also the degree of dysphagia, pain and coughing before and after stent placement. Reflux will also be assessed objectively by using oesophageal scintigraphy performed shortly after stent insertion. Scintigraphy has not previously been used to measure GOR in these patients and is chosen for its accuracy and non-invasive nature (compared to, for example, pH monitoring which requires the placement of an uncomfortable nasal probe for 24 hours and is considered inappropriate in this cohort where the main focus lies on quality of life).
- Conditions
- Esophageal Cancer, Reflux, Gastroesophageal
- Being tested
- Anti-reflux oesophageal stent, Conventional oesophageal stent
- Keywords
- Esophageal Cancer, Palliative Stenting, Gastroesophageal Reflux, Anti-reflux Stents
- Medical subject headings
- Esophageal Neoplasms, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-reflux oesophageal stentDevice
Fully covered self-expanding metal stent with anti-reflux mechanism
Conventional oesophageal stentDevice
Fully covered self-expanding metal stent without an anti-reflux mechanism
| Study group | Role | What they receive |
|---|---|---|
| Anti-reflux Oesophageal Stent Group (AOSG) | Experimental | All patients randomised to this arm will receive an anti-reflux fully covered self-expanding metal oesophageal stent Receives: Device: Anti-reflux oesophageal stent |
| Conventional Oesophageal Stent Group (COSG) | Active comparator | All patients randomised to this arm will receive a conventional fully covered self-expanding metal oesophageal stent that does not contain an anti-reflux mechanism Receives: Device: Conventional oesophageal stent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective gastro-oesophageal reflux (GOR) - change in GOR over specified time periods
Self-reported symptomatic reflux using a validated reflux patient questionnaire - the GerdQ questionnaire. GerdQ: score ranges from 0 - 18 points with higher scores equating to higher GOR rates.
Measured: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Objective gastro-oesophageal reflux (GOR)
Objective measure of GOR will be done using oesophageal scintigraphy
Measured: Will be performed as a once-off investigation on day 1 post stenting
Secondary outcomes (5)
Dysphagia - change in dysphagia over specified time periods
Dysphagia will be assessed pre- and post intervention using a validated 5 part dysphagia score described by Knyrim et al - scores are reported as 0 - 5, with higher scores indicating more severe dysphagia.
Measured: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Pain - Change in pain over specified time periods
Pain will be assessed using a validated visual analog pain score using pictures of faces to signify pain. Pain will be rated from 0 - 5, with higher scores indicating more severe pain
Measured: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Cough - change in pain over specified time periods
Cough will be assessed using a validated cough score, the Simplified Cough Score assessing both daytime and night-time cough severity. Score will range from 0 - 6, with higher score indicating worse cough symptoms.
Measured: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Stent-related complications
All complications related to the stent insertion and later complications related to the stent will be documented
Measured: Documentation will occur at the time of stent insertion, day 1 post insertion and then at scheduled follow-ups at weeks 1, 2, 4 and 8 post-insertion or aat any time during the study period if a stent-related complication is reported
Survival
Participant survival will be documented at the end of the study period
Measured: Documented at 8 weeks post stent insertion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start1 Oct 2022
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised to receive either an anti-reflux oesophageal stent or a conventional oesophageal stent.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthias Scriba, University of Cape Town
- Investigators
- Matthias F Scriba, FCS (SA), Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05303298
- Sponsor's protocol ID
- HREC REF NO: 706/2021
- Status last verified
- Nov 2022
- First submitted
- 28 Feb 2022
- Last updated
- 7 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual Participant Data (IPD) that underlie the results reported in the published article for this study, after deidentification, will be made available to any investigator or investigators who request the data for analyses to achieve specific aims of a proposed research study. The study and proposed use of the data must be approved by an independent review committee identified for this purpose. The Study Protocol and Informed Consent Form will also be made available on request. Data will be available immediately after publication of the study and for 5 years after this. Proposals should be directed to matthias.scriba@gmail.com. to gain access, data requestors will need to sign a data access agreement.
Publications
Pandit S, Samant H, Morris J, Alexander SJ. Efficacy and safety of standard and anti-reflux self-expanding metal stent: A systematic review and meta-analysis of randomized controlled trials. World J Gastrointest Endosc. 2019 Apr 16;11(4):271-280. doi: 10.4253/wjge.v11.i4.271.
PubMed 31040888Ferndale L, Sartorius B, Aldous C, Thomson SR. Oesophageal cancer in Area 2 of Kwazulu-Natal: predictors of late presentation. S Afr J Surg. 2019 Jun;57(2):4-9.
PubMed 31342677Nel 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. S Afr J Surg. 2019 Jun;57(2):10-15.
PubMed 31342678Ferndale L, Aldous C, Hift R, Thomson S. Gender Differences in Oesophageal Squamous Cell Carcinoma in a South African Tertiary Hospital. Int J Environ Res Public Health. 2020 Sep 28;17(19):7086. doi: 10.3390/ijerph17197086.
PubMed 32998198Dandara C, Robertson B, Dzobo K, Moodley L, Parker MI. Patient and tumour characteristics as prognostic markers for oesophageal cancer: a retrospective analysis of a cohort of patients at Groote Schuur Hospital. Eur J Cardiothorac Surg. 2016 Feb;49(2):629-34. doi: 10.1093/ejcts/ezv135. Epub 2015 Apr 12.
PubMed 25870217Dua KS, DeWitt JM, Kessler WR, Diehl DL, Draganov PV, Wagh MS, Kahaleh M, Wong Kee Song LM, Khara HS, Khan AH, Aburajab MM, Ballard D, Forsmark CE, Edmundowicz SA, Brauer BC, Tyberg A, Buttar NS, Adler DG. A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video). Gastrointest Endosc. 2019 Jul;90(1):64-74.e3. doi: 10.1016/j.gie.2019.01.013. Epub 2019 Jan 23.
PubMed 30684601Jones R, Junghard O, Dent J, Vakil N, Halling K, Wernersson B, Lind T. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1030-8. doi: 10.1111/j.1365-2036.2009.04142.x. Epub 2009 Sep 8.
PubMed 19737151Blomberg J, Wenger U, Lagergren J, Arnelo U, Agustsson T, Johnsson E, Toth E, Lagergren P. Antireflux stent versus conventional stent in the palliation of distal esophageal cancer. A randomized, multicenter clinical trial. Scand J Gastroenterol. 2010;45(2):208-16. doi: 10.3109/00365520903443860.
PubMed 19968614Coron E, David G, Lecleire S, Jacques J, Le Sidaner A, Barrioz T, Coumaros D, Volteau C, Vedrenne B, Bichard P, Boustiere C, Touchefeu Y, Bregeon J, Prat F, Le Rhun M; Societe Francaise d'Endoscopie Digestive (SFED). Antireflux versus conventional self-expanding metallic Stents (SEMS) for distal esophageal cancer: results of a multicenter randomized trial. Endosc Int Open. 2016 Jun;4(6):E730-6. doi: 10.1055/s-0042-106960.
PubMed 27556085Shim CS, Jung IS, Cheon YK, Ryu CB, Hong SJ, Kim JO, Cho JY, Lee JS, Lee MS, Kim BS. Management of malignant stricture of the esophagogastric junction with a newly designed self-expanding metal stent with an antireflux mechanism. Endoscopy. 2005 Apr;37(4):335-9. doi: 10.1055/s-2005-861113.
PubMed 15824943Sabharwal T, Gulati MS, Fotiadis N, Dourado R, Botha A, Mason R, Adam A. Randomised comparison of the FerX Ella antireflux stent and the ultraflex stent: proton pump inhibitor combination for prevention of post-stent reflux in patients with esophageal carcinoma involving the esophago-gastric junction. J Gastroenterol Hepatol. 2008 May;23(5):723-8. doi: 10.1111/j.1440-1746.2008.05396.x.
PubMed 18410607Power C, Byrne PJ, Lim K, Ravi N, Moore J, Fitzgerald T, Keeling PW, Reynolds JV. Superiority of anti-reflux stent compared with conventional stents in the palliative management of patients with cancer of the lower esophagus and esophago-gastric junction: results of a randomized clinical trial. Dis Esophagus. 2007;20(6):466-70. doi: 10.1111/j.1442-2050.2007.00696.x.
PubMed 17958720Homs MY, Wahab PJ, Kuipers EJ, Steyerberg EW, Grool TA, Haringsma J, Siersema PD. Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial. Gastrointest Endosc. 2004 Nov;60(5):695-702. doi: 10.1016/s0016-5107(04)02047-4.
PubMed 15557944Blum D, Selman LE, Agupio G, Mashao T, Mmoledi K, Moll T, Dinat N, Gwyther L, Sebuyira LM, Ikin B, Downing J, Kaasa S, Higginson IJ, Harding R. Self-report measurement of pain & symptoms in palliative care patients: a comparison of verbal, visual and hand scoring methods in Sub-Saharan Africa. Health Qual Life Outcomes. 2014 Aug 2;12:118. doi: 10.1186/s12955-014-0118-z.
PubMed 25085579Lai K. Chinese National Guidelines on Diagnosis and Management of Cough: consensus and controversy. J Thorac Dis. 2014 Oct;6(Suppl 7):S683-8. doi: 10.3978/j.issn.2072-1439.2014.10.06. No abstract available.
PubMed 25383201
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Gastro-oesophageal Reflux After Palliative Stenting for Malignant Distal Oesophageal Obstruction Using Anti-Reflux Stents: a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT05303298
- Acronym / sponsor ID
- HREC REF NO: 706/2021
- Conditions
- Esophageal Cancer, Reflux, Gastroesophageal
- Keywords
- Esophageal Cancer, Palliative Stenting, Gastroesophageal Reflux, Anti-reflux Stents
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 31 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Incurable oesophageal cancer remains a global problem and in South Africa the vast majority of patients with oesophageal cancer have advanced disease at first presentation and are not curable. Likely the most distressing symptom of advanced cancer in the oesophagus is dysphagia, which is the inability to swallow solids and later also liquids. This is successfully addressed in most cases by the placement of a stent in the oesophagus which opens the area of obstruction. When placed in the lower oesophagus, one of the major drawbacks of these stents is that they disrupt the anti-reflux mechanism of the oesophago-gastric junction, which can result in severe acid reflux, severely impacting the quality of life of the patient. To address this problem, a range of approved anti-reflux stents have been developed and tested in numerous trials. To date, the evidence is conflicting and there is insufficient current evidence to support the routine use of these stents. However, the trials are not all similar in how the acid reflux was measured or what type of stent was used. Furthermore, the use of anti-reflux medication, such as proton pump inhibitors, which may help reduce reflux, are not standardised across the trials and make further conclusions about these stents difficult to interpret.
No data from Sub-Saharan Africa on the use of anti-reflux stents in these patients is available. South Africa faces a large burden of incurable oesophageal cancer and improving the quality of life of these patients is of paramount importance. This randomised controlled trial aims to investigate whether anti-reflux stents do indeed reduce acid reflux in patients with incurable oesophageal cancer compared to conventional oesophageal stents that do not have such an anti-reflux mechanism. Reflux will be measured using patient questionnaires about reflux, and other quality of life parameters, and will also be objectively measured using oesophageal scintigraphy, which has not been used in previous similar trials.
Detailed description
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 presentation. Overall survival remains poor. Management in the South African setting is plagued by late presentation of these patients, with less than 5% being eligible for curative treatment and median survival from the time of diagnosis being only 15 weeks, while those who present with complete obstruction having a median survival of only 75 days (10.7 weeks). Treatment of these patients in the South African setting remains predominantly palliative. The most common and debilitating symptom of advanced oesophageal malignancy is progressive dysphagia, 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 series. Prescribing routine proton pump inhibitors (PPIs) or placing stents with built-in anti-reflux mechanisms are methods aimed at reducing this symptomatic reflux.
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 2019 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. 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, others did not use PPIs in either group, 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 or functional 24-hour pH monitoring. 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. 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.
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 limited 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. Reflux will be assessed subjectively by the administration of patient questionnaires aimed at identifying severity of acid reflux, but also the degree of dysphagia, pain and coughing before and after stent placement. Reflux will also be assessed objectively by using oesophageal scintigraphy performed shortly after stent insertion. Scintigraphy has not previously been used to measure GOR in these patients and is chosen for its accuracy and non-invasive nature (compared to, for example, pH monitoring which requires the placement of an uncomfortable nasal probe for 24 hours and is considered inappropriate in this cohort where the main focus lies on quality of life).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomised to receive either an anti-reflux oesophageal stent or a conventional oesophageal stent.
| Arm | Type | Receives |
|---|---|---|
| Anti-reflux Oesophageal Stent Group (AOSG) | Experimental | Device: Anti-reflux oesophageal stentAll patients randomised to this arm will receive an anti-reflux fully covered self-expanding metal oesophageal stent |
| Conventional Oesophageal Stent Group (COSG) | Active comparator | Device: Conventional oesophageal stentAll patients randomised to this arm will receive a conventional fully covered self-expanding metal oesophageal stent that does not contain an anti-reflux mechanism |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- Patient declining or unable to give informed consent, including inability to speak or understand either English, Afrikaans or isiXhosa (the three most commonly spoken local languages).
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-reflux oesophageal stentFully covered self-expanding metal stent with anti-reflux mechanism | Device | Anti-reflux Oesophageal Stent Group (AOSG) |
| Conventional oesophageal stentFully covered self-expanding metal stent without an anti-reflux mechanism | Device | Conventional Oesophageal Stent Group (COSG) |
Primary outcome
Subjective gastro-oesophageal reflux (GOR) - change in GOR over specified time periods
Time frame: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Self-reported symptomatic reflux using a validated reflux patient questionnaire - the GerdQ questionnaire. GerdQ: score ranges from 0 - 18 points with higher scores equating to higher GOR rates.
Objective gastro-oesophageal reflux (GOR)
Time frame: Will be performed as a once-off investigation on day 1 post stenting
Objective measure of GOR will be done using oesophageal scintigraphy
5 secondary outcomes
Dysphagia - change in dysphagia over specified time periods
Time frame: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Pain - Change in pain over specified time periods
Time frame: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Cough - change in pain over specified time periods
Time frame: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention
Stent-related complications
Time frame: Documentation will occur at the time of stent insertion, day 1 post insertion and then at scheduled follow-ups at weeks 1, 2, 4 and 8 post-insertion or aat any time during the study period if a stent-related complication is reported
Survival
Time frame: Documented at 8 weeks post stent insertion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2022.
- Background: PubMed 31040888Pandit S, Samant H, Morris J, Alexander SJ. Efficacy and safety of standard and anti-reflux self-expanding metal stent: A systematic review and meta-analysis of randomized controlled trials. World J Gastrointest Endosc. 2019 Apr 16;11(4):271-280. doi: 10.4253/wjge.v11.i4.271.
- Background: PubMed 31342677Ferndale L, Sartorius B, Aldous C, Thomson SR. Oesophageal cancer in Area 2 of Kwazulu-Natal: predictors of late presentation. S Afr J Surg. 2019 Jun;57(2):4-9.
- Background: PubMed 31342678Nel 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. S Afr J Surg. 2019 Jun;57(2):10-15.
- Background: PubMed 32998198Ferndale L, Aldous C, Hift R, Thomson S. Gender Differences in Oesophageal Squamous Cell Carcinoma in a South African Tertiary Hospital. Int J Environ Res Public Health. 2020 Sep 28;17(19):7086. doi: 10.3390/ijerph17197086.
- Background: PubMed 25870217Dandara C, Robertson B, Dzobo K, Moodley L, Parker MI. Patient and tumour characteristics as prognostic markers for oesophageal cancer: a retrospective analysis of a cohort of patients at Groote Schuur Hospital. Eur J Cardiothorac Surg. 2016 Feb;49(2):629-34. doi: 10.1093/ejcts/ezv135. Epub 2015 Apr 12.
- Background: PubMed 30684601Dua KS, DeWitt JM, Kessler WR, Diehl DL, Draganov PV, Wagh MS, Kahaleh M, Wong Kee Song LM, Khara HS, Khan AH, Aburajab MM, Ballard D, Forsmark CE, Edmundowicz SA, Brauer BC, Tyberg A, Buttar NS, Adler DG. A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video). Gastrointest Endosc. 2019 Jul;90(1):64-74.e3. doi: 10.1016/j.gie.2019.01.013. Epub 2019 Jan 23.
- Background: PubMed 19737151Jones R, Junghard O, Dent J, Vakil N, Halling K, Wernersson B, Lind T. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1030-8. doi: 10.1111/j.1365-2036.2009.04142.x. Epub 2009 Sep 8.
- Background: PubMed 19968614Blomberg J, Wenger U, Lagergren J, Arnelo U, Agustsson T, Johnsson E, Toth E, Lagergren P. Antireflux stent versus conventional stent in the palliation of distal esophageal cancer. A randomized, multicenter clinical trial. Scand J Gastroenterol. 2010;45(2):208-16. doi: 10.3109/00365520903443860.
- Background: PubMed 27556085Coron E, David G, Lecleire S, Jacques J, Le Sidaner A, Barrioz T, Coumaros D, Volteau C, Vedrenne B, Bichard P, Boustiere C, Touchefeu Y, Bregeon J, Prat F, Le Rhun M; Societe Francaise d'Endoscopie Digestive (SFED). Antireflux versus conventional self-expanding metallic Stents (SEMS) for distal esophageal cancer: results of a multicenter randomized trial. Endosc Int Open. 2016 Jun;4(6):E730-6. doi: 10.1055/s-0042-106960.
- Background: PubMed 15824943Shim CS, Jung IS, Cheon YK, Ryu CB, Hong SJ, Kim JO, Cho JY, Lee JS, Lee MS, Kim BS. Management of malignant stricture of the esophagogastric junction with a newly designed self-expanding metal stent with an antireflux mechanism. Endoscopy. 2005 Apr;37(4):335-9. doi: 10.1055/s-2005-861113.
- Background: PubMed 18410607Sabharwal T, Gulati MS, Fotiadis N, Dourado R, Botha A, Mason R, Adam A. Randomised comparison of the FerX Ella antireflux stent and the ultraflex stent: proton pump inhibitor combination for prevention of post-stent reflux in patients with esophageal carcinoma involving the esophago-gastric junction. J Gastroenterol Hepatol. 2008 May;23(5):723-8. doi: 10.1111/j.1440-1746.2008.05396.x.
- Background: PubMed 17958720Power C, Byrne PJ, Lim K, Ravi N, Moore J, Fitzgerald T, Keeling PW, Reynolds JV. Superiority of anti-reflux stent compared with conventional stents in the palliative management of patients with cancer of the lower esophagus and esophago-gastric junction: results of a randomized clinical trial. Dis Esophagus. 2007;20(6):466-70. doi: 10.1111/j.1442-2050.2007.00696.x.
- Individual participant dataSharing planned: Yes. Individual Participant Data (IPD) that underlie the results reported in the published article for this study, after deidentification, will be made available to any investigator or investigators who request the data for analyses to achieve specific aims of a proposed research study. The study and proposed use of the data must be approved by an independent review committee identified for this purpose. The Study Protocol and Informed Consent Form will also be made available on request. Data will be available immediately after publication of the study and for 5 years after this. Proposals should be directed to matthias.scriba@gmail.com. to gain access, data requestors will need to sign a data access agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias F Scriba, FCS (SA) principal investigator
University of Cape Town
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anti-reflux oesophageal stent and Conventional oesophageal stent in people with Esophageal Cancer and Reflux, Gastroesophageal, run by University of Cape Town at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matthias F Scriba, FCS (SA) (+27 82 295 2611, matthias.scriba@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjective gastro-oesophageal reflux (GOR) - change in GOR over specified time periods (time frame: Will be assessed pre-intervention and then at 1, 2, 4, and 8 weeks post intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05303298, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2022.