Anaphylaxis
Conditions
Brief summary
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.
Interventions
COMBINATION_PRODUCTEpipen 0.3mg
Epipen 0.3mg auto-injector
COMBINATION_PRODUCTEmerade 300mcg
Emerade 300mcg auto-injector
COMBINATION_PRODUCTEmerade 500mcg
Emerade 500mcg auto-injector
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Catecholamine Levels (Maximum Concentration, Cmax) | 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. |
| Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax) | 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. |
| Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC)) | 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
| Measure | Time frame | Description |
|---|---|---|
| Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax) | 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. |
| Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax) | 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. |
| Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC) | 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. |
| Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate) | 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. |
| Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions. | 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. |
| Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume) | 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. |
| Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | 1 day | Adverse events following self-administration of adrenaline via autoinjector device defined as in protocol |
| Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ | 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. |
| Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure) | 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. |
| Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions. | 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. |
| Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions. | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Cohort Overall study cohort | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Overall Cohort | — |
|---|---|---|
| Age, Continuous | 15.4 years | — |
| Body Mass Index | 20 kg/m^2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United Kingdom | 12 participants | — |
| Sex: Female, Male Female | 5 Participants | — |
| Sex: Female, Male Male | 7 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 9 / 12 | 8 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC))
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.
Time frame: At at the following timepoints following injection: 5, 10, 15, 20, 30, 45, 60, 80, 100, 120 and 180 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emerade 300mcg Injection | Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC)) | 174 hr*pg/ml |
| Emerade 500mcg Injection | Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC)) | 387 hr*pg/ml |
| Epipen 0.3mg | Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC)) | 203 hr*pg/ml |
Primary
Plasma Catecholamine Levels (Maximum Concentration, Cmax)
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.
Time frame: 3 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emerade 300mcg Injection | Plasma Catecholamine Levels (Maximum Concentration, Cmax) | 218 pg/ml |
| Emerade 500mcg Injection | Plasma Catecholamine Levels (Maximum Concentration, Cmax) | 394 pg/ml |
| Epipen 0.3mg | Plasma Catecholamine Levels (Maximum Concentration, Cmax) | 290 pg/ml |
Primary
Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax)
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.
Time frame: 3 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emerade 300mcg Injection | Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax) | 9.6 minutes |
| Emerade 500mcg Injection | Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax) | 8.5 minutes |
| Epipen 0.3mg | Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax) | 5.9 minutes |
Secondary
Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device
Adverse events following self-administration of adrenaline via autoinjector device defined as in protocol
Time frame: 1 day
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Emerade 300mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Pain at injection site | 8 Participants |
| Emerade 300mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Systemic AE (any) | 4 Participants |
| Emerade 300mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Palpitations | 3 Participants |
| Emerade 300mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Tremor | 3 Participants |
| Emerade 500mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Tremor | 7 Participants |
| Emerade 500mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Pain at injection site | 6 Participants |
| Emerade 500mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Palpitations | 4 Participants |
| Emerade 500mcg Injection | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Systemic AE (any) | 9 Participants |
| Epipen 0.3mg | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Tremor | 8 Participants |
| Epipen 0.3mg | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Systemic AE (any) | 8 Participants |
| Epipen 0.3mg | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Palpitations | 3 Participants |
| Epipen 0.3mg | Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device | Pain at injection site | 7 Participants |
Secondary
Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Pharmacodynamics (blood pressure) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.
Time frame: 3 hours
Secondary
Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ
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.
Time frame: 1 month
Secondary
Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Pharmacodynamics (heart rate) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.
Time frame: 3 hours
Secondary
Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Pharmacodynamics (stroke volume) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.
Time frame: 3 hours
Secondary
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure)
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.
Time frame: 3 hours
Secondary
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate)
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.
Time frame: 3 hours
Secondary
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume)
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.
Time frame: 3 hours
Secondary
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC)
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.
Time frame: 3 hours
Secondary
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)
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.
Time frame: 3 hours
Secondary
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)
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.
Time frame: 3 hours