Allergy Antibiotics And Microbial Resistance

Study Overview
=================
Brief Summary
-----------------
ALBAMA study is designed to find out if the Penicillin allergy assessment pathway (PAAP) intervention is clinically effective in improving patient health outcomes.

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 asking GPs in West Yorkshire to help with this research, which plans to include 96 people in the initial feasibility study and 1994 people in the main study.

Official Title
-----------------
Penicillin Allergy Status And Its Effect On Antibiotic Prescribing, Patient Outcomes, and Antimicrobial Resistance

Conditions
-----------------
Infection

Intervention / Treatment
-----------------
* Procedure: penicillin allergy assessment pathway


Participation Criteria
=================
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. Patients with a penicillin allergy record and a recent penicillin prescription would still be eligible because their allergy status will need assessment and records correcting if necessary. 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 Previous specialist investigation for penicillin allergy History of brittle asthma (had a course of steroids in the past 3 months) 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 Currently receiving or due to start immunosuppressive medication Currently taking (or recently taken) systemic steroids and unable to stop these for 10 days pretesting. Currently taking antihistamines and unable to stop these for 4 days pre-testing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentre, two parallel-arm, open label, individually randomised pragmatic trial with a nested-pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: penicillin allergy assessment pathway<br>Those in the PAAP intervention arm will complete stage 2&3 of the PAAP pathway: Stage-2 assessed for skin testing (ST) and ST done or straight to stage 3 Stage-3 oral challenge test (OCT) All completing PAAP will receive a letter from the immunology clinic giving the results of the test. Also, patients who have tested negative will receive the Post-test Intervention Booklet and Patient Intervention Card Materials. Additionally, all participants in the PAAP arm will be called by the trial team at days 4-6 and 28-30 post testing to collect safety data. During the call at days 28-30 patients will complete the patient questionnaire on allergy beliefs. Practices will be informed of the test result and instructed to update the participant's electronic health records accordingly. | Procedure: penicillin allergy assessment pathway<br>* Summary of penicillin allergy assessment pathway : Stage-1 PAAP in Primary Care - Clinical History. Screening, questionnaire and antimicrobial history will be undertaken in primary care Stage-2 Skin Test(ST) in hospital clinic (this may not be needed for all participants) Stage 3 Oral Challenge Test (OCT) in hospital clinic Testing will involve half a day in clinic and then a three-day post clinic course of oral antimicrobial therapy, without a reaction<br>* Other names: PAAP;|
| No Intervention: Control Arm<br>The usual care arm receive no intervention but will be followed up as per intervention arm with monitoring of any symptoms following an antibiotic prescription. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response failure | Treatment response failure will be defined as: Re-presentation with worsening or non-resolving symptoms following treatment with an antibiotic up to 28 days after initial antibiotic prescription (including re-prescription of antibiotic within 28 days of an index prescription) for predefined conditions (TPP/notes review), over the year subsequent to randomisation. This will be compared between groups | Measured after first antibiotic prescription, which can occur any time during 12 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom duration | Duration of symptoms (in days) rated 'moderately bad' or worse by patients, after initiation of antibiotic treatment | Up to 28 days after each antibiotic prescription. | 
| Total antibiotic prescribing | Count of total antibiotic use (measured as total number of days therapy and as average daily quantity (ADQ) antibiotics. Total number of penicillin and each non-penicillin antibiotic prescriptions (measured as total number of days therapy and ADQ) | Measured at 12 month post-randomisation | 
| Hospital admissions | Count of total number of hospital admissions | Measured at 12 month post-randomisation | 
| Length of hospital stays | Count of total length of hospital stays | Measured at 12 month post-randomisation | 
| Mortality rates | Mortality rates compared between intervention arms | Measured at 12 month post-randomisation | 
| Meticillin-resistant Staphylococcus aureus (MRSA) infection/ colonisation | Total number of patients with MRSA infection/colonisation compared between intervention arms | Measured 12 month post-randomisation | 
| Clostridium difficile infection | Number of patients with Clostridium difficile infection | Measured 12 month post-randomisation | 
| (Process evaluation) To explore patient and clinician experiences of trial procedures. | GP and patient interviews | Within 12 months of practice recruitment of a proportion of tested patients | 
| To measure changes in clinician and patient behaviour change regarding prescribing and consuming penicillin following a negative test result. | Change in self-reported behaviour by clinicians and patients. | Within 12 months of practice recruitment of a proportion of tested patients | 
| To measure the influences on clinician and patient behaviour change regarding prescribing and consuming penicillin following a negative test result. | influences on behaviour by clinicians and patients. | Within 12 months of practice recruitment of a proportion of tested patients | 
| Cost effectiveness for the PAAP intervention compared to usual care | Measurement of quality adjusted life years in each arm | Collated for period: randomisation to 12 months of randomisation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
penicillin, allergy, antimicrobial, resistance