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Completed

NCT Number: NCT03366298

Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers

Food allergy affects up to 2% of adults and 8% of children in the United Kingdom (UK), and is a major public health issue. It is the commonest cause of life-threatening allergic reactions (anaphylaxis), which can be fatal. Adrenaline (epinephrine) auto-injector (AAI) devices are the first-line treatment for anaphylaxis, yet in a UK survey, over 80% of 245 teenagers experiencing anaphylaxis did not use their AAI. Delays in, or lack of adrenaline (epinephrine) administration during anaphylaxis are risk factors for fatal anaphylaxis.

In 2010, a coroner's investigation into the death of a food-allergic teenager in the UK raised several questions around AAI safety and efficacy, since the teenager died despite administering her auto-injector device. This prompted a review by the Medicines and Healthcare products Regulatory Agency (MHRA) in 2014 into the clinical and quality considerations of AAIs. Two recommendations which came from the review was that companies 'should be encouraged to develop a 0.5mg [dose] AAI.' In the UK currently only Emerade, one of the three companies selling AAIs, manufactures a 0.5mg (500mcg) version. Emerade also has a longer needle length (23mm) compared to other AAIs (typically 15mm).

The investigators plan to formally assess the pharmacokinetics (PK) and pharmacodynamics (PD) of self-injection with intramuscular adrenaline (epinephrine) in teenagers at risk of anaphylaxis due to food allergy, and have been prescribed AAI.

1. The investigators will compare self-injection with 300mcg vs 500mcg in teenagers of body weight >40kg. In a 40kg person, an adrenaline dose of 300mcg results in an effective UNDER-dosing of 30% by body weight. 2. The investigators will also assess the impact of needle length on injection, by comparing two different devices, both of which deliver 300mcg, but one via a 15mm needle and the other with a 23mm needle.

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Key information

Conditions

Anaphylaxis Hypersensitivity Hypersensitivity, Immediate Immune System Diseases

Age range

13 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Imperial College London / Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 13 - 18 years inclusive
  • Body mass >40kg
  • Prescription of AAI due to physician diagnosis of Immunoglobulin E-mediated food allergy.
  • Written informed consent from parent/guardian together with patient assent, for participants under 16 years of age. For young people age 16+ years, consent will be obtained from the participant themselves.

Exclusion criteria

  • Known cardiac comorbidity (including hypertension, structural or electrophysiological diagnoses) or prescribed a medicine to control cardiovascular disease/hypertension.
  • Known endocrine or renal disease
  • Poorly controlled asthma requiring daily rescue treatment with a bronchodilator.
  • Pregnancy
  • Unwilling or unable to comply with study requirements

Treatment and study plan

Epipen 0.3mg

Combination Product

Epipen 0.3mg auto-injector

Other names: Epinephrine

Emerade 300mcg

Combination Product

Emerade 300mcg auto-injector

Other names: Epinephrine

Emerade 500mcg

Combination Product

Emerade 500mcg auto-injector

Other names: Epinephrine

Primary outcomes

  1. Plasma Catecholamine Levels (Maximum Concentration, Cmax)

    Time frame: 3 hours

    Pharmacokinetics (plasma catecholamine levels: Cmax) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  2. Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax)

    Time frame: 3 hours

    Pharmacokinetics (plasma catecholamine levels: Tmax) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  3. Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC))

    Time frame: At at the following timepoints following injection: 5, 10, 15, 20, 30, 45, 60, 80, 100, 120 and 180 minutes

    Pharmacokinetics (plasma catecholamine levels: AUC) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

    Baseline corrected.

Secondary outcomes

  1. Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.

    Time frame: 3 hours

    Pharmacodynamics (heart rate) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  2. Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.

    Time frame: 3 hours

    Pharmacodynamics (blood pressure) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  3. Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.

    Time frame: 3 hours

    Pharmacodynamics (stroke volume) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  4. Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)

    Time frame: 3 hours

    Pharmacokinetics (plasma catecholamine levels: Cmax) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.

  5. Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)

    Time frame: 3 hours

    Pharmacokinetics (plasma catecholamine levels: Tmax) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.

  6. Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC)

    Time frame: 3 hours

    Pharmacokinetics (plasma catecholamine levels: AUC) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.

  7. Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate)

    Time frame: 3 hours

    The pharmacodynamics (cardiovascular parameters: heart rate) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.

  8. Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure)

    Time frame: 3 hours

    The pharmacodynamics (cardiovascular parameters: blood pressure) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.

  9. Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume)

    Time frame: 3 hours

    The pharmacodynamics (cardiovascular parameters: stroke volume) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.

  10. Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device

    Time frame: 1 day

    Adverse events following self-administration of adrenaline via autoinjector device defined as in protocol

  11. Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ

    Time frame: 1 month

    The impact of self-administration of adrenaline autoinjectors (in a non-reaction setting) on health-related quality of life (HRQL) measures in food-allergic teenagers and their parents.

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Registry information

Official study title

Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers: Does Dose Matter?

Acronym: PIMAT

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Dec 8, 2017
Registry last updated
Sep 7, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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