Trial of alginates in throat symptoms
| ISRCTN | ISRCTN13949559 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13949559 |
| EudraCT/CTIS number | 2022-001449-19 |
| IRAS number | 1006014 |
| Secondary identifying numbers | 10037, IRAS 1006014, CPMS 53492 |
- Submission date
- 20/09/2022
- Registration date
- 04/11/2022
- Last edited
- 10/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Ear, Nose and Throat
Plain English summary of protocol
Background and study aims
Persistent throat symptoms (PTS), including hoarse voice, sore throat, feeling of a lump in the throat, throat clearing, mucus going from the nose into the throat and/or catarrh (a build-up of mucus) are very common. At least 60,000 new patients are referred to NHS Ear Nose and Throat (ENT) and/or Speech and Language Therapy (SaLT) departments with PTS each year in the UK.
Specialists think that PTS can be linked to gastroesophageal reflux disease (GORD). GORD happens when the stomach contents (including stomach acid) frequently flow into the oesophagus (the food pipe) which connects the mouth to the stomach. This results in the lining of the oesophagus becoming irritated causing symptoms. The two main treatments for GORD are proton pump inhibitors (PPIs) (which reduce the amount of stomach acid) and liquid alginates (which form a barrier on top of stomach contents to prevent them from leaving the stomach and also act to make the stomach contents less harmful).
A previous trial (TOPPITS) looked at treating PTS with PPIs. This trial found that PPIs are not an effective treatment for PTS as they were only as good as a placebo (a dummy medicine) in treating PTS symptoms. The TALGiTS trial will look at whether liquid alginates are effective in the treatment of PTS. The liquid alginate used is Gaviscon Advance.
Who can participate?
Adults with PTS
What does the study involve?
ENT and SaLT department referral letters for patients presenting with PTS will be reviewed and potentially eligible patients approached for the trial. Participants will take part in the trial for 8 weeks while they are awaiting their routine appointment for their PTS. Participants will be randomised by computer to receive either Gaviscon Advance or a placebo medication (dummy drug), participants and local hospital staff will not know which treatment is allocated. There will be 5 contacts through the trial; one telephone consultation with a member of the trial team, three online questionnaires and one face-to-face clinic appointment.
What are the possible benefits and risks of participating?
Due to the remote nature of the trial, there is the potential to miss any adverse events occurring. To minimise this, every 2 weeks participants will complete a self-report of any illnesses/side effects experienced and any new regular medication that they have started taking.
Participants will be supplied with a Safety Card with the contact details of the Chief Investigator on it, participants are advised to show this card to any care team they interact with to highlight their trial involvement.
The Head and Neck Risk Calculator will be used to determine the risk that patients presenting symptoms are potentially related to cancer. Patients identified as high risk will be excluded from the trial and diverted to standard care urgent referral. Patients meeting the moderate and low-risk criteria are eligible for the trial. For moderate risk, a week 6 appointment is recommended, by participating in the trial patients will be seen at 8 rather than 6 weeks. This is thought acceptable as in standard care the week 6 appointment is a recommendation rather than a target-driven requirement and is not likely routinely met. Trial participation ensures a week 8 appointment, which may be faster than standard care, and does not introduce additional risk for the small number of patients who may subsequently be diagnosed with cancer (estimated 0.9-3%).
As it's not known whether Gaviscon Advance is an effective treatment for persistent throat symptoms (PTS), it is also now known if the participants taking the placebo will experience PTS symptoms deteriorating or lasting longer than if taking the active medication. Use of a placebo is considered acceptable as in standard care no treatment would be given routinely while awaiting a consultation for PTS referral. The Patient Information Sheet (PIS) contains information on the chance of receiving a placebo.
The placebo for the trial is near matched rather than identical. A placebo for Gaviscon Advance that is gloopy, does not adhere to/protect oesophageal mucosa, and whose peppermint flavour does not reduce heartburn is a challenge. Reckitt has developed a placebo for Gaviscon Advance which is indistinguishable in appearance (colour, viscosity, opalescence), odour and taste, however, the mouthfeel is slightly different resulting in the placebo being near-matched rather than identical. Due to the trial's parallel design, remote delivery and the blinding used there is a very low risk that the small difference in mouth feel of the placebo will break the blind.
Gaviscon Advance and other alginate products are available to purchase over the counter and may be accessed/taken by trial participants in addition to their trial treatment. Over-the-counter alginate products will be concomitant medications for the trial, this is clearly indicated in the PIS.
Taking part in the trial will require a time commitment from participants. The trial will last for 8 weeks and has been designed to be delivered mostly in a remote format i.e. without the need for participants to regularly visit the trial hospital site. There are two telephone consultations and one face-to-face consultation with the site trial team scheduled over the 8 weeks. Additionally, participants will be asked to complete questionnaires online at 2, 4 and 6 weeks, these will be able to be completed at a time suitable for participants. Sites will be able to use any contact method, in line with their local policies and procedures, to contact participants remotely. For participants not able to, or not wishing to, complete follow-ups in the suggested format that the format be changed i.e. participants not wanting remote contact are able to attend in person.
Trial medication will be delivered to participants by courier in one shipment at the start of the trial and will contain all of the medication required for the 8 weeks of trial treatment. There is the risk that trial medication does not get received by the participant, e.g., they miss the courier. To prevent this the site trial team will communicate the expected delivery date with participants so that they know when to expect medication. Additionally, participants can nominate the address that they would like the medication delivered or nominate someone else in their household to receive medication on their behalf. If no one appropriate is available, the courier will return the medication to the central distribution centre and re-delivery attempted another day.
Trial medication is supplied in one 'kit' of multiple glass bottles. There is the risk that there may be damage to medication bottles either in transit or after participant receipt. To mitigate this risk, each medication kit includes additional medication that is needed for the 8 weeks of trial treatment.
Where is the study run from?
Newcastle University (UK)
When is the study starting and how long is it expected to run for?
August 2022 to April 2025
Who is funding the study?
Reckitt (UK)
Who is the main contact?
Mr James O’Hara
TALGiTS@newcastle.ac.uk
Contact information
Scientific
Population Health Sciences Institute
Faculty of Medical Sciences
Newcastle University
Newcastle upon Tyne
NE2 4AX
United Kingdom
| Phone | (+44) 0191 2137625 |
|---|---|
| TALGiTS@newcastle.ac.uk |
Principal Investigator
Population Health Sciences Institute
Faculty of Medical Sciences
Newcastle University
Newcastle upon Tyne
NE2 4AX
United Kingdom
 ORCID ID |
0000-0002-4096-3296 |
|---|---|
| Phone | +44 (0)191 2137625 |
| james.o'hara@newcastle.ac.uk |
Public
TALGiTS Trial Management Team
Newcastle Clinical Trials Unit
1-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom
| Phone | +44 (0)191 208 2522 |
|---|---|
| TALGiTS@newcastle.ac.uk |
Study information
| Study design | Randomized multicentre placebo-controlled double-blind parallel-group study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | https://research.ncl.ac.uk/talgits/patient%20information%20sheet/ |
| Scientific title | A pragmatic, multicentre, placebo-controlled, double-blind, parallel, randomised controlled trial of liquid alginate (Gaviscon Advance) for the treatment of persistent throat symptoms |
| Study acronym | TALGiTS |
| Study objectives | The overarching objective of the trial is to investigate whether liquid alginate (Gaviscon Advance) is an effective treatment for persistent throat symptoms. The primary objective of the trial is to compare the symptomatic response in patients with persistent throat symptoms to liquid alginate (Gaviscon Advance) compared to a placebo. The will be measured at the end of the 8-week trial treatment period using a patient-completed Total Reflux Symptom Index questionnaire. 1. To assess symptom responses between the two treatment groups using an additional comprehensive patient-reported outcome measure. Measured at 8 weeks using the Comprehensive Reflux Symptom Score (CReSS) questionnaire and subscales (oesophageal, upper airway and pharyngeal) of the Reflux Index (RSI) questionnaire. 2. To assess symptom responses between the two treatment groups to determine the optimal length of treatment. Measured at 2, 4 and 6 weeks using the patient completed RSI questionnaire. 3. To assess compliance with trial medication. Measured by patient-reported medication levels at 2, 4, 6 and 8 weeks. 4. To assess participants' views of which medication they received. Measured by the direct question at 8 weeks. 5. To assess participant satisfaction with the trial. Measured by direct question and satisfaction questionnaire at 8 weeks. |
| Ethics approval(s) | Approved 04/11/2022, East Midlands – Leicester South Research Ethics Committee (Equinox House, City Link, Nottingham, NG2 4LA, UK; +44 (0)207 104 8193 or (0)207 104 8177; leicestersouth.rec@hra.nhs.uk), ref: 22/EM/0205 |
| Health condition(s) or problem(s) studied | Persistent throat symptoms |
| Intervention | Patients that have been referred to the Ear, Nose and Throat or Speech and Language Therapy department will be invited to take part in the trial and if interested in taking part will be consented remotely and assessed for eligibility. If patients are deemed eligible they will be randomised via sealed envelope to one of two arms: 1. Gaviscon Advance Arm – 8-week treatment period – 10 ml administered orally taken four times daily after meals and before bedtime 2. Placebo Arm – 8-week treatment period - 10 ml administered orally taken four times daily after meals and before bedtime Participants will be sent questionnaires electronically, and report any new medications they may start taking and any adverse events every two weeks. At the end of the treatment period, participants will attend their clinic appointment and complete the final trial questionnaires. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Alginate |
| Primary outcome measure | Participant-reported symptoms measured using the Reflux Symptom Index (RSI) questionnaire at the end of 8 weeks of treatment with liquid alginate (Gaviscon Advance) or placebo |
| Secondary outcome measures | 1. Participant-reported symptoms measured using the Reflux Symptom Index (RSI) questionnaire subscales and the Comprehensive Reflux Symptom Score (CReSS) questionnaire at the end of 8 weeks of treatment with liquid alginate or placebo 2. Participant-reported symptoms measured using the RSI questionnaire with and without heartburn at 2, 4 and 6 weeks of treatment with liquid alginate or placebo 3. Patient-reported trial medication compliance measured by counting patient-reported medication levels at the end of 8 weeks of trial treatment 4. Participant view of trial treatment received measured by the direct question at the end of 8 weeks of trial treatment 5. Participant-reported satisfaction with the trial measured by direct question and satisfaction questionnaire at the end of 8 weeks of trial treatment |
| Overall study start date | 12/08/2022 |
| Completion date | 30/04/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 250 |
| Key inclusion criteria | 1. Aged 18 years old and over 2. ≥ 6-week history of persistent throat symptoms (hoarse voice, lump in throat sensation, throat clearing, cough, post-nasal secretions/catarrh, throat discomfort) as evidenced by a total RSI score omitting the ninth item (heartburn symptoms [HB] “heartburn, chest pain, indigestion or stomach acid coming up” – i.e., RSI – HB) ≥ 13 3. Ability to comprehend trial information and complete trial questionnaires 4. Willing and able to provide informed consent prior to any trial procedures taking place |
| Key exclusion criteria | 1. Any symptoms that meet the NICE guidance for a two-week wait for suspected head and neck cancer referral, i.e., persistent unexplained hoarseness or unexplained neck lump. 2. Any symptoms that when entered into the head and neck cancer risk calculator (ORLHealth.com | HaNC-RC v2, 2019) lead to a recommended urgent suspected cancer referral 3. Prior to the screening, intake of: 3.1. Systemic glucocorticosteroids within 28 days of screening 3.2. Prokinetics (e.g., cisapride) or drugs with prokinetic function, such as macrolide antibiotics, during the preceding 5 days and initiated in the previous 2 weeks of screening 3.3. Anticholinergic drugs, sucralfate or any other drugs that in the investigator’s opinion may affect the baseline measurements for the patient within 7 days of screening 4. Female participants with a known pregnancy 5. Known chronic kidney diseases. Patients with a history of chronic kidney disease will be specifically asked about: reduced kidney function, controlled potassium diet, hypophosphatemia, phenylketonuria, hypercalcaemia, nephrocalcinosis, recurrent calcium containing renal calculi 6. Patients with known or suspected hypersensitivity to the active substances (sodium alginate, potassium hydrogen carbonate), or active substance excipients (methyl parahydroxybenzoate (E128), propyl parahydroxybenzoate (E216), sodium hydroxide, saccharin sodium, carbomer, calcium carbonate) or placebo excipient ingredients (hydrogenated glucose syrup, xanthan gum, titanium dioxide, caramel) 7. Administration of an Investigational Medicinal Product within 30 days of the first dose of IMP 8. Any current or prior head and neck or gastroesophageal malignancy 9. Current or prior malignancy not in complete remission within 3 years of screening with the exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix 10. Inability, in the opinion of the investigator, to be able to complete the clinical trial visits or procedures 11. Any condition that, in the opinion of the investigator, would exclude the patient from participation in the trial |
| Date of first enrolment | 26/05/2023 |
| Date of final enrolment | 30/04/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Sponsor information
Hospital/treatment centre
C/o Chris Price
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
England
United Kingdom
| Phone | +44 (0)191 208 2522 |
|---|---|
| christopher.price6@nhs.net | |
| Website | https://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Reckitt Benckiser Pharmaceuticals, Inc., Reckitt Benckiser Pharmaceuticals Inc, Reckitt Benckiser Pharmaceuticals Limited, RBP
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/04/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Conference presentation 3. Publication on a website 4. Submission to regulatory authorities Participants will be asked to consent to the sharing of anonymised trial data with other researchers, research groups and organisations |
| IPD sharing plan | Data from this trial will be available to the scientific community subject to request and appropriate ethical approval. Requests for data should be directed to the Chief Investigator and Newcastle Clinical Trials Unit. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 08/01/2025 | 10/01/2025 | Yes | No |
Editorial Notes
10/01/2025: Publication reference added.
19/09/2024: IPD sharing plan added.
05/06/2023: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/01/2023 to 26/05/2023.
2. The recruitment end date was changed from 01/11/2024 to 30/04/2025.
02/12/2022: Internal review.
04/11/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 04/11/2022
22/09/2022: Trial's existence confirmed by the HRA.
