Allergic ReactionNCT06065137

Standardised Drug Provocation Testing in Perioperative Hypersensitivity

A study testing Full dose DPT with propofol, Full dose DPT with ketamine and Full dose DPT with etomidate in people with Allergic Reaction and Hypersensitivity, run by University Hospital, Antwerp at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The goal of this clinical trial is to evaluate the safety and outcome of systematic drug provocation testing with anaesthetics at therapeutic doses in adult patients undergoing diagnostic work-up for perioperative hypersensitivity. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Allergic Reaction, Hypersensitivity, Perioperative Complication
What is being tested?: Full dose DPT with propofol, Full dose DPT with ketamine and Full dose DPT with etomidate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteBelgium
Study dates: 23 Oct 2023to 30 Jun 2025
Phase: Interventional

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

patients consulting the allergology department of the Antwerp University hospital medical with a history consistent with perioperative hypersensitivity
Indication for diagnostic work-up as determined at an interdisciplinary meeting between allergologists and anaesthetists
willing to sign separate informed consent forms for both general anaesthesia and the Drug Provocation Test.

Who cannot join

patient refusal
incomplete diagnostic work-up
history inconsistent with perioperative hypersensitivity

Trial locations and contacts

1 site in 1 country.

Belgium1 site

Antwerp University Hospital
Edegem, Antwerp, 2650

Other trials in Belgium

About this study

Read the detailed description

Perioperative hypersensitivity reactions (POH) pose a risk for major morbidity and mortality in the perioperative period. After resolution of the initial reaction it is crucial to determine the culprit drug to allow safe anaesthetics for future procedures.However this is not easy, as many drugs are administered near simultaneously and both anaesthesia and surgery may provoke or mask many of the symptoms of a hypersensitivity reaction. Conventional testing seems to offer good predictive value based on the low incidence of POH in subsequent re-exposures after negative work-up. Despite negative work-up anaesthetists often chose not to re-administer an neuromuscular blocking agent (NMBA) used in the index reaction, especially if no other culprit was found. This introduces an important bias as this group (no culprit found, NMBA not re-exposed) might be at the highest risk of containing false negatives as NMBA are the most frequent cause of POH in our region.The same remark can be made regarding earlier attempts by our group and others at establishing the negative predictive value (NPV) of conventional testing through retrospective analysis of subsequent re-exposures.To truly establish the NPV for conventional testing and thus the need for DPT, a prospective approach is needed where all patients are challenged with index drugs after negative conventional testing.

Adult patients that are referred for diagnostic work-up for POH will be included if they have a clinical history fitting with POH.

All patients will first receive a full diagnostic work-up for all index products consisting of in vivo (skin tests) and in vitro (specific IgE and -for drugs in which it is available- basophil activation tests). Clinical reactions (both index reactions and any reactions during DPT) will be classified according to the National Audit Program (NAP-6) classification which separates non-fatal POH in 4 grades:

NAP 1 (only cutaneous/mucosal signs)
NAP 2 (circulatory or respiratory symptoms which don't require treatment)
NAP 3 (circulatory or respiratory symptoms which require treatment or potential airway compromise)
NAP 4 (fulfilling indications for cardiopulmonary resuscitation)

Skin tests will be performed at the allergology day clinic following the protocols of the French Society for Anaesthesia and Intensive Care and the French Society of Allergology. Based on these results we make a distinction between patients with an identified culprit and those without an identified culprit.

If a culprit has been found, all other index drugs are challenged at therapeutic doses. The standard testing is performed for alternatives for the culprit drug in the same drug class (such as NMBA) and one drug from this class that tests negative is also used in a challenge at a therapeutic dose.

If no culprit has been found after the initial work-up of skin tests and in vitro tests the next step is determined by the severity of the initial reaction. In NAP-6 grade 1-3 reactions all index drugs are challenged at therapeutic doses. As the benefits of DPT have yet to be fully quantified the risk-benefit analysis in the most severe reactions (NAP 4) is difficult to make. Hence, we use an 'confirmation by elimination' principle in these cases in which we only challenge with the drugs that do not carry the highest likelihood of being the culprit. This likelihood is based on both timing and epidemiology as NMBA are a much more common cause of POH in our region than all other anaesthetics combined. By eliminating all other drugs we 'clear' them for future use and gain confidence in our suspicion of the most likely culprit without having to administer them in this population.

Conditions: Allergic Reaction, Hypersensitivity, Perioperative Complication, Anaphylaxis, Anaphylactic Reaction, Immediate Hypersensitivity
Being tested: Full dose DPT with propofol, Full dose DPT with ketamine, Full dose DPT with etomidate, Full dose DPT with midazolam, Full dose DPT with fentanyl
Medical subject headings: Hypersensitivity, Anaphylaxis, Hypersensitivity, Immediate, Drug Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Full dose DPT with propofolDiagnostic test
Incremental administration of propofol up to a cummulative full therapeutic dose (2mg/kg) in POH patients investigated for propofol. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.02mg/kg-0.2 mg/kg -0.6 mg/kg -1.2mg/kg).
Full dose DPT with ketamineDiagnostic test
Incremental administration of ketamine up to a cummulative full therapeutic dose (1mg/kg) in POH patients investigated for ketamine. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.01 mg/kg -0.1 mg/kg -0.3 mg/kg -0.6mg/kg).
Full dose DPT with etomidateDiagnostic test
Incremental administration of etomidate up to a cummulative full therapeutic dose (0.2mg/kg) in POH patients investigated for etomidate. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.002 mg/kg -0.02 mg/kg -0.06 mg/kg -1.2mg/kg).
Full dose DPT with midazolamDiagnostic test
Incremental administration of midazolam up to a cummulative full therapeutic dose (0.05mg/kg) in POH patients investigated for midazolam. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.0005 mg/kg -0.005 mg/kg -0.015 mg/kg -0.03mg/kg).
Full dose DPT with fentanylDiagnostic test
Incremental administration of fentanyl up to a cummulative full therapeutic dose (1mcg/kg) in POH patients investigated for fentanyl. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.01 mcg/kg -0.1 mcg/kg -0.3 mcg/kg -0.6mcg/kg).
Full dose DPT with sufentanylDiagnostic test
Incremental administration of sufentanyl up to a cummulative full therapeutic dose (0.1mcg/kg) in POH patients investigated for sufentanyl. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.001 mcg/kg -0.01 mcg/kg -0.03 mcg/kg -0.06µg/kg).
Full dose DPT with alfentanilDiagnostic test
Incremental administration of alfentanil up to a cummulative full therapeutic dose (10mcg/kg) in POH patients investigated for alfentanil. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.1 mcg/kg -1 mcg/kg -3 mcg/kg -6µg/kg).
Full dose DPT with remifentanilDiagnostic test
Incremental administration of remifentanil up to a cummulative full therapeutic dose (0.5mcg/kg) in POH patients investigated for remifentanil. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.005 mcg/kg -0.05 mcg/kg -0.15 mcg/kg -0.3µg/kg).
Full dose DPT with rocuroniumDiagnostic test
Incremental administration of rocuronium up to a cummulative full therapeutic dose (0.6mg/kg) in POH patients investigated for rocuronium. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.006 mg/kg -0.06 mg/kg ). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.18 mg/kg -0.42mg/kg) are administerd under general anesthesia.
Full dose DPT with atracuriumDiagnostic test
Incremental administration of atracurium up to a cummulative full therapeutic dose (0.5mg/kg) in POH patients investigated for atracurium. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.005 mg/kg -0.05 mg/kg ). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.15 mg/kg -0.35mg/kg) are administered under general anesthesia .
Full dose DPT with cisatracuriumDiagnostic test
Incremental administration of cisatracurium up to a cummulative full therapeutic dose (0.15mg/kg) in POH patients investigated for cisatracurium. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.0015 mg/kg -0.015 mg/kg ). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.045 mg/kg -0.105mg/kg) are administered under general anesthesia .
Full dose DPT with succinylcholineDiagnostic test
Incremental administration of succinylcholine up to a cummulative full therapeutic dose (1mg/kg) in POH patients investigated for succinylcholine. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.01 mg/kg -0.1 mg/kg). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.3 mg/kg -0.7mg/kg) are administered under general anesthesia.

Study groups in NCT06065137
Study group	Role	What they receive
POH patients	Experimental	incremental administration of investigated anesthetics up to full therapeutic dose in POH patients. Receives: Diagnostic Test: Full dose DPT with propofol; Diagnostic Test: Full dose DPT with ketamine; Diagnostic Test: Full dose DPT with etomidate; Diagnostic Test: Full dose DPT with midazolam; Diagnostic Test: Full dose DPT with fentanyl; Diagnostic Test: Full dose DPT with sufentanyl; Diagnostic Test: Full dose DPT with alfentanil; Diagnostic Test: Full dose DPT with remifentanil; Diagnostic Test: Full dose DPT with rocuronium; Diagnostic Test: Full dose DPT with atracurium; Diagnostic Test: Full dose DPT with cisatracurium; Diagnostic Test: Full dose DPT with succinylcholine

What is being measured

The primary outcome is the main question the study is designed to answer.

Hypersensitivity during DPT
Prevalence of hypersensitivity during direct provocation for drugs that tested negatively in conventional tests.
Measured: 1 hour

Secondary outcomes (3)

Severe reactions during DPT
Prevalence of severe (NAP 3-4) hypersensitivity reactions during direct provocation testing
Measured: 1 hour
Adverse events during DPT
Prevalence of adverse events during or after direct provocation testing
Measured: 1 hour
Sensitivity of conventional tests
Sensitivity of skin tests, specific IgE and basophil activation tests for anaesthetics
Measured: 1 hour

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Oct 202330 Jun 2025

First posted3 Oct 2023
Study start23 Oct 2023
Primary completion30 Jun 2025
Study completion30 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Allergic ReactionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06065137
Sponsor's protocol ID: 2023-5451
Other IDs: 3265
Status last verified: Aug 2025
First submitted: 19 Sep 2023
Last updated: 8 Sep 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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