Trial Outcomes & Findings for The Effect of Antihypertensive Drugs on Severity of Anaphylaxis and Side-effects During Venom Immunotherapy (NCT NCT04269629)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

1425 participants

Primary outcome timeframe

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

Results posted on

2020-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	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 reactions 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.
Overall Study STARTED	1425
Overall Study Number of Patients Who Performed VIT	1342
Overall Study COMPLETED	1186
Overall Study NOT COMPLETED	239

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With a History of an Anaphylactic Sting Reaction n=1425 Participants 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.
Age, Continuous	52 years n=1425 Participants
Sex: Female, Male Female	810 Participants n=1425 Participants
Sex: Female, Male Male	615 Participants n=1425 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1332 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
Frequency of Side Effects (=Systemic Reaction, SR) During Venom Immunotherapy (VIT) number of patients with SR with AHT treatment	19 Participants
Frequency of Side Effects (=Systemic Reaction, SR) During Venom Immunotherapy (VIT) number of patients with SR without AHT treatment	74 Participants

SECONDARY outcome

Timeframe: 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.

To evaluate whether subjects under antihypertensive treatment with beta-blockers and/or ACE-inhibitors have more severe sting reactions.

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1423 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
Severity of Sting Reactions severe reactions in patients with AHT treatment	171 Participants
Severity of Sting Reactions severe reactions in patients without AHT treatment	432 Participants

SECONDARY outcome

Timeframe: 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

To correlate the prevalence of cardiovascular diseases and/or hypertension with the risk for more severe systemic sting reactions.

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1416 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
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
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

SECONDARY outcome

Timeframe: 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.

To evaluate whether bee venom is associated with a higher frequency of side-effects.

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1332 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
Association of Bee Venom With a Higher Frequency of Side-effects (=Systemic Reaction, SR). SR in patients treated with bee venom	54 Participants
Association of Bee Venom With a Higher Frequency of Side-effects (=Systemic Reaction, SR). SR in patients treated with vespid venom	39 Participants

SECONDARY outcome

Timeframe: 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.

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 \[kU/L\].

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1009 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
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
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
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
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
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
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

SECONDARY outcome

Timeframe: 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.

To evaluate whether high tryptase levels are correlated to a higher frequency of side-effects

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1204 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
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
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

SECONDARY outcome

Timeframe: 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.

To evaluate whether quicker up-dosing protocols are correlated to a higher frequency of side-effects.

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1321 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
Correlation of Quicker Up-dosing Protocols to a Higher Frequency of Side-effects (=Systemic Reaction, SR). SR in patients with conventional updosing	5 Participants
Correlation of Quicker Up-dosing Protocols to a Higher Frequency of Side-effects (=Systemic Reaction, SR). SR in patients with quicker updosing	84 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1182 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
Efficacy of VIT SR after sting, AHT treatment	4 Participants
Efficacy of VIT SR after sting, no AHT treatment	15 Participants

SECONDARY outcome

Timeframe: 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

To correlate the prevalence of cardiovascular diseases and/or hypertension with the risk for more frequent side effects (=systemic reaction, SR) under VIT..

Outcome measures

Outcome measures
Measure	Patients Who Underwent VIT Updosing n=1325 Participants 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 and SR and changes in diseases and medication will be recorded. The frequency of systemic side-effects is recorded and compared between patients under antihypertensive treatment and patients not taking antihypertensive drugs.
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
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

Adverse Events

Patients With a History of an Anaphylactic Sting Reaction

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Assoz.-Prof. Dr. Gunter Sturm

Department of Dermatology and Venerology

Phone: +4331638580318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place