Antihypertensive Treatment, Hymenoptera Venom Allergy
Conditions
Brief summary
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.
Interventions
DRUGInsect 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.
Sponsors
Medical University of Graz
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Side Effects (=Systemic Reaction, SR) During Venom Immunotherapy (VIT) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Severe Systemic Sting Reactions. | duration of first visit (~1hour) | To correlate the prevalence of cardiovascular diseases and/or hypertension with the risk for more severe systemic sting reactions. |
| Association of Bee Venom With a Higher Frequency of Side-effects (=Systemic Reaction, SR). | 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 | To evaluate whether bee venom is associated with a higher frequency of side-effects. |
| Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | 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 | 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 \[kU/L\]. |
| Severity of Sting Reactions | duration of first visit (~1hour) | To evaluate whether subjects under antihypertensive treatment with beta-blockers and/or ACE-inhibitors have more severe sting reactions. |
| Correlation of Quicker Up-dosing Protocols to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | depends on the protocol used for venom immunotherapy, a maximum of about 6 months | To evaluate whether quicker up-dosing protocols are correlated to a higher frequency of side-effects. |
| Efficacy of VIT | 1 year after reaching the maintenance dose; duration of Visit ~1hour | 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. |
| Correlation of 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 | To correlate the prevalence of cardiovascular diseases and/or hypertension with the risk for more frequent side effects (=systemic reaction, SR) under VIT.. |
| Correlation of High Tryptase Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | 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 | To evaluate whether high tryptase levels are correlated to a higher frequency of side-effects |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 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 reaction and 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.
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. | 1,425 |
| Total | 1,425 |
Baseline characteristics
| Characteristic | Patients With a History of an Anaphylactic Sting Reaction | — |
|---|---|---|
| Age, Continuous | 52 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 810 Participants | — |
| Sex: Female, Male Male | 615 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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.
Time frame: 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
Population: 1342 patients underwent VIT and performed Visit 2. Of these 1342 patients, 93 experienced a systemic side effect during the updosing phase of VIT. Data were missing for 10 participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Frequency of Side Effects (=Systemic Reaction, SR) During Venom Immunotherapy (VIT) | number of patients with SR with AHT treatment | 19 Participants |
| Patients Who Underwent VIT Updosing | Frequency of Side Effects (=Systemic Reaction, SR) During Venom Immunotherapy (VIT) | number of patients with SR without AHT treatment | 74 Participants |
Comparison: It was assumed that 24% of the patients would be on β-blockers and/or ACE inhibitors (ACEI). A χ2 test with a two-sided 5% significance level has an 80% power to detect the difference between the group without antihypertensive medication with 6% SR during VIT and the group on β-blockers and/or ACEI with 12.3% SR during VIT (OR = 2.2) when the sample sizes are 631 and 200, respectively. A drop-out rate of 37% was assumed which resulted in a required number of 1,319 patients.p-value: 0.25Mixed Models Analysis
Secondary
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.
Time frame: 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
Population: 1342 patients underwent VIT and performed Visit 2. Of these 1342 patients, 93 experienced a systemic side effect during the updosing phase of VIT. Data missing for 10 participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Association of Bee Venom With a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR in patients treated with bee venom | 54 Participants |
| Patients Who Underwent VIT Updosing | Association of Bee Venom With a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR in patients treated with vespid venom | 39 Participants |
p-value: <0.001Mixed Models Analysis
Secondary
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 \[kU/L\].
Time frame: 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
Population: 1342 patients underwent VIT and performed Visit 2. Of these 1342 patients, 93 experienced a systemic side effect during the updosing phase of VIT. sIgE levels were only available for 1009 patients, the other data (=333) are missing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR, bee venom, IgE >0.35-3.5 kU/L | 17 Participants |
| Patients Who Underwent VIT Updosing | Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR, bee venom, IgE >3.5-17.5 kU/L | 17 Participants |
| Patients Who Underwent VIT Updosing | Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR, bee venom, IgE >17.5 kU/L | 8 Participants |
| Patients Who Underwent VIT Updosing | Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR, vespid venom, IgE >0.35-3.5 kU/L | 17 Participants |
| Patients Who Underwent VIT Updosing | Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR, vespid venom, IgE >3.5-17.5 kU/L | 9 Participants |
| Patients Who Underwent VIT Updosing | Correlation of High Specific Immunoglobulin E (sIgE) Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR, vespid venom, IgE >17.5 kU/L | 4 Participants |
Comparison: Analysis for sIgE levels - bee venom.p-value: 0.99Mixed Models Analysis
Comparison: Analysis for sIgE levels - vespid venom.p-value: 0.15Mixed Models Analysis
Secondary
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
Time frame: 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
Population: 1342 patients underwent VIT and performed Visit 2. Of these 1342 patients, 93 experienced a systemic side effect during the updosing phase of VIT. Tryptase levels were only available for 1204 patients. Data missing for 138 participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Correlation of High Tryptase Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR in patients with tryptase <11.4µg/L | 74 Participants |
| Patients Who Underwent VIT Updosing | Correlation of High Tryptase Levels to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR in patients with tryptase >11.4µg/L | 13 Participants |
p-value: 0.16Mixed Models Analysis
Secondary
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.
Time frame: depends on the protocol used for venom immunotherapy, a maximum of about 6 months
Population: 1342 patients underwent VIT and performed Visit 2. Of these 1342 patients, 93 experienced a systemic side effect during the updosing phase of VIT. Data concerning the updosing protocol used were available for 1321 patients; data missing for 21 participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Correlation of Quicker Up-dosing Protocols to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR in patients with conventional updosing | 5 Participants |
| Patients Who Underwent VIT Updosing | Correlation of Quicker Up-dosing Protocols to a Higher Frequency of Side-effects (=Systemic Reaction, SR). | SR in patients with quicker updosing | 84 Participants |
p-value: 0.5Mixed Models Analysis
Secondary
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..
Time frame: duration of Visit ~1hour
Population: Correlation cardiovascular disease with risk of more frequent side effects under VIT: 93 of 1342 patients (Visit 2) experienced a SR. Datasets missing:17
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Frequent Side Effects (=Systemic Reaction, SR) Under VIT. | systemic side-effect, cardiovascular disease | 30 Participants |
| Patients Who Underwent VIT Updosing | Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Frequent Side Effects (=Systemic Reaction, SR) Under VIT. | systemic side-effect, no cardiovascular disease | 63 Participants |
Comparison: Analysis for correlation of the prevalence of cardiovascular diseases and/or hypertension with the risk for more frequent SR under VIT.p-value: 0.11Mixed Models Analysis
Secondary
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.
Time frame: duration of first visit (~1hour)
Population: Correlation cardiovascular disease with risk of more severe systemic sting reaction: 601 of 1425 patients (Visit 1) experienced a severe systemic sting reaction. Datasets missing:9
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Severe Systemic Sting Reactions. | severe sting reaction, cardiovascular disease | 258 Participants |
| Patients Who Underwent VIT Updosing | Correlation of the Prevalence of Cardiovascular Diseases and/or Hypertension With the Risk for More Severe Systemic Sting Reactions. | severe sting reaction, no cardiovascular disease | 343 Participants |
Comparison: Analysis for correlation of the prevalence of cardiovascular diseases and/or hypertension with the risk for more severe systemic sting reactions.p-value: 0.04Mixed Models Analysis
Secondary
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.
Time frame: 1 year after reaching the maintenance dose; duration of Visit ~1hour
Population: Visit 3 was performed with 1186 patients one year after reaching the maintenance phase of VIT. Data missing for 4 participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Efficacy of VIT | SR after sting, AHT treatment | 4 Participants |
| Patients Who Underwent VIT Updosing | Efficacy of VIT | SR after sting, no AHT treatment | 15 Participants |
p-value: 0.72Fisher Exact
Secondary
Severity of Sting Reactions
To evaluate whether subjects under antihypertensive treatment with beta-blockers and/or ACE-inhibitors have more severe sting reactions.
Time frame: duration of first visit (~1hour)
Population: 1425 patients were included in the study at Visit 1. Of these 1425 patients, 603 initially experienced a severe (=Grade 3 and 4 according to the classification of Ring and Messmer), systemic sting reaction. Data were missing for 2 participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Who Underwent VIT Updosing | Severity of Sting Reactions | severe reactions in patients with AHT treatment | 171 Participants |
| Patients Who Underwent VIT Updosing | Severity of Sting Reactions | severe reactions in patients without AHT treatment | 432 Participants |
p-value: 0.29Mixed Models Analysis