Allergy Antibiotics And Microbial Resistance (ALABAMA)

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

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

Study Overview

• Status: Completed
• Conditions: Infection
• Intervention / Treatment: Procedure: penicillin allergy assessment pathway

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.

• Study Type: Interventional
• Enrollment (Actual): 823
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • York, United Kingdom, S10 2SB
    • NIHR CRN: Yorkshire and Humber

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Penicillin prescribing	The proportion of participants who receive prescriptions for a penicillin when attending for predefined conditions where a penicillin is the first-line recommended antibiotic	Measured at up to 12 month post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(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
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 the follow-up period for patients(Up to 12 months post randomisation)
Symptom duration	Duration of symptoms (in days) rated 'moderately bad' or worse by patients, after initiation of antibiotic treatment	Measured up to 12 month post-randomisation
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 up to 12 month post-randomisation
Hospital admissions	Count of total number of hospital admissions	Measured up to 12 month post-randomisation
Length of hospital stays	Count of total length of hospital stays	Measured up to 12 month post-randomisation
Mortality rates	Mortality rates compared between intervention arms	Measured up to 12 month post-randomisation
Meticillin-resistant Staphylococcus aureus (MRSA) infection/ colonisation	Total number of patients with MRSA infection/colonisation compared between intervention arms	Measured up to 12 month post-randomisation
Clostridium difficile infection	Number of patients with Clostridium difficile infection	Measured up to 12 month post-randomisation
Cost effectiveness for the PAAP intervention compared to usual care	Measurement of quality adjusted life years in each arm	Collated for period: randomisation to up to 12 months of randomisation
De-labelling	The proportion of ALABAMA participants whose labels were removed and remain removed from the medical eHR	check performed at 3 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs and SAEs reported	A descriptive analysis will be performed looking at the safety (number of AEs and SAEs) of de-labelling in the intervention group	Measured at up to 12 month post-randomisation
Effects of PAAP on all outcomes for follow up past 12 months	Descriptive analysis using data captured in the notes review CRF	Measured at the end of the study

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: University of Oxford
• Investigators: Study Chair: Jonathan Sandoe, Dr, University of Leeds

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2019
• Primary Completion (Actual): February 29, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: June 4, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: antimicrobial; allergy; resistance; penicillin
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Anti-Infective Agents; Anti-Bacterial Agents; Penicillins
• Other Study ID Numbers: V14.0 16Nov2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No