The Effect of Antihypertensive Drugs on Severity of Anaphylaxis and Side-effects During Venom Immunotherapy (EADOAS)

There is an ongoing debate whether antihypertensive treatment with beta-blockers and/or angiotensin converting Enzyme (ACE)-inhibitors comprises a risk factor for more severe and more frequent side-effects during venom immunotherapy (VIT). In the literature, data are controversial and originate from case reports or statistically underpowered studies; the number of included patients was usually high but the proportion of patients on antihypertensive treatment was low ranging from 2-11%.

The study was conducted as a prospective, observational, European multicenter study. 1425 patients, aged from 35 to 85 years, with a history of an anaphylactic reaction due to bee or wasp stings, were included. The medical history was recorded as well as laboratory parameters and data of the VIT-updosing phase. One year after reaching the maintenance dose, possible side-effects during VIT as well as the outcome of field stings or sting challenges were documented.

Study Overview

• Status: Completed
• Conditions: Hymenoptera Venom Allergy; Antihypertensive Treatment
• Intervention / Treatment: Drug: Insect Venom

• Study Type: Observational
• Enrollment (Actual): 1425

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Department of Dermatology and Venerology, Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients with a history of anaphylactic sting reaction

Description

Inclusion Criteria:

• History of systemic sting reaction (≥ grade I according the classification by Ring and Messmer)
• age 35 to 85 years

Exclusion Criteria:

• absolute contraindications for VIT
• pretreatment with Omalizumab

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

patients with a history of an anaphylactic sting reaction; At Visit 1, patients will be included after carefully reviewing all inclusion and exclusion criteria. All data concerning the index sting, laboratory parameters like immunoglobulin E (IgE) and tryptase levels and skin test results will be recorded as well as the concomitant diseases and medication. Visit 2 will be performed after VIT updosing is finished. At this Visit data concerning the immunotherapy - premedication, preparation, updosing protocol, the outcome of possible large, local reactions (LLR) and systemic reactions (SR) and changes in diseases and medication will be recorded. One year after reaching the maintenance dose, Visit 3 will be performed. At this Visit data concerning the maintenance phase like premedication and possible side effects will be recorded as well as the outcome of insect stings.

Drug: Insect Venom; Patients receive insect venom immunotherapy. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Side Effects (=Systemic Reaction, SR) During Venom Immunotherapy (VIT)	The primary objective of this study is to evaluate whether subjects under antihypertensive treatment with beta-blockers and/or angiotensin converting enzyme (ACE)-inhibitors show more side effects during VIT compared to subjects with no antihypertensive treatment.	after finishing the updosing phase (duration up to 6 months depending on the updosing protocol chosen by the patient) of a patient's venom immunotherapy; duration of Visit ~1hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Sting Reactions	To evaluate whether subjects under antihypertensive treatment with beta-blockers and/or ACE-inhibitors have more severe sting reactions.	duration of first visit (~1hour)
Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Severe Systemic Sting Reactions.	To correlate the prevalence of cardiovascular diseases and/or hypertension with the risk for more severe systemic sting reactions.	duration of first visit (~1hour)
Association of Bee Venom With a Higher Frequency of Side-effects (=Systemic Reaction, SR).	To evaluate whether bee venom is associated with a higher frequency of side-effects.	after finishing the updosing phase (duration up to 6 months depending on the updosing protocol chosen by the patient) of a patient's venom immunotherapy; duration of Visit ~1hour
Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR).	To evaluate whether high specific immunoglobulin E (sIgE) levels are correlated to a higher frequency of side-effects. sIgE levels are expressed in kilo units/liter [kU/L].	after finishing the updosing phase (duration up to 6 months depending on the updosing protocol chosen by the patient) of a patient's venom immunotherapy; duration of Visit ~1hour
Correlation of High Tryptase Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR).	To evaluate whether high tryptase levels are correlated to a higher frequency of side-effects	after finishing the updosing phase (duration up to 6 months depending on the updosing protocol chosen by the patient) of a patient's venom immunotherapy; duration of Visit ~1hour
Correlation of Quicker Up-dosing Protocols to a Higher Frequency of Side-effects (=Systemic Reaction, SR).	To evaluate whether quicker up-dosing protocols are correlated to a higher frequency of side-effects.	depends on the protocol used for venom immunotherapy, a maximum of about 6 months
Efficacy of VIT	The outcome (systemic reaction to sting or not) of sting challenges and/or field stings will be recorded to identify patients who will not tolerate but react to future stings. These results will be compared between patients not taking antihypertensive (AHT) drugs and patients taking AHT drugs.	1 year after reaching the maintenance dose; duration of Visit ~1hour
Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Frequent Side Effects (=Systemic Reaction, SR) Under VIT.	To correlate the prevalence of cardiovascular diseases and/or hypertension with the risk for more frequent side effects (=systemic reaction, SR) under VIT..	duration of Visit ~1hour

Collaborators and Investigators

• Sponsor: Medical University of Graz

Publications and helpful links

General Publications

• Sturm GJ, Herzog SA, Aberer W, Alfaya Arias T, Antolin-Amerigo D, Bonadonna P, Boni E, Bozek A, Chelminska M, Ernst B, Frelih N, Gawlik R, Gelincik A, Hawranek T, Hoetzenecker W, Jimenez Blanco A, Kita K, Kendirlinan R, Kosnik M, Laipold K, Lang R, Marchi F, Mauro M, Nittner-Marszalska M, Poziomkowska-Gesicka I, Pravettoni V, Preziosi D, Quercia O, Reider N, Rosiek-Biegus M, Ruiz-Leon B, Schrautzer C, Serrano P, Sin A, Sin BA, Stoevesandt J, Trautmann A, Vachova M, Arzt-Gradwohl L. beta-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy. Allergy. 2021 Jul;76(7):2166-2176. doi: 10.1111/all.14785. Epub 2021 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Anaphylaxis
• Other Study ID Numbers: 26-422 ex13/14 (EADOAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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