Development of Diagnostic Pathway for Teicoplanin Allergy

Development of a Novel Diagnostic Pathway for Immediate Type Hypersensitivity Reactions to Teicoplanin, Including Invivo and Ex-vivo Testing Modalities.

Teicoplanin is an antibiotic used very commonly to prevent infection during surgery. Its use has expanded rapidly in the last few years, with around 18,500 doses administered in Leeds Teaching Hospitals NHS Trust alone, in 2014-15. Unfortunately, anaphylaxis (a severe allergic reaction) to the drug appears to be increasing. These reactions can result in admission to intensive care, prolong hospital stay, or even be fatal.

It is vital that patients who suffer anaphylaxis have tests to accurately identify the cause, so they can avoid the drug in future. However these tests are currently very limited, because we don't have any diagnostic tools proven to confirm or refute a diagnosis of teicoplanin allergy. We have to make a 'best guess' diagnosis, leaving patients vulnerable to harm in the future, should they require antibiotics again. We need to reliably diagnose teicoplanin allergy to reduce this arm. Where a diagnosis of teicoplanin allergy is confirmed, patients and their doctors know to avoid it. Importantly, where allergy is excluded, teicoplanin can be safely used, avoiding alternatives that may be less effective, more toxic, and more expensive. This directly benefits individuals, saves the NHS money by reducing avoidable harm, and helps improve antibiotic stewardship at a population level - which in the long term helps reduce antibiotic resistance. The clinical need for this work has become imperative.

Collaborating with our industry partner ThermoFisher (significant expertise in this area), we aim to:

1. Standardise the current skin testing protocols being used when testing patients with suspected teicoplanin allergy.
2. Develop laboratory tests to support the skin tests, and give a more confident diagnosis to patients.
3. Understand how and why people develop allergy to teicoplanin, to better predict and modify the allergic response.

Study Overview

• Status: Unknown
• Conditions: Hypersensitivity
• Intervention / Treatment: Procedure: Blood test, skin testing and challenge testing.

• Study Type: Interventional
• Enrollment (Anticipated): 548
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louise Savic, MBBS MRCP FRCA; Phone Number: +44 113 243 3144; Email: louise.savic@nhs.net

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS1 3HE,
    • Recruiting
    • Leeds Teaching Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 98 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All groups >16 years, willing and able to give informed consent.

Group 1(G1). Naïve controls 72 recruited from staff/students of the University of Leeds (n= >40,000 persons) where infrastructure exists to advertise and rapidly recruit

INCLUSION CRITERIA:

• >16 years, willing and able to give informed consent
• Never received teicoplanin

Group 2(G2). "High risk". Received teicoplanin and suffered IgE mediated allergic reaction as defined by our pre-set clinical criteria n=132 to achieve n-119 with complete follow up data, recruited from the "Suspected Anaesthetic Allergy clinic", where patients who have suffered suspected perioperative allergy are referred.

INCLUSION CRITERIA:

• >16 years, willing and able to give consent
• Received teicoplanin and suffered suspected IgE mediated anaphylaxis

Group 3 (G3). "Low risk". Received teicoplanin without reaction

G3: n=397 to achieve n=357 with complete follow up data, recruited from surgical areas where teicoplanin is used routinely; predominantly orthopaedic surgery

Exclusion Criteria:

EXCLUSION CRITERIA for G1, G2 and G3.

• History of antibiotic anaphylaxis/specialist drug allergy testing
• History of toxic epidermal necrolysis or Stevens Johnson syndrome
• Brittle asthma
• Dermographism or other poorly controlled skin condition
• Pregnant, planning to become pregnant during study, breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naive controls; Never received teicoplanin. Blood test, skin testing and challenge testing.	Procedure: Blood test, skin testing and challenge testing.; Skin Prick Testing (SPT) and Intradermal Testing (IDT). We will follow the STARD framework for reporting studies of diagnostic accuracy
Experimental: High Risk; Received teicoplanin and suffered suspected IgE mediated anaphylaxis. Blood test, skin testing and challenge testing.	Procedure: Blood test, skin testing and challenge testing.; Skin Prick Testing (SPT) and Intradermal Testing (IDT). We will follow the STARD framework for reporting studies of diagnostic accuracy
Experimental: Low Risk; Received teicoplanin previously with no adverse reaction Blood test, skin testing and challenge testing.	Procedure: Blood test, skin testing and challenge testing.; Skin Prick Testing (SPT) and Intradermal Testing (IDT). We will follow the STARD framework for reporting studies of diagnostic accuracy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In vivo testing	Skin testing protocols, which identify IgE mediated sensitivity to teicoplanin.	12 months

Collaborators and Investigators

• Sponsor: The Leeds Teaching Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): May 1, 2021

Study Registration Dates

• First Submitted: March 27, 2017
• First Submitted That Met QC Criteria: July 5, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 4, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: AN15/424

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