Can better tests improve the right use of antibiotics in respiratory infections?

ISRCTN	ISRCTN35745418
DOI	https://doi.org/10.1186/ISRCTN35745418
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	246355
Sponsor	NHS Lothian
Funder	Chief Scientist Office

Submission date: 22/05/2019
Registration date: 18/07/2019
Last edited: 18/07/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
There is an international drive to simplify antibiotic treatments to stop side effects from antibiotics and to stop the development of superbugs.
Pneumonia is an infection of the lung affecting 5 to 11 people out of 1,000 in the population. About 9% of patients admitted to hospital with pneumonia will die. Prompt and appropriate antibiotic treatment is needed to cure the pneumonia. International guidelines suggest using a combination antibiotic treatment for 7 to 10 days for patients admitted with pneumonia. However it is not completely known what antibiotics to prescribe or for how long antibiotic treatment is needed.
By the time patients are admitted to hospital with pneumonia many of them will already have had antibiotic therapy by their GPs. This can limit the results from standard pneumonia investigations. Tests currently used in the NHS can identify the cause of pneumonia in only 39% of patients. In addition, traditional methods to investigate pneumonia in the NHS take too long to give an answer. In many cases clinicians do not have enough information to confidently shorten or reduce antibiotic treatments.
We have developed a molecular test that identifies the cause of pneumonia in 87% of patients. Our test still works even if the patient has already started antibiotic treatment. Our test is very quick and we can have a result within a few hours. We call our test a "MICAP" molecular investigation of community acquired pneumonia.
The main aim of the study is to determine if the PIB CAP test can reduce the amount of antibiotics prescribed without any undesirable clinical side effects. We will count up how much antibiotic treatment each participant had, including any additional antibiotics that might have been needed after initial treatment.

Who can participate?
Any patient at the hospital over 18 years of age who has three or more of the symptoms of lower respiratory tract infection can participate.

What does the study involve?
We will invite patients who have been admitted to hospital with lower respiratory tract infection to enrol onto our study. We will use a computer program to randomly decide which test participants will have. Half the participants will have the usual NHS tests and will receive the normal treatment for pneumonia. The other half of participants will have our molecular test and the results will customise their antibiotic treatment. We estimate that we will need to enrol 600 participants to the study in order to detect any differences between the group receiving standard NHS treatment and the group receiving customised antibiotic treatment. After 30 days each participant will have medical examinations and tests to see if it is safe to treat pneumonia with less antibiotics. We will also calculate if personalised antibiotic therapy is cost-effective for the NHS compared to the current treatment.

What are the possible benefits and risks of participating?
Benefits: guide to the best treatment for infection and limit the antibiotics to only those that are required for treatment
Risk: antibiotics that are not specific for treatment may have a benefit and these would not be provided to those taking part in the study

Where is the study run from?
Royal Infirmary of Edinburgh, UK.

When is the study starting and how long is it expected to run for?
June 2019 to June 2021

Who is funding the study?
Chief Scientist Office, Division Scotland

Who is the main contact?
Dr Kate Templeton,
kate.templeton@ed.ac.uk

Contact information

Dr Kate Templeton
Public

Deparmtment of Medical Microbiology
Royal Infirmary
Edinburgh
EH16 4SA
United Kingdom

ORCID ID	0000-0001-7414-1277
Phone	0131 242 6015
Email	kate.templeton@ed.ac.uk

Study information

Primary study design	Interventional
Study design	Single centre randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Measuring the impact of improved diagnostics on antimicrobial stewardship in respiratory tract infection (MIDAS Study)
Study acronym	MIDAS
Study objectives	The MICAP assay to diagnose the aetiological agents in CAP and LRTI will have a result within 36 hours of hospital admission and give personalised targeted antibiotic treatment safely reducing the antibiotic burden or giving the appropriate antibiotic based on the pathogen identified.
Ethics approval(s)	Approved 24/08/2018 South East Scotland REC 1 (NHS Lothian, Waverley Gate, 2 - 4 Waterloo Place, Edinburgh, EH1 3EG; 0131 465 5473; Sandra.Wyllie@nhslothian.scot.nhs.uk), ref: 18/SS/0093, IRAS ID 246355
Health condition(s) or problem(s) studied	Pneumonia, Lower respiratory tract infection
Intervention	Study arm (intervention arm) – patient sputum sample will be tested by rapid pneumonia assay (MICAP) and then have treatment guided in response to results. The treatment guidance is as per standard treatment based on NHS Lothian guidelines (available at https://www.ljf.scot.nhs.uk/LothianJointFormularies/Adult/5.0/(b)/Pages/default.aspx) The control arm – receive standard microbiology investigations and treatment in accordance with NHS Lothian guidance.
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	To explore whether participants admitted with LRTI can safely receive personalised antibiotic therapy within 12 hours of consent for this test on existing sputum sample assessed by review of patient notes.
Key secondary outcome measure(s)	1. CAP resolution at days 7 and 30 (Y/N) 2. Major adverse events (Y/N) and number. Major adverse events = complicated parapneumonic effusion, empyema, lung abscess, vascular event (acute coronary syndrome or cerebrovascular accident) or antibiotic-associated C. difficile, need for inotropic support, non-invasive or invasive ventilation or another major adverse event reported by the clinician and confirmed by the adjudication committee 3. Readmissions to hospital within 30 days due to LRTI 4. Death (at 30 days and time to death) 5. Narrowing spectrum of antibiotics assessed by drug chart for antibiotics given daily from date of consent 6. Macrolide DDD assessed by drug chart for antibiotics given daily from date of consent 7. Alteration or addition of antibiotic therapy assessed by drug chart for antibiotics given daily from date of consent 8. Length of hospital stay assessed by date of admission to date of discharge. Recovered for hospital records 9. Antibiotic side effects measured from date of consent assessed by notes of side effects attributed to antibiotics in clinical notes 10. Antibiotic costs assessed by costs from Pharmacy unit of current drug costs for the course given 11. Patient symptoms assessed using a pneumonia specific questionnaire 12. Antibiotic resistance in bacteria isolated assessed by MICs of bacteria isolated, resistance markers via molecular methods for bacteria detected by PCR 13. Assess the optimum specimen(s) for assessment of LRTI for bacteria, atypical bacteria and Viruses assessed by comparison of PCR results with sputum to throat swab where they exist 14. Cost per Quality-Adjusted Life Year at 30 days 15. Cost per DDD of antibiotics at 30 days
Completion date	01/06/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	600
Key inclusion criteria	1. Aged 18 and over 2. Hospitalised 3. Lower respiratory tract specimen taken for routine microbiology within 48 hours of admission and - 3 or more of following signs or symptoms of respiratory tract infection: -new or worsening cough -new or worsening expectoration of sputum -haemoptysis -new or worsening dyspnea -pleuritic chest pain -fever -headache -abnormalities on chest auscultation or percussion
Key exclusion criteria	1. Hospitalisation for more than 48 hours 2. No capacity to consent 3. Active malignancy 4. Immunodeficiency - defined as being on long term (˃28 days) oral prednisolone 10mg or more per day or other long term disease modifying drug 5. Solid organ transplant 6. All forms of pulmonary fibrosis including usual interstitial pneumonia, asbestosis, non-specific interstitial pneumonia, hypersensitivity pneumonitis, active sarcoidosis 7. Palliative treatment only 8. Mechanical ventilation 9. End of life care 10. Previously randomised into this trial 11. Participation in another CTIMP or CIMD interventional study
Date of first enrolment	22/07/2019
Date of final enrolment	31/01/2021

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

Royal Infirmary of Edinburgh

51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Stored in repository
IPD sharing plan	The datasets generated during and/or analysed during the current study will be stored in a publically available repository (http://www.edinburghlabmed.co.uk/ClinicalResearch/Pages/default.aspx).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			26/07/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

18/07/2019: Trial’s existence confirmed by Lothian NHS board