ALABAMA: Allergy Antibiotics And Microbial Resistance

Sponsor

University of Leeds (Other)

Overall Status

Recruiting

CT.gov ID

NCT04108637

Collaborator

University of Oxford (Other)

2,090

Enrollment

Location

Arms

46.9

Anticipated Duration (Months)

44.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infection	Procedure: penicillin allergy assessment pathway	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2090 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicentre, two parallel-arm, open label, individually randomised pragmatic trial with a nested-pilot studyMulticentre, two parallel-arm, open label, individually randomised pragmatic trial with a nested-pilot study

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

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

Actual Study Start Date :

Jul 4, 2019

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

May 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: penicillin allergy assessment pathway 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 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 Other Names: PAAP
No Intervention: Control Arm 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.

Arm

Intervention/Treatment

Experimental: penicillin allergy assessment pathway

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

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

Other Names:

PAAP

No Intervention: Control Arm

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.

Outcome Measures

Primary Outcome Measures

Treatment "response failure" [Measured after first antibiotic prescription, which can occur any time during 12 month follow-up]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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