Antibiotics for uncomplicated lower respiratory tract infection in older adults
| ISRCTN | ISRCTN11309776 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11309776 |
| IRAS number | 1010353 |
| Secondary identifying numbers | ERGO77292, CPMS 56324, NIHR157478 |
- Submission date
- 29/08/2024
- Registration date
- 17/10/2024
- Last edited
- 23/06/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
AFLOAT is a two-arm, double-blinded non-inferiority trial at multiple primary care sites. Non-complicated lower respiratory tract infections (LRTIs) are the most common reason for antibiotic prescription in the UK, despite most infections being viral in origin, to which antibiotics confer no meaningful results. Older people, aged 75+ are prescribed more antibiotics than any other age group in the UK. LRTI was estimated to cost the NHS ≈£190 million in 2005. Older people are at increased risk of a prolonged and more severe illness, development of pneumonia and exacerbation of pre-existing chronic conditions. Whether older patients with risk factors for complications benefit from antibiotics is unknown and NICE guidance recommends considering immediate or delayed antibiotics for this group when presenting with non-complicated LRTIs. This leaves prescribing clinicians with frequent dilemmas over whether to prescribe antibiotics in this patient population. Antibiotic overuse can increase the risk of carriage of antibiotic-resistant organisms, which is a threat both for the individual treated and wider society. Antibiotic prescriptions also lead to the medicalisation of self-limiting illness and double re-consultation rates. However, under-prescription of antibiotics may put older people at increased risk of prolonged and more severe illness and pneumonia. This study will look at whether a placebo is non-inferior to antibiotics. The study assesses whether the duration of illness (time until all symptoms are rated absent or mild) is no worse in those who take placebo versus antibiotics in adults aged 65 years old and over who are seen in primary care with LRTI and risk factors for complications.
Who can participate?
Adult patients aged 65 years old and over with symptoms of uncomplicated LRTI and 1 or more risk factors for complications (aged > 80 years, recent hospital admission, chronic conditions, frailty).
What does the study involve?
Participants will be randomised into the doxycycline arm or matched placebo arm and asked to complete a daily diary for a 28-day follow-up period.
What are the possible benefits and risks of participating?
Benefits not given at time of publication.
There is a risk of potentially worsening of LRTI. As detailed above, patients will be given safety netting information for when to contact their healthcare providers.
Where is the study run from?
University Hospital Southampton, UK
When is the study starting and how long is it expected to run for?
August 2024 to July 2027
Who is funding the study?
NIHR Health Technology Assessment Programme (HTA)
Who is the main contact?
afloat@soton.ac.uk
Contact information
Scientific
Trial Manager, Southampton Clinical Trials Unit (SCTU), Mail point 131, University Hospital Southampton, Tremona Road
Southamton
SO16 6YD
United Kingdom
| Phone | +44 (0)23 8120 5154 |
|---|---|
| a.r.leaper@soton.ac.uk |
Principal Investigator
Aldermoor Surgery, Aldermoor Close
Southampton
SO16 5ST
United Kingdom
| M.Lown@soton.ac.uk |
Public
Central email for Southampton Clinical Trials Unit (SCTU), Mail point 131, University Hospital Southampton, Tremona Road
Southampton
SO16 6YD
United Kingdom
| afloat@soton.ac.uk |
Study information
| Study design | Randomized double-blind parallel-group placebo-controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Efficacy |
| Scientific title | Antibiotics for uncomplicated Lower respiratory tract infection in Older AdulTs |
| Study acronym | AFLOAT |
| Study objectives | Primary objective: To test whether placebo is non-inferior to antibiotics in terms of time until all symptoms are rated mild or absent in the population. Secondary objectives: 1. To compare the effect of placebo vs oral doxycycline antibiotic in terms of deterioration of illness, symptom severity, and healthcare consultations. 2. To undertake a cost consequence analysis of placebo vs oral doxycycline antibiotic. |
| Ethics approval(s) |
Approved 16/10/2024, East Midlands – Nottingham 2 REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8009; nottingham2.rec@hra.nhs.uk), ref: 24/EM/0205 |
| Health condition(s) or problem(s) studied | Medical condition: Non-complicated lower respiratory tract infection Medical condition in lay language: non-complicated chest infection Therapeutic areas: Diseases [C] - Respiratory Tract Diseases [C08] |
| Intervention | Doxycycline 100mg orally for five days. Two tablets on day 1 and one tablet on days 2-5, OR matched placebo. Participants will be randomised using the ALEA Clinical randomisation tool on a 1:1 ratio. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacoeconomic |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Doxycycline Capsules BP 100mg [Doxycycline hyclate] |
| Primary outcome measure | Time until all symptoms (cough, phlegm, shortness of breath, wheeze, blocked or runny nose, chest pain, muscle aches, headaches, disturbed sleep, general feeling of being unwell, fever and interference with normal activities) are rated as “absent” or “mild” (scoring 2 or less on a 0-6 point scale) by patients in their self-reported daily diaries |
| Secondary outcome measures | 1. Deterioration of illness (return to the doctor with a worsening of symptoms, new symptoms or signs, illness requiring hospital admission, or death within four weeks) measured using the self-reported patient diaries, on Days 7, 14, 21 and 28 2. Symptom severity during days 2-4 after the initial consultation (patients tell us that this is the period when their symptoms are worst) measured daily, using the self-reported patient diary 3. Antibiotic consumption over 28 days measured using patient self-reporting in a daily diary 4. Total symptom score over time by a patient measured using self-reporting in a daily diary 5. Personal costs to patients and productivity costs measured using a health economist questionnaire in the patient-reported diary at day 28 6. Health-related quality of life measured using the EuroQol EQ-5D-5L questionnaire on day 0 (day of consent), and then every 7 days until day 28 7. Time until return to usual activities (effect on usual activities rated as ‘no problem’) measured using the health-related quality of life questionnaire ] at baseline, and days 7, 14, 21 and 28 |
| Overall study start date | 27/08/2024 |
| Completion date | 31/07/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Lower age limit | 65 Years |
| Sex | Both |
| Target number of participants | 702 |
| Key inclusion criteria | 1. Age 65 years and over 2. Presenting in primary care with signs and symptoms suggestive of an uncomplicated LRTI, defined as acute cough (rated moderately severe or worse and lasting for 14 days or less), and at least one of the following signs or symptoms: productive cough, rhonchi on auscultation, temperature ≥38oC, dyspnoea 3. One or more of the following risk factors for complicated illness: 3.1. Age 80 or over 3.2. >=1 unplanned hospital admissions in the previous year 3.3. Type 1 or 2 diabetes, chronic cardiovascular disease, chronic lung disease, chronic kidney disease, chronic liver disease, chronic neuromuscular disease 3.4. Clinical frailty score >=4 |
| Key exclusion criteria | 1. Clinical diagnosis of pneumonia 2. A known positive test for a viral respiratory pathogen (e.g. COVID-19 or influenza) during current illness (testing will only occur if part of routine practice) 3. Cough thought to most likely have a non-infective origin (e.g. PE, LVF) 4. Patient needs same-day secondary care assessment or hospital admission 5. Significant impaired immunity, e.g. hematologic malignancy, chronic use of oral steroids (≥5mg prednisolone (or equivalent) per day for 7 days or more), known immunodeficiencies 6. Moderate to severe COPD 7. Hospitalisation in the month before index consultation 8. Antibiotic use for respiratory tract infection in the month before index consultation 9. Tetracycline allergy 10. Patient with bronchiectasis, cystic fibrosis or primary ciliary dyskinesia (not often seen in primary care) 11. Inability to complete the patient diary 12. Taking part in another CTIMP |
| Date of first enrolment | 18/02/2025 |
| Date of final enrolment | 14/03/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Waterlooville, Hampshire
PO8 8DL
United Kingdom
Coker Close
Bicester
OX26 6AT
United Kingdom
Headington
Oxford
OX3 9JA
United Kingdom
Pangbourne
Reading
RG8 7DP
United Kingdom
Reading
RG1 5BS
United Kingdom
Orrysdale Road
West Kirby
Wirral
CH48 5AA
United Kingdom
Vauxhall
Liverpool
L5 8XR
United Kingdom
Blackburn
BB1 6DY
United Kingdom
Kendal, Cumbria
LA9 6SA
United Kingdom
Nettleham
Lincoln
LN2 2RS
United Kingdom
Wellingborough
NN8 4RW
United Kingdom
Holmfirth
HD9 3TP
United Kingdom
Woodland Avenue
Goole
DN14 6RU
United Kingdom
Goodhart Road
Bransholme
Hull
HU7 4DW
United Kingdom
Kenton, Harrow
HA3 9SN
United Kingdom
Durham, County Durham
DH7 0BD
United Kingdom
Colwyn Bay
LL29 7LS
United Kingdom
Rhyl
LL18 1DA
United Kingdom
Wareham
BH20 4PG
United Kingdom
5 James Street
Morecambe
LA4 5TE
United Kingdom
Pontypridd
CF37 2DR
United Kingdom
Sponsor information
University/education
SCTU, Tremona Road
Southampton
SO16 6YD
England
United Kingdom
| Phone | +44 (0)23 8059 5058 |
|---|---|
| afloat@soton.ac.uk | |
| Website | https://www.southampton.ac.uk/ |
"ROR" |
https://ror.org/01ryk1543 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/07/2028 |
|---|---|
| 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. Other publication 4. The data will be published and available in the public domain. Our PPI colleagues will advise on the report to ensure the language is appropriate and accessible. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from afloat@soton.ac.uk |
Editorial Notes
23/06/2025: Oaks Healthcare, Bicester Health Centre, Hedena Health, The Boathouse Surgery, Melrose Surgery, Marine Lake Medical Practice, Vauxhall Health Centre, Shifa Surgery, Station House Surgery, Nettleham Medical Practice, Albany House Medical Centre, Oaklands Health Centre, Bartholomew Medical Group, James Alexander Family Practice, Preston Hill Surgery, The Haven Surgery, West End Medical, Wareham Surgery, Bay Medical Group, Ashgrove Surgery and Clarence Medical Centre were added as study participating centres. The United Kingdom - Wales was added to the countries of recruitment.
28/02/2025: The recruitment start date was changed from 17/02/2025 to 18/02/2025 and the study setting was changed from Hospital to GP practice.
12/02/2025: The recruitment start date was changed from 03/02/2025 to 17/02/2025.
24/01/2025: The recruitment start date was changed from 14/01/2025 to 03/02/2025.
02/12/2024: The following changes were made to the study record:
1. The public title was changed from 'Antibiotics for older adults with non-complicated chest infection' to 'Antibiotics for uncomplicated Lower respiratory tract infection in Older AdulTs'.
2. The scientific title was changed from 'Antibiotics versus placebo for acute lower respiratory tract infection in older adults' to 'Antibiotics for uncomplicated Lower respiratory tract infection in Older AdulTs'.
3. ERGO77292 was added to the secondary identifying numbers.
4. The recruitment start date was changed from 30/10/2024 to 14/01/2025.
5. The recruitment end date was changed from 31/12/2026 to 14/03/2027.
22/10/2024: The ethics approval was added.
29/08/2024: Study's existence confirmed by Health Research Authority (HRA) (UK).
