Clinical trial NCT04108637: Allergy Antibiotics And Microbial Resistance
Official title: Penicillin Allergy Status And Its Effect On Antibiotic Prescribing, Patient Outcomes, and Antimicrobial Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infection
Keywords: penicillin
allergy
antimicrobial
resistance
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2019-09-30
Enrollment: 823
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, two parallel-arm, open label, individually randomised pragmatic trial with a nested-pilot study
Primary purpose: SCREENING

Brief summary: ALBAMA study is designed to find out if the effects of Penicillin allergy assessment pathway (PAAP) intervention is on penicillin prescribing

Detailed description: * Antibiotics are important medicines for fighting infections caused by bacteria. Their widespread use has caused a worrying rise in antibiotic resistant bacteria, which are bacteria that are harder to control or kill with antibiotics. Patients with infections caused by antibiotic resistant bacteria are often ill for longer and have an increased risk of serious harm, including death. The spread of resistant bacteria can be slowed down by using antibiotics more carefully. Penicillins are an important group of antibiotics that are recommended treatment for many infections. Doctors will avoid prescribing penicillin for their patients who have a "penicillin allergy label" in their health records. These patients are usually prescribed different types of antibiotics for their infections. There is concern that these non-penicillin antibiotics may not work as well as penicillins, may cause more side-effects (including killing more of the body's "helpful" bacteria), and may be more expensive.
* About 9 out of 10 people who have a record of penicillin-allergy are found to be not truly allergic to penicillin when thoroughly tested. This means they could safely take penicillins. The aim of ALABAMA is to find out if people with a penicillin-allergy record in their GP health records really do have an allergy by carrying out specialist testing, and to see if it is possible to reduce the number of patients wrongly labelled as penicillin allergic. The investigators will find out if this results in better use of antibiotics and fewer days of symptoms, when patients are prescribed antibiotics for infection.
* The investigators are recruiting up to 140 GP practices in Yorkshire and Humber and the South West Peninsula to help with this research, and plans to include up to 1060 people.

Eligibility criteria: Inclusion Criteria:

* Participant is willing and able to give informed consent for participation in the study
* Male or Female, aged 18 years or above
* Current penicillin allergy (or sensitivity) record of any kind in their electronic health record
* Receipt of either: penicillin, cephalosporin, tetracycline, quinolone or macrolide class antibiotic or fosfomycin, nitrofurantoin, trimethoprim, clindamycin in the previous 12 months

N.B.1 Patients who have been formally tested for penicillin allergy in the past and been found not to be penicillin allergic but still have a medical record indicating a penicillin allergy, are eligible for the trial.

Exclusion Criteria:

* Life expectancy estimated \<1 year by GP

  * Unable to attend immunology clinic
  * Unsuitable for entry into testing pathway because:

    * Allergy history consistent with anaphylaxis to penicillin
    * History of toxic epidermal necrolysis, Stevens-Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS) or any severe rash which blistered or needed hospital treatment, and acute generalised exanthematous pustulosis precipitated by a penicillin
    * Has been formally tested for penicillin allergy in the past and been found to be penicillin allergic
    * History of brittle/severe asthma or has had a course of steroids in the past 3 months for asthma or unstable coronary artery disease, or dermographism or other severe/poorly controlled skin conditions
    * Considered unsuitable for trial participation by the GP e.g. because of chaotic lifestyle
  * Pregnant
  * Breastfeeding mothers
  * Taking beta blocker medication, and unable to temporarily withhold these on the day of penicillin allergy testing
  * Currently taking (or recently taken) systemic steroids and unable to stop these for 10 days pretesting.
  * Currently taking antihistamines and unable to temporarily withhold these for 72 hours pre-testing

GPs may also want to exclude vulnerable patients who are deemed to be unsuitable to participate for other reasons such as, but not limited to, terminal illness, reliability, mental illness, learning difficulties, anxiety, and other family circumstances.

N.B.1 Patients that are currently taking medicines with antihistamine properties that cannot be temporarily withheld, or patients with isolated dermographism, may still be eligible to participate but will need to be discussed with the research team prior to consent.

N.B.2 Pregnancy and breastfeeding exclusion criteria are only applicable at screening (due to potential risks of PAT); these patients would not need to be withdrawn if in follow up.

Primary outcomes:
measure: Penicillin prescribing
timeFrame: Measured at up to 12 month post-randomisation
Secondary outcomes:
measure: Treatment "response failure"
timeFrame: Measured after first antibiotic prescription, which can occur any time during the follow-up period for patients(Up to 12 months post randomisation)
measure: Symptom duration
timeFrame: Measured up to 12 month post-randomisation
measure: Total antibiotic prescribing
timeFrame: Measured up to 12 month post-randomisation
measure: Hospital admissions
timeFrame: Measured up to 12 month post-randomisation
measure: Length of hospital stays
timeFrame: Measured up to 12 month post-randomisation
measure: Mortality rates
timeFrame: Measured up to 12 month post-randomisation
measure: Meticillin-resistant Staphylococcus aureus (MRSA) infection/ colonisation
timeFrame: Measured up to 12 month post-randomisation
measure: Clostridium difficile infection
timeFrame: Measured up to 12 month post-randomisation
measure: (Process evaluation) To explore patient and clinician experiences of trial procedures.
timeFrame: Within 12 months of practice recruitment of a proportion of tested patients
measure: To measure changes in clinician and patient behaviour change regarding prescribing and consuming penicillin following a negative test result.
timeFrame: Within 12 months of practice recruitment of a proportion of tested patients
measure: To measure the influences on clinician and patient behaviour change regarding prescribing and consuming penicillin following a negative test result.
timeFrame: Within 12 months of practice recruitment of a proportion of tested patients
measure: Cost effectiveness for the PAAP intervention compared to usual care
timeFrame: Collated for period: randomisation to up to 12 months of randomisation
measure: De-labelling
timeFrame: check performed at 3 and 12 months
Other outcomes:
measure: AEs and SAEs reported
timeFrame: Measured at up to 12 month post-randomisation
measure: Effects of PAAP on all outcomes for follow up past 12 months
timeFrame: Measured at the end of the study
Locations:
city: York
country: United Kingdom
facility: NIHR CRN: Yorkshire and Humber
Study officials:
affiliation: University of Leeds
name: Jonathan Sandoe, Dr
role: STUDY_CHAIR
References: